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Biochemistry
FA complete review
| Question | Answer |
|---|---|
| What is the condensed form of DNA called? | Chromatin |
| Which histone is termed the "linker"? | H1 |
| What gives DNA its negative charge? | Phosphate groups |
| What amino acids give histones its positive charge? | Lysine and arginine |
| What is the overall charge of DNA? | Negative |
| What is the charge of histones? | Positive |
| Which histone is not part of the nucleosome? | H1 |
| What are the histones that form the Nucleosome? | H2A, H2B, H3, and H4 (x2) |
| What is an Nucleosome? | Histone octamer surrounded by DNA |
| What is the relation between DNA and a Nucleosome? | DNA loops twice around a histone octamer to form an nucleosome. |
| In which phase is DNA and histone synthesized? | S-phase |
| What happens to DNA during mitosis? | DNA condenses to form chromosomes |
| What is unique about mitochondria in respect to DNA content? | It has its own DNA, which is circular and does not utilize histones |
| Which is the form of condensed chromatin? | Heterochromatin |
| What form of chromatin is transcriptionally inactive and sterically inaccessible? | Heterochromatin |
| Which form of chromatin features an increase in methylation and decrease in acetylation? | Heterochromatin |
| Highly condensed chromatin | Heterochromatin |
| What are Barr bodies? | Inactive X chromosomes |
| Where are Barr bodies usually found? | Periphery of nucleus |
| Which form chromatin appears lighter on EM? | Euchromatin |
| Euchromatin is: | Transcriptionally active and sterically accessible |
| What is does DNA methylation accomplishes? | Changes the expression of DNA segment without changing the sequence |
| What are some situations in which there is DNA methylation involvement? | -Genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis |
| The process of aging is associated with DNA ___________. | Methylation |
| What happens in case of methylation within gene promoter? | Represses gene transcription |
| What are CpG sites? | Regions of DNA where cytosine nucleotide is followed by guanine nucleotide along the linear sequence of bases in the 5'--> 3' direction |
| What happens in Histone methylation? | Reversible transcriptional suppression, but can also cause activation depending on location of methyl groups |
| Mute DNA is produced by which process? | Histone methylation |
| What process causes the relaxation of DNA coiling, allowing for transcription? | Histone acetylation |
| What process makes DNA active? | Histone acetylation |
| What is the compositional difference between a nucleoside and a Nucleotide? | Nucleoside has an added Sugar, while a nucleotide has an added phosphate |
| Base + (deoxy)ribose + phosphate = | Nucleotide |
| What links together the phosphate in a nucleotide? | 3'-5' phosphodiester bond |
| How many rings are in the Purine structure? | 2 |
| A nucleotide with one ring only is a _____________________. | Pyrimidine |
| Which are the two Purines? | Guanine and Adenine |
| Which are the 3 Pyrimidines? | Cytosine, Uracil, and Thiamine |
| Uracil is found in __________. | RNA |
| Thymine is found in ________________. | DNA |
| The methylation of uracil makes ____________. | Thymine |
| What is the added group to thymine, that differs it form Uracil? | Methyl group |
| Which nucleotides for a 3 H bond? | G === C |
| A--T bond has _____ H bonds. | 2 |
| What type of bonds are responsible for increasing the melting point of DNA? | G === C |
| What amino acids are necessary to create Purines? | Glycine, Aspartate, and Glutamine |
| List of drugs that interfere or prevent Pyrimidine synthesis? | -Leflunomide -Methotrexate (MTX), trimethoprim (TMP), and Pyrimethamine - 5- fluorouracil (5-FU) |
| Leflunomide inhibits which enzyme? | dihydroorotate dehydrogenase |
| What components are needed the de novo purine salvage pathway? | Aspartate, glycine, glutamine, and THF |
| What enzyme is inhibited by MTX? | Dihydrofolate reductase |
| A decrease of dTMP in humans is commonly due to use of: | MTX and/or 5-FU |
| What drug is used to inhibit dihydrofolate reductase in bacteria? | TMP |
| What type of dihydrofolate reductase inhibitor is used in Protozoan infections? | Pyrimethamine |
| Which enzyme is inhibited by 5-FU? | Thymidylate synthase |
| What is a common Thymidylate synthase inhibitor? | 5-FU |
| What are 3 common drugs that inhibit Purine synthesis? | - 6-mercaptopurine (6-MP), - Mycophenolate and Ribavirin |
| What is the prodrug of 6-MP? | Azathioprine |
| Azathioprine inhibits the ___________. | de novo purine synthesis |
| What enzyme is inhibited by Mycophenolate and by Ribavirin? | Inosine monophosphate dehydrogenase |
| Enzyme inhibited by Hydroxyurea? | Ribonucleotide reductase |
| Drug that inhibits both, Purine and Pyrimidine, synthesis? | Hydroxyurea |
| CPS2 is used in the ____. | Cytosol |
| What are characteristics shared by Eukaryotic and Prokaryotic DNA replication? | - Semiconservative (involves both continuous and discontinuous synthesis) - Occurs in the 5' ---> 3' direction |
| What is the direction of DNA replication? | 5' -----> 3' |
| What are the name of the discontinuous fragments of DNA replication? | Okazaki fragments |
| What is the Origin of Replication? | Particular consensus sequence of base pairs in genome where DNA replication begins |
| Which type of DNA replication depicts multiple origins of replication? | Eukaryote |
| How many origins of replication are seen in Prokaryotic DNA replication? | Single (one) |
| What would a AT-rich sequence in DNA indicate? | Areas of promoters and origins of replication |
| What is an example of a popular AT-rice sequence area? | TATA box regions |
| What is the Replication fork? | Y-shaped region along DNA template where leading and lagging strands are synthesized |
| What is the role of Helicase? | Unwinds DNA template at replication fork |
| Where does the Helicase work? | Replication Fork |
| What is the role of Single-stranded binding proteins? | Prevent strands from reannealing |
| What prevents DNA strands (leading and lagging) in DNA replication form annealing before time? | Single-stranded binding proteins |
| What is the function of DNA topoisomerases? | Create a single or double-stranded break in the helix to add or remove supercoils |
| What proteins are used to add or remove supercoils in DNA helix at moment of DNA replication? | DNA Topoisomerases |
| In Eukaryotes, TOP I is inhibited by which drugs? | Irinotecan/Topotecan |
| TOP II in eukaryotes is inhibited by: | Etoposide/Teniposide |
| Etoposide inhibits: | Topoisomerase II (TOP II) in eukaryotes cells. |
| Which type of cells do fluoroquinolones work? | Prokaryotes |
| Which TOPs are inhibited by fluoroquinolones? | II and IV |
| What is a common name for Prokaryotic TOP II? | DNA gyrase |
| What is the function of Primase? | Makes an RNA primer on which DNA polymerase III can initiate replication |
| Which DNA pol work on RNA primer to start replication? | III |
| DNA Pol III is found in ____________________ only. | Prokaryotic |
| Which DNA polymerases are only found in Prokaryotic organisms? | I and III |
| What is the role of DNA pol III in the prokaryotic leading strand? | Elongation by adding deoxynucleotides to the 3' end |
| The elongation of the lagging strand by DNA pol III is stopt as it reaches the _____________. | Primer |
| What is a key characteristic of DNA pol III? | 3' ---> 5' exonuclease activity "proofreads" each added nucleotide |
| What is the direction of DNA pol III synthesis? | 5' --> 3' |
| What is the direction of DNA Pol III proofreading activity? | 3' ---> 5' |
| What is the purpose of drugs having a modified 3' OH? | Prevent the addition of the next nucleotide by DNA pol III |
| What is the function of DNA pol I? | Degrades RNA primer; replaces it with DNA |
| How is the RNA primer excised? | By DNA pol I with 5' --> 3" exonuclease activity |
| What is the function of DNA ligase? | Catalyzes the formation of phosphodiester bond within a strand of dsDNA |
| What protein is in charge of joining Okazaki fragments? | DNA ligase |
| Telomerase is found in ___________ only. | Eukaryotes |
| What is and the function of Telomerase? | Reverse transcriptase that adds DNA to 3' ends of chromosomes to avoid genetic material with every duplication |
| What compound prevents the loss of genetic material everytime a duplication occurs? | Telomerase |
| Which enzyme is often dysregulated and allows cancer cells to have unregulated replication? | Telomerase |
| How is the reverse transcriptase of Telomerase? | RNA-dependent DNA polymerase |
| What is the added DNA by Telomerase reverse transcriptase? | TTAGGG |
| To which end of DNA do Telomerase add the new DNA ? | 3' end |
| What type of mutation of DNA is the most severe? | Frameshift |
| What is more severe, a missense or an nonse mutation of DNA? | Nonsense |
| What kind of DNA mutation is the least severe? | Silent |
| What is a Transition DNA mutation? | Change from a Purine to a purine (or Pyrimidine to Pyrimidine) |
| A DNA mutation the converts a Purine into a Pyrimidine (or vice versa) is known as: | Transversion |
| Nucleotide substitution but codes for the same amino acid. | Silent mutation |
| What is the base change MC seen in a silent mutation? | 3rd base |
| What is tRNA wobble? | Base change in 3rd position of codon |
| Very common disease due to a Missense mutation? | Sickle cell disease |
| What is the mutation seen in Sickle cell disease? | Missense |
| Substitution of Glutamic acid with valine. Dx? | Sickle cell disease |
| Missense mutation definition? | Nucleotide substitution resulting in changed amino acid |
| When is a missense mutation referred as conservative? | If new amino acid is similar in chemical structure |
| What amino acid replaces glutamic acid in Sickle cell disease? | Valine |
| What kind of mutation results in the premature appearance of a Stop codon? | Nonsense |
| What are the Stop Codons? | UAG, UAA, and UGA |
| What is the most common result of a nonsense DNA mutation? | Non-functional proteins |
| Two common condition due to a Frameshift mutation? | 1. Duchenne muscular dystrophy 2. Tay-Sachs disease |
| What is a Frameshift mutation? | Deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading all nucleotides downstream |
| A mutation at splice site causes: | 1. Retained intron in the mRNA ---> protein with impaired or altered function |
| What is often the cause of a retained intron in mRNA? | Mutation at the splice site |
| What form of Thalassemia is seen with a Splice site mutation? | B-thalassemia |
| B-thalassemia is commonly due to a _____________________ mutation. | Splice site |
| What is the lac operon? | Operon required for the transport and metabolism of lactose in E. coli and many other organisms |
| What the main microbial organism required of the lac operon? | E. coli |
| What is a classic example of response to an environmental change? | The use of lac operon in E. coli in the absence of glucose in the environment |
| What is activated in the metabolism of Lactose by E. coli? | Lac operon |
| What is the relation between lac operon, CAP and glucose level? | Low glucose induces the activation of CAP leading to increase transcription by lac operon in E. coli. |
| Which state creates a strong expression of lac genes? | Low glucose and lactose available |
| No glucose and no lactose available means ? | No lac genes expressed |
| Which level of glucose, low or high, induces or promotes lac gene expression? | Low glucose levels |
| What are the three types of Single strand DNA repairs? | 1. Nucleotide excision repair 2. Base excision repair 3. Mismatch repair |
| What is nucleotide excision repair? | Specific endonucleases release the oligonucleotides containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively. |
| Nucleotide excision repair occurs in what phase to the cell cycle? | Phase 1 |
| What is a common condition due to a defective Nucleotide excision repair? | Xeroderma pigmentosum |
| What is defective in Xeroderma pigmentosum? | The nucleotide excision repair is unable to repair DNA pyrimidine dimers caused by UV exposure. |
| What are some important findings of Xeroderma pigmentosum? | Dry skin, extreme light sensitivity, skin cancer |
| What is base excision repair? | Base-specific Glycosylase removes altered base and creates AP site |
| In which end of nucleotide does the AP-endonuclease work? | 5' endo |
| Unlike Nucleotide excision repair, the base excision repair occurs ___________________ of the cell cycle. | Throughout the entire |
| What DNA repair mechanism is especially important in spontaneous/toxic deamination? | Base excision repair |
| What is Mismatch repair? | Newly synthesized strand is recognized, mismatched nucleotides are removed, and the gap is filled an resealed. |
| What condition is due to a defective mismatch repair? | Lynch syndrome ( hereditary nonpolyposis colorectal cancer [NNPCC]) |
| Mismatch repair mainly occurs during which phase of the cell cycle? | S-phase |
| WHat are the two kinds of double strand DNA repair? | 1. Non-homologous end joining 2. Homologous recombination |
| What condition is seen with defective Non-homologous end joining? | Ataxia telangiectasia and Fanconi anemia |
| Defective Homologous recombination gives rise to: | Breast/Ovarian cancer with BRCA1 mutation |
| What is Nonhomologous end joining DNA repair? | The bringing together of 2 ends of DNA fragments to repair double-stranded breaks |
| Which kind of double stranded DNA repair does not require DNA homology? | Nonhomologous end joining |
| Requireds two homologous DNA duplexes | Homologous recombination |
| What describes homologous recombination? | A strand fro the damaged dsDNA is repaired using a complementary strand from the intact homologous dsDNA as a template |
| Which type of double stranded DNA repair does not loss any genetic material? | Homologous recombination |
| What is the mRNA start codon? | AUG |
| AUG is: | mRNA start codon |
| Describe the start codon (AUG) in eukaryotes. | Codes for methionine, which may be removed before translation is completed |
| AUG in eukaryotic cells code for? | Methionine |
| What does AUG codes in prokaryotic cells? | N-formylmethionine (fMet) |
| What is "fMet"? | The coding of UAG in prokaryotes |
| What is a alternate function of fMet? | Stimulation of neutrophil chemotaxis |
| Name the 3 stop codons: | 1. UGA 2. UAA 3. UAG |
| The promoter is on the _______ end of the gene. | 5' end |
| What makes up the promoter in Eukaryotic genes? | CAAT box and TATA box |
| AATAAA is? | Polyadenylation signal |
| Which end of the gene has the polyadenylation signal? | 3' end |
| What are the main factors or proteins involved in the regulation of gene expression? | Promoters, Enhancers, and Silencers |
| What is the promoter? | Site where RNA polymerase II and multiple other transcription factors bind to DNA upstream for gene locus |
| What is a common result from a promoter mutation? | Dramatic decrease in level of gene transcription |
| Sudden, severe decrease in level of transcription, it most commonly indicate? | Promoter mutation |
| Another name for an Enhancer? | Activator |
| What is the function of Enhancers? | DNA locus where regulatory proteins bind --> increasing expression of a gene on the the same chromosome |
| Which regulator of gene expression increases the expression? | Enhancer |
| DNA locus in which regulatory proteins bind and cause the decrease of gene expression on same chromosome? | Silencer |
| In base excision repair: | Only the damaged base is removed and repair the gap. |
| How many RNA polymerases are in Prokaryotes? | One RNA polymerase makes all 3 kinds of RNA |
| Which drug works by inhibiting DNA-dependent RNA polymerase in prokaryotes? | Rifampin |
| Rifampin works on: | Prokaryotic DNA-dependent RNA polymerase |
| How many types of RNA polymerases are in Eukaryotic organism? | 3 |
| What RNA pol makes rRNA in eukaryotic cell? | RNA pol I |
| What is the most common type of RNA in eukaryotic cells? | rRNA made by RNA pol I |
| Where is rRNA only found? | Nucleolus |
| What is the largest RNA, and most massive RNA in eukaryotic cells? | mRNA |
| Which RNA pol creates mRNA? | RNA pol II |
| In what direction is mRNA read? | 5' to 3' |
| What kind of RNA pol makes 5S rRNA, tRNA? | RNA pol III |
| What is common function of RNA polymerase II? | Opens DNA at proomter site |
| What substance can inhibit RNA pol II/ | a-amanitin |
| Where is a-amanitin found? | Amanita phalloides |
| Actinomycin D MOA? | Inhibits RNA polymerase in both prokaryotes and eukaryotes |
| In RNA processing (eukaryotic) what is the initial transcript? | Heterogenous nuclear RNA (hnRNA) |
| What are 3 important processes occur in the nucleus to RNA processing? | 1. Capping of 5' end 2. Polyadenylation of 3' end 3. Splicing out of introns |
| What occurs by Capping of 5' in RNA processing? | Addition of 7-methylguanosine cap |
| Capped, tailed, and sliced transcript refers to: | mRNA |
| Where is mRNA translated? | Cytosol |
| What is in charge of mRNA quality control? | P-bodies in the cytosol |
| P-bodies contain: | Exonucleases, decapping enzymes, and microRNAs, which all serve as mRNA quality control |
| AAUAAA = | Polyadenylation signal in RNA |
| What are important protein in the first step of Splicing of pre-mRNA? | Small nuclear ribonucleoproteins (snRNPs) |
| During splicing of pre-mRNA, which are taken out, Exons or Introns? | Intron |
| Which end of mRNA suffers the first cleavage during Splicing of introns? | 5' end |
| Which, exon or intron, contains genetic information coding for protein? | Exon |
| Intervening noncoding segments of DNA | Intron |
| What is "Alternative Splicing"? | Splicing that produces a variety of protein products from a single hmRNA sequence |
| What are examples of Alternative splicing? | Tropomyosin variantes in muscle, Dopamine receptors in the brain, Transmembrane vs secreted Ig |
| What is the result of variant splicing of Introns and Exons? | Implicati in oncogenesis and many genetic disorders |
| What are some examples of genetic disoders due to defective Splicing? | B-thalassemia, Gaucher disease, Tay-Sachs disease, Marfan syndrome |
| What are microRNA? | Small, conserved, noncoding RNA molecules that post transcriptional regulate gene expression by targeting the 3' untranslated regions of specific mRNAs for degradation or translational repression |
| What is the possible result of abnormal expression of microRNA? | Certain malignancies due silencing an mRNA form a tumor suppressor gene |
| What is the abbreviation for microRNA? | miRNA |
| What molecules target 3' untranslated region of specific mRNAs? | miRNA |
| What is the structure of tRNA? | 75-90 nucleotides, secondary structure, cloverleaf form, anticodon end opposite 3' aminoacyl end |
| What is found in all, prokaryotic and eukaryotic, tRNA 3' end? | CCA |
| An amino acid is covalently bound to the ______________ of the tRNA. | 3' end |
| What mnemonic is used to remember the CCA 3' end of tRNA? | Can Carry Amino acids |
| Where would an amino acid bind in the tRNA? | CCA 3' end |
| Where in the tRNA does a ribosome binds? | T-arm |
| What is the role or purpose of D-arm in tRNA? | Contains dihydrouridine residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase |
| What is the amino acid acceptor site of tRNA? | 5'- CCA-3' |
| What happens with a mischarged tRNA? | Reads usual codon but inserts wrong amino acid |
| What enzyme is in charge of properly charging the amino acid in the tRNA? | Aminoacyl-tRNA synthetase |
| How is the accuracy of amino acid selection properly regulated? | Aminoacyl-tRNA synthetase and boding of charged tRNA to the codon |
| What is another term for referring codon-anticodon? | Pairing |
| In tRNA translation the term charging refer to: | Aminoacylation |
| What is identified by Eukaryotic initiation factors (iEFs)? | The ' cap or an internal ribosome entry site |
| What is the composition of Eukaryotic ribosomes? | 40S + 60S = 80S |
| What is the composition of Prokaryotic ribosomes? | 30S +50S = 70S |
| What type of cells have an 80S ribosome? | Eukaryote |
| Which type of organism are found with 70S ribosomes? | Prokaryote |
| Synthesis of proteins in the ribosomes occurs form the ________ to the ____-terminus. | N- terminus -----> C - terminus |
| What causes the interaction of ATP and tRNA? | Activation (charging) |
| GPT and tRNA associated causes _____________________. | Translocation |
| What are the three steps involved in Protein synthesis? | Initiation --> Elongation --> Termination |
| What is the first step in the ELONGATION part of Protein synthesis? | Aminoacyl-tRNA binds to A site, which requires GTP. |
| What source of energy is required to accomplish the fist step of the Elongation process in protein synthesis? | GTP |
| Which is the only part which is not affected by the aminoacyl-tRNA binding to the A site? | Initiator methionine |
| The A site? | Incoming Aminoacyl-tRNA |
| The P site? | Accommodates growing peptide |
| The E site? | Holds Empty tRNA as it exists |
| What is the second step of elongation process? | rRNA catalyzes peptide bond formation, transfer growing polypeptide to amino acid in A site |
| What is the final and third step in the elongation process of Protein synthesis? | RIbosome advances 3 nucleotides toward 3' end of mRNA, moving peptidyl tRNA to P site |
| What is the termed used to describe the move of peptidyl tRNA to P site? | Translocation |
| Describe the Termination phase of Protein synthesis? | Release factor recognizes stop codon and halts translation --> completed polypeptide is released form ribosome |
| What are two important Post Translational modifications? | 1. Trimming 2. Covalent alterations |
| What is the post translational modification "Trimming"? | The removal of N- or C-terminal propeptides from zymogen to generate mature protein |
| The conversion of Trypsinogen to trypsin is an example of: | Trimming |
| What are the important Covalent alterations classified as Post Translational modifications? | Phosphorylation, glycosylation, hydroxylation, methylation, acetylation, and Ubiquitination |
| What is the main role a chaperone protein? | Facilitating and/or maintaining protein folding |
| What is the purpose of Checkpoints in the Cell cycle? | Control transitions between phases of cell cycle |
| What are the proteins involved in the regulation of the cell cycle? | Cyclins, cyclin-dependent kinases (CDKs), and tumor suppressors |
| Which is the shortest phase of the cell cycle? | M phase |
| What are the main two components or events of the M phase of the cell cycle? | Mitosis and Cytokinesis |
| What are the subdivisions that make up mitosis? | Prophase, Prometaphase, Metaphase, Anaphase, and Telophase |
| What are the cyclins? | Regulatory proteins that control cell cycle events |
| What is used to activate CDKs? | Cyclins |
| What is the role of Cyclin-CDK complexes? | Phosphorylate other proteins to coordinate cell cycle progression |
| What is the function of p53 and Rb tumor suppressors? | p53 induces p21, which inhibits CDKs --> hypophosphorylation of Rb --> inhibition of G1-S phase progression. |
| The hypophosphorylatoin of Rb means: | Activation of Rb |
| What is a common syndrome resulting from mutations in p53 tumor suppressor genes? | Li-Fraumeni syndrome |
| In the G1 to S phase transition growth factors bind to: | Tyrosine kinase receptors |
| What are some common growth factors that bind to Tyrosine kinase receptors? | Insulin, PDGF, EPO, EGF |
| What are examples of Permanent cell types? | Neurons, skeletal and cardiac muscle, RBCs |
| Remain in G 0, regenerate from stem cells | Permanent cells |
| Which are common examples of Stable cells? | Hepatocytes, lymphocytes, PCT, and Periosteal cells |
| What is another name of Stable cells? | Quiescent cells |
| Enter G1 from G0 when stimulated | Stable cells |
| What are the Labile cell examples: | Bone marrow, gut epithelium, skin, hair follicles, and germ cells |
| Never go to G0, divide with a short G1 | Labile cells |
| Which type of cells are the ones most affected by Chemotherapy? | Labile cells |
| What occurs in the Rough Endoplasmic Reticulum (RER)? | Site of synthesis of secretory proteins and of N-linked oligosaccharide addition to many proteins. |
| What are the two main events that occur in the RER? | 1. Synthesis of secretory proteins 2. N-linked oligosaccharide addition to many proteins |
| What is the Nissl bodies? | RER in neurons |
| What is the function of Nissl bodies? | Synthesize peptide neurotransmitters for secretion |
| What are the "free ribosomes"? | Unattached to any membrane; site of synthesis of cytosolic and organellar proteins |
| What are some common cells rich in RER? | 1. Mucus-secreting goblet cells of the small intestine 2. Antibody-secreting plasma cells |
| What is the function of Smooth endoplasmic reticulum (SER)? | Site of steroid synthesis and detoxification of drugs and poisons |
| Which type of endoplasmic reticulum lacks of surface ribosomes? | Smooth |
| Which are some common cells rich in SER? | 1. Liver hepatocytes 2. Steroid hormone-producing cells of the adrenal cortex and gonad |
| What is the function of the Golgi? | Distribution center for proteins and lipids form the ER to the vesicles and plasma membrane |
| What are important tagging actions in the Golgi? | 1. Modifies N-oligosaccharide on Asparagine 2. Adds O-oligosaccharide on serine and threonine 3. Adds mannose-6-phosphate to proteins for trafficking to lysosomes. |
| What are Endosomes? | Sorting centers for material from outside the cell or from the Golgi |
| What is the function of Endosomes? | Sending material from outside the cell or from the Golgi, to lysosomes for destruction or to the membrane/Golgi for further use |
| What is I-cell disease? | Inherited lysosomal storage disease |
| What is the cause of I cell disease? | Defect in N-acetylglucosaminyl-1-phosphotransferase --> failure of the Golgi to phosphorylate mannose residues on glycoproteins, which causes proteins to be secreted extracellularly instead going to lysosomes. |
| What organelle is defective or malfunctioning in I cell disease? | Golgi |
| What are the common features of I cell disease? | Coarse facial features, gingival hyperplasia, clouded corneas, restricted joint movements, claw hand deformity, kyphoscoliosis, and high plasma levels of lysosomal enzymes |
| Which specific residue is wrongly phosphorylated in I cell disease? | Mannose residues (decrease mannose-6-phosphate) |
| What is the Signal recognition particle (SRP)? | Abundan, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER |
| What is the result of absent or defective SRP? | Proteins accumulate in the cytosol |
| What are three common vesicular trafficking proteins? | COP I, COP II, and Clathrin |
| Which vesicular trafficking protein has retrograde movement? | COP I |
| Going from the cis-Golgi to the ER means: | Retrograde movement by COP I |
| Which protein helps the protein going anterograde fashion, from ER to the cis-Golgi? | COP II |
| What vesicular trafficking protein help the movement form the trans-Golgi to the Lysosomes? | Clathrin |
| What are the 4 main actions of a Peroxisome? | 1. Beta oxidation of very-long-chain fatty acids (VLCFA) 2. Alpha-oxidation 3. Catabolism of branched-chain fatty acids, amino acids, and ethanol 4. Synthesis of cholesterol, bile acids, and plasmalogens |
| What organelle is defective in Zellweger syndrome? | Peroxisome |
| Which action of a Peroxisome is strictly a peroxisomal process? | Alpha-oxidation |
| What is the inheritance form of Zellweger Syndrome? | Autosomal recessive |
| What is the cause of Zellweger syndrome? | Mutated PEX genes |
| Clinical features of a Zellweger syndrome patient? | Hypotonia, seizures, hepatomegaly, and early death |
| What are common pathological conditions of defective Peroxisome? | Zellweger syndrome, Refsum disease, and Adrenoleukodystrophy. |
| Which Peroxisomal diseases are of AR inheritance? | Zellweger syndrome and Refsum disease |
| X-linked recessive disorder of B-oxidation. Dx? | Adrenoleukodystrophy |
| What disease is caused by a defective alpha oxidation process? | Refsum disease |
| What is the result of defective alpha oxidation in Refsum disease? | Phytanic acid is not metabolised to pristanic acid |
| What is the clinical features of Refsum disease? | Scaly skin, ataxia, cataracts/night blindness, shortening of 4th toe, epiphyseal dysplasia |
| What condition is to be suspected in case of VLCFA buildup in adrenal glands, white matter of brain, and testes? | Adrenoleukodystrophy |
| What is the role/ function of Proteasome? | Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins |
| What are some implications in an defective ubiquitin-proteasome system? | Cases of Parkinson disease |
| A network of protein fibers within the cytoplasm that supports cell structure, cell and organelle movement, and cell division. | Cytoskeletal elements |
| What is the main function of Microfilaments? | Muscle contraction and cytokinesis |
| What are examples of microfilaments? | Actin, and microvilli |
| What is the function of Intermediate filaments? | Maintain cell structure |
| What are some examples of intermediate filaments? | Vementin, desmin, cytokeratin, lamins, glial fibrillary acidic protein (GFAP), and neurofilaments |
| Vimentin is: | Intermediate filament that works to maintain cell structure |
| Cytokeratin is an _______________________ filament. | Intermediate |
| What is the main function of microtubules? | Movement and cell division |
| What are some important examples of Microtubules? | Cilia, flagella, mitotic spindle, axonal trafficking, and centrioles |
| Description of outer structure of a microtubule. | Cylindrical; composed of array of polymerized heterodimers of a- and B-tubulin |
| What is bound to each dimer in a microtubule? | 2 GTP |
| What are Molecular motor proteins function? | Transport cellular cargo toward opposite ends of microtubule |
| What are the two most important molecular motor proteins? | Dynein and Kinesin |
| How is the transport of Dynein? | Retrograde to microtubule (+ --> -) |
| Anterograde to microtubule transport is done by ______________. | Kinesin |
| What are some drugs that act on microtubules? | 1. Mebendazole 2. Griseofulvin 3. Colchicine 4. Vincristine/Vinblastine 5. Paclitaxel |
| What are the anticancer medications that act on microtubules? | Vincristine/Vinblastine and Paclitaxel |
| Which anthelmintic MOA is on the microtubule structure? | Mebendazole |
| What antifungal is used to inhibit microtubule formation? | Griseofulvin |
| What structure is targeted in the use of Colchicine? | Microtubule |
| 9 doublet + 2 singlet arrangement of microtubules describe the structure of _______________. | Cilia |
| How is the basal body of cilia formed? | 9 microtubule triplets with no central microtubules |
| What is the function of Axonemal dynein? | ATPase that links peripheral 9 doublets and causes bending cilium by differential sliding of doublets |
| What structures enable coordinated ciliary movement? | Gap junctions |
| What is the cause of Kartagener syndrome? | Immotile cilia due to a dynein arm defect |
| What is another name for Kartagener syndrome? | Primary ciliary dyskinesia |
| What is the main reproductive affection of Kartagener in both, male and females? | Infertility |
| Why the infertility in males with Kartagener syndrome? | Immotile sperm |
| Dysfunctional fallopian tube cilia, leading to infertility is a common feature of _________________________ syndrome. | Kartagener syndrome |
| What are some clinical developments or features seen in Kartagener syndrome, besides infertility? | Bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss, and situs inversus |
| Dextrocardia on CXR. Suspect Dx? | Kartagener syndrome |
| The Na-K+ ATPase is located at: | Plasma membrane with ATP side on cytosolic side |
| In regards to the Sodium-Potassium pump, for every 3 Na+ that got out of ceh cell, how many K+ come into cell? | 2 |
| The exit or "pumped out" of 3 Na+ by the Na+K+ ATPase, is called: | Pump phosphorylated |
| When the Na+/K+ pump is referred as dephosphorylated, it indicates the: | 2K+ ions coming into the cell |
| Which cardiac glycoside MOA is to inhibit the binding of K+ to in the Na/K pump? | Ouabain |
| Which cardiac glycoside directly inhibit the Sodium Potassium pump? | Digoxin |
| What is the most abundant protein in the human body? | Collagen |
| What is the main function of Collagen? | Organizes and strengthens extracellular matrix |
| What type of collagen is the most common? | Type I |
| What condition is due to a defective type I collagen? | Osteogenesis imperfecta type I |
| What tissues are made of Type I collagen? | Bone, Skin, Tendon, dentin, fascia, cornea, and late wound repair |
| What tissues are of type II collagen? | Cartilage, vitreous body, and nucleus pulposus |
| What type of collagen makes up Reticulin- skin, blood vessels, uterus, fetal tissue, and granulation tissue? | Type III |
| What is made with type IV collagen? | Basement membrane, basal lamina, and lens |
| Which type of collagen is found in the cornea? | Type I |
| Cartilage is type ___ collagen. | II |
| Blood vessels type _____ collagen. | III |
| Bone, Skin, and tendon are of type ____ collagen. | I |
| What condition is associated to defective type 3 collagen? | Vascular type Ehlers-Danlos syndrome |
| Which type of Ehlers-Danlos syndrome is due to defective type III collagen? | Vascular |
| Type IV collagen is attacked by autoantibodies in which common condition? | Goodpasture syndrome |
| What pathology is seen with defictive Type IV collagen? | Alport syndrome |
| Which two disease are associated by defective/damaged Type IV collagen? | Alport syndrome and Goodpasture syndrome |
| If Collagen type IV is defective, it most likely refers to which condition? | Alport syndrome |
| Which is an autoimmune disease of collagen IV? | Goodpasture syndrome |
| What collagen IV structure is damaged in Alport syndrome? | Basement membrane |
| Where does synthesis of collagen occurs? | Rough Endoplasmic Reticulum |
| Which organelle contains preprocollagen accumulation? | Rough Endoplasmic Reticulum |
| Gly-X-Y (X and Y are proline or lysine). | Preprocollagen |
| What is the best approximate fraction of Glycine content in preprocollagen? | 1/3 |
| In Collagen synthesis which is the order in which reaction occurs FIRST, hydroxylation or glycosylation? | Hydroxylation occurs first |
| What is required in order for Hydroxylation of collagen in the RER to occur? | Vitamin C |
| What is scurvy? | Vitamin C deficiency |
| A person with vitamin C deficiency will have an impaired __________ step in the synthesis of collagen. | Hydroxylation |
| What is hydrolyzed in the hydroxylation step of Collagen synthesis? | Proline and Lysine residues |
| What happens in the Glycosylation of collagen synthesis pathway? | Glycosylation of pro-a-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds |
| What premature form of collagen is produced by Glycosylation step? | Procollagen |
| What step in collagen synthesis produces the triple helix of 3 collagen a-chains? | Glycosylation |
| Problems forming the triple helix result in development of: | Osteogenesis imperfecta |
| Specifically, Osteogenesis imperfecta is due to a defective ___________________ step in collagen synthesis. | Glycosylation |
| What form of collagen is exocytosed into extracellular space? | Procollagen |
| Defective cleavage of Procollagen leads to development of _____________________ syndrome. | Ehlers-Danlos |
| What is form by the cleavage of disulfide-rich terminal regions of procollagen? | Insoluble tropocollagen |
| What are two disease associated with improper collagen cross linking? | Ehlers-Danlos syndrome and Menkes Disease |
| What is the enzyme used to cross link tropocollagen? | Copper-containing lysyl oxidase |
| What is made by covalent lysine-hydroxylysine cross-linkage of many staggered tropocollagen molecules? | Collagen fibrils |
| What are the associated gene defects of Osteogenesis Imperfecta? | COLIA1 and COLIA2 |
| Osteogenesis imperfecta is seen clinically with what features? | - Multiple fractues with miniaml trauma - Blue sclerae - Tooth abnormalities (lack of dentin) - Hearing loss |
| What is the cause of hearing loss in Osteogenesis imperfecta? | Abnormal ossicles |
| Why are the teeth a target for Osteogenesis imperfecta? | Dentin is made of Collagen type I, and its deficit lead to easy wear of teeth |
| What is the treatment for OI? | Bisphosphonates to decrease risk of fracture |
| What is the MC form of inheritance seen in Osteogenesis imperfecta? | Autosomal dominant |
| What is the definition of Ehlers-Danlos syndrome? | Faulty collagen synthesis causing hyperextensible skin, hypermobile joints, and tendency to bleed |
| What are some serious complications and associations with Ehlers-Danlos syndrome? | Joint dislocation, Berry and Aortic aneurysms, and organ rupture |
| What is the MC type of Ehlers-Danlos syndrome? | Classical type (joint and skin) due to mutation in type V collagen |
| Deficiency type III procollagen. Dx? | Vascular Ehlers-Danlos syndrome |
| What is Menkes disease? | XR connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein (ATP7A) |
| What is ATP7A? | Menkes protein |
| The lack of copper leads to a decrease in function of what collagen synthesis enzyme? | Lysyl oxidase |
| What is the clinical manifestation of Menkes disease? | Brittle, "kinky" hair, growth retardation and hypotonia |
| What is elastin? | Stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava. |
| What enzyme can break Elastin? | Elastase |
| What common enzyme or protein inhibits the actions of Elastase? | alpha-1-antitrypsin (ATT) |
| What is the result of Alpha-1-antitrypsin deficiency? | Unopposed elastase activity, leading to development of COPD |
| What chromosome is affected in Marfan syndrome? | Chromosome 15 |
| AD disorder of connective tissue affecting the skeleton, heart, and eyes, with mutated FBN1 gene. Dx? | Marfan syndrome |
| What are common vascular complications of Marfan syndrome? | Cystic medial necrosis of aorta; aortic root aneurysm rupture or dissection; mitral valve prolapse |
| Description of necrosis seen in Marfan syndrome? | Cystic medial necrosis of aorta |
| How is the lens subluxation in patients with Marfan syndrome? | Upward and temporally |
| How is the lens subluxation in patients with homocystinuria? | Downwards and medially |
| What syndrome is associated with a defective fibrillin protein? | Marfan syndrome |
| What is the sheath around elastin called? | Fibrillin |
| What are the fat soluble vitamins? | A, D, E, K |
| Where are all fat soluble vitamins absorbed? | Ileum and Pancreas |
| Why are fat soluble vitamins more toxic than water soluble? | They accumulate in the fat |
| What conditions can cause Fat-soluble vitamin deficiencies? | 1. Malabsorption syndromes 2. Mineral oil intake |
| What are common examples of Malabsorption syndromes that result in Fat Soluble vitamin deficiencies? | Cystic fibrosis and Celiac disease |
| Of all the water soluble vitamins, which are the only two that get store temporarily in the body? | Cobalamin (Vit B12) in liver for 3~4 years, and Folate (Vit B9) in liver for 3~4 months |
| What are common symptoms seen in B-complex deficiencies? | Dermatitis, glossitis, and diarrhea |
| What is the common name of Vitamin B1? | Thiamine |
| What is the coenzyme associated with Thiamine? | Thiamine pyrophosphate (TPP) |
| Coenzymes associated with Vitamin B2? | FAD and FMN |
| What is another name of Vitamin B2? | Riboflavin |
| Niacin = | Vitamin B3 |
| What coenzyme is associated with Niacin? | NAD+ |
| B5: | Pantothenic acid; CoA (coenzyme) |
| What is the coenzyme of Pyridoxine? | PLP |
| Pyridoxine = | Vitamin B6 |
| What is the common name for Vitamin B7? | Biotin |
| How else is Vitamin B9 and Vitamin B12, named, respectively? | Folate and Cobalamin, respectively. |
| Functions of Vitamin A? | 1. Antioxidant 2. Constituent of visual pigments (retinal) 3. Essential for normal differentiation of epithelial cells into specialized tissue 4. Prevents squamous metaplasia |
| What type of tissue alteration or modification is prevented by Vitamin A? | Squamous metaplasia |
| What cells are greatly affected by Vitamin A aid in epithelial cell differentiation? | Pancreatic cells and Mucus-secreting cells |
| What are some old uses for Vitamin A? | 1. Measles 2. Acute Promyelocytic leukemia (APL) |
| What types of Vitamin A are often used in medicine? | Retinal, retinol, and retinoic acid |
| Which form of vitamin A is used to treat wrinkles and acne? | Topical retinol |
| In which products is vitamin A naturally found? | Liver and leafy vegetables |
| What can be used to treat severe cystic acne? | Oral isotretinoin |
| What are symptoms of Vitamin A deficiency? | 1. Night blindness 2. Dry, scaly skin (Xerosis cutis) 3. Bitot spots 4. Corneal degeneration 5. Immunosuppression |
| What is xerosis cutis? | Dry, scaly skin most likely due to Vitamin A deficiency |
| When are Bitot spots commonly seen? | Vitamin A deficiency |
| What are Bitot spots? | Keratin debris; foamy appearance on conjunctiva |
| What is Keratomalacia? | Corneal degeneration |
| What are the teratogenic effects of Vitamin A? | Cleft palate and cardiac abnormalities |
| Chronic toxicity of Vitamin A excess is clinically seen with: | Alopecia, dry skin, hepatic toxicity and enlargement, arthralgias, and idiopathic intracranial hypertension |
| Thiamine requires what cofactor? | Thiamine pyrophosphate (TPP) |
| What are the 4 enzymes that require Thiamine and TPP? | 1. Branched-chain ketoacid dehydrogenase 2. a-Ketoglutarate dehydrogenase (TCA cycle) 3. Pyruvate dehydrogenase 4. Transketolase |
| What is "linked" by Pyruvate dehydrogenase? | Glycolysis to TCA cycle |
| A deficiency in vitamin _______ will lead to a decrease action of Pyruvate dehydrogenase. | B 1 |
| Which water soluble vitamin is given first to alcoholic patients in order to prevent Wernicke encephalopathy? | Vitamin B1 |
| How is vitamin B1 diagnosis made? | Increase in RBC transketolase activity following vitamin B1 administration |
| What are some conditions seen with Vitamin B1 deficiency? | 1. Wernicke encephalopathy 2. Korsakoff syndrome 3. Wernicke-Korsakoff syndrome 4. Dry beriberi 5. Wet beriberi |
| Describe the classic triad of Wernicke encephalopathy? | Confusion, Ophthalmoplegia, and ataxia |
| Acute, life-threatening, neurologic condition due to Thiamine deficiency? | Wernicke Encephalopathy |
| Describe Korsakoff syndrome | Amnestic disorder due to chronic alcohol consumption; presents with confabulation, personality changes, and permanent memory loss. |
| How is the memory loss Korsakoff syndrome described as? | Permanent |
| What is damaged in Wernicke-Korsakoff syndrome? | Medial dorsal nucleus of thalamus, and mammillary bodies |
| What is the clinical presentation of Dry beriberi? | Polyneuropathy and symmetric muscle wasting |
| What are cardiac involvement seen in Wet beriberi? | High-output cardiac failure (dilated cardiomyopathy), edema |
| The cofactors of Vitamin B2 serve in ______________ reactions. | Redox |
| What are the associated cofactors of Riboflavin? | FAD and FMN |
| What is the most important redox reaction in which FAD and FMN are involved? | Succinate dehydrogenase reaction in the TCA cycle. |
| Riboflavin deficiency is seen with: | Cheilosis and Corneal vascularization |
| What is Cheilosis? | Inflammation of lips, scaling and fissures at the corners of the mouth |
| Vitamin B3 is derived from ________________. | Tryptophan |
| What other B-vitamins are required for the formation of Vitamin B3? | Vitamin B2 and B6 |
| What is a common condition treated with Niacin? | Dyslipidemia |
| How many ATP molecules are seen with Vitamin B3? | 3 ATP |
| What vitamin deficiency causes Pellagra? | Vitamin B3 deficiency |
| What causes of Pellagra? | 1. Severe Vitamin B3 deficiency 2. Malignant carcinoid syndrome 3. Isoniazid |
| Why does carcinoid syndrome develops Pellagra? | Increases tryptophan metabolism |
| What is Hartnup disease? | AR; deficiency of neutral amino acid (tryptophan) transporters in Proximal renal tubular cells and on enterocytes |
| What are the main symptoms of Pellagra? | Diarrhea, Dementia, and Dermatitis |
| What is the description of Dermatitis seen with Pellagra? | C3/C4 dermatome circumferential "broad collar" rash, hyperpigmentation of sun-exposed limbs |
| What are some effects of Niacin in excess? | Facial flushing by prostaglandin, hyperglycemia, and hyperuricemia |
| What is different of the Facial flushing seen with Pellagra? | It is due to prostaglandin, and not histamine |
| What can be administer to avoid Niacin-induced facial flushing? | Aspirin with Niacin |
| Podagra is often seen with excess of Vitamin ______. | B3 |
| What is an essential component of CoA? | Vitamin B5 |
| What are some important features seen with Vitamin B5 deficiency? | Dermatitis, enteritis, alopecia, and adrenal insufficiency |
| What does cofactor PLP stand for? | Pyridoxal phosphate |
| For which reactions is PLP important: | - Transamination - Decarboxylation reactions -Glycogen phosphorylase |
| What molecules, proteins and enzymes require Vit B6 for its synthesis? | Glutathione, Cystathionine, heme, niacin, histamine, and Neurotransmitters |
| Which neurotransmitters require Vit B6 for their synthesis? | Serotonin, Epinephrine, Norepinephrine, dopamine, and GABA |
| What is clinically presented in a patient with Vitamin B6 deficiency? | 1. Convulsions, hyperirritability 2. Peripheral Neuropathy 3. Sideroblastic anemia |
| What kind of anemia is seen with pyridoxine deficiency? | Sideroblastic anemia due to impaired hemoglobin synthesis and iron excess |
| What conditions predispose a patient to develop peripheral neuropathy due to Vitamin B6 deficiency? | Deficiency inducible by isoniazid and oral contraceptives |
| Biotin is a cofactor for carboxylation enzymes which add --> | 1-carbon group |
| What are 3 common enzymes that use biotin as a cofactor? | 1. Pyruvate carboxylase 2. Acetyl-CoA carboxylase 3. Propionyl-CoA carboxylase |
| What is a rare cause of biotin deficiency? | Excessive ingestion of raw egg whites |
| What is the function of of Vitamin B9? | Coenzyme for 1-carbon transfer/methylation reactions |
| Where is folate is absorbed? | Jejunum |
| What kind of anemia is seen with Folate deficiency? | Macrocytic, megaloblastic anemia |
| What drugs are associated in precipitating folate deficiency? | Phenytoin, sulfonamides, and MTX |
| What are the labs seen Macrocytic, megaloblastic anemia due to folate deficiency? | Increased homocysteine, normal methylmalonic acid levels |
| Vitamin B12 serves as a cofactor to which two main enzymes: | 1. Methionine synthase 2. Methylmalonyl-CoA mutase |
| Vitamin B12 transfers ________ groups. | CH3 |
| What is the difference anemia between Folate and Cobalamin deficiency? | Cobalamin deficiency anemia is accompanied with neurological symptoms |
| What are some causes of Cobalamin deficiency? | - Malabsorption - Lac of intrinsic factor -Absence of terminal ileum - Drugs -Insufficient intake |
| What are common malabsorption conditions that cause a deficiency in Vitamin B12? | Sprue, enteritis, Diphyllobothrium latum, achlorhydria, bacterial overgrowth, alcohol excess |
| Pernicious anemia is the MCC of: | Megaloblastic anemia due to lack of intrinsic factor |
| Which antibody is diagnostic of Pernicious anemia? | Anti-intrinsic factor antibodies |
| Vitamin C is necessary for: | - Facilitates iron absorption by reducing Fe2+ state - Hydroxylation of proline and lysine in collagen synthesis - Dopamine B-hydroxylase |
| What is the clinical characteristics of Scurvy? | Swollen gums, easy bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhage, "corkscrew" hair |
| What is the name of D3? | Cholecalciferol |
| What is the name of D2? | Ergocalciferol |
| What is the active form of Vitamin D? | 1, 25 -(OH)2 D3 (calcitriol) |
| In which organ converts Vitamin D into active form? | Kidney |
| Functions of Vitamin D: | 1. Increase intestinal absorption of Ca2+ and phosphate 2. Increase bone mineralization at low levels 3. Increase bone resorption at higher levels |
| Condition of children due to vitamin D deficiency. | Rickets |
| What is the condition of vitamin D deficiency in adults? | Osteomalacia |
| What kind of disease are seen with increased levels of Vitamin D? | Granulomatous diseases |
| What is the function of Vitamin E? | Antioxidant by protein RBCs and membranes from free radical damage |
| What are some clinical manifestations of Vitamin E deficiency? | Hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination |
| What is the risk of Vitamin E excess? | Risk of enterocolitis in infants |
| How is the difference in neurologic symptoms in Vitamin E deficiency and Cobalamin deficiency? | Vitamin E deficiency does not causes megaloblastic anemia |
| What vitamin ingestion may enhance the effects of Warfarin? | Vitamin E |
| What are some examples of Vitamin K? | Phytomenadione, phylloquinone, phytonadione, and menaquinone. |
| What is the function of of Vitamin K? | Activated by epoxide reductase to the reduced form, which is a cofactor for the gamma-carboxylation of glutamic acid residues on various proteins required for blood clotting. |
| Where is vitamin K synthesized? | Intestinal flora |
| What clotting factors require vitamin K? | II, VII, IX, X, and proteins C and S. |
| What medication inhibits the synthesis of vitamin K? | Warfarin |
| How are the changes of PT, aPTT, and BT in cases of vitamin K deficiency? | Increased PT and PTT, and a normal BT. |
| Why is a vitamin K injection given at birth? | To prevent hemorrhagic disease of the newborn |
| What are the functions or needs to Zinc? | 1. Mineral essentia. for the activity of 100+ enzymes 2. Formation of zinc fingers (transcription factor motif) |
| What are the clinical manifestations of Zinc deficiency? | Delayed wound healing, suppressed immunity, hypogonadism, decreased adult hair, dysgeusia, anosmia, acrodermatitis enteropathica |
| Dysgeusia, anosmia and cutaneous rash is presented with what kind of mineral deficiency? | Zinc |
| What are two major conditions due to a deficiency in protein-energy malnutrition? | Kwashiorkor and Marasmus |
| What are the main clinical features of Kwashiorkor? | Malnutrition, Edema, Anemia, fatty Liver, and Skin lesions (hyperkeratosis, and dyspigmentation) |
| Why is edema in Kwashiorkor? | Decrease in plasma oncotic pressure |
| Small child with swollen abdomen and skin lesions. Dx? | Kwashiorkor |
| What protein malnutrition is seen without edema? | Marasmus |
| What is the main symptoms in Marasmus? | Muscle wasting |
| What is the antidote of overdose of Methanol or Ethylene glycol? | Fomepizole |
| What enzyme is inhibited by Fomepizole? | Alcohol dehydrogenase |
| Disulfiram inhibits which enzyme? | Acetaldehyde dehydrogenase |
| What substance is accumulated that contributes to hangover symtposm? | Acetaldehyde |
| What is the limiting reagent of Ethanol metabolism? | NAD+ |
| What is the kinetics of Alcohol dehydrogenase? | Zero-order kinetics |
| What ratio is increased in Ethanol metabolism? | NADH: NAD+ |
| Which reaction of glycolysis, produces NAD+? | Pyruvate -----> Lactate |
| Which TCA cycle reaction of NADH --> NAD+? | Oxaloacetate ----> Malate |
| What are some effects of Ethanol metabolism? | 1. Pyruvate -->lactate (lactic acidosis) 2. Oxaloacetate --> malate (prevents gluconeogenesis --> fasting hypoglycemia) 3. Dihydroxyacetone phosphate --> glycerol-3-phosphate (G3P) --> hepatosteatosis |
| What cycle is disfavored by an increased NADH: NAD+? | TCA cycle |
| What metabolic processes occur exclusively in the Mitochondria? | 1. Fatty acid oxidation (B-oxidation), 2. Acetyl-CoA production 3. TCA cycle 4. Oxidative phosphorylation 5. Ketogenesis |
| What are exclusive cytoplasmic metabolic processes? | 1. Glycolysis 2. HMP shunt 3. Synthesis of steroids (SER), proteins (ribosomes, RER), fatty acids, cholesterol, and nucleotides |
| What 3 metabolic process occur in the mitochondria and the cytoplasm? | 1. Heme synthesis, 2. Urea cycle 3. Gluconeogenesis |
| What is a Kinase? | Enzyme that catalyzes the transfer of phosphate group from a high-energy molecule to a substrate |
| What is the function of a Phosphorylase? | Adds inorganic phosphate onto a substrate WITHOUT using ATP |
| What is an Phosphatase role? | Removes phosphate group from substrate |
| Catalyzes oxidation -reduction (redox) reactions? | Dehydrogenase |
| Adds hydroxyl group (-OH) onto substrate | Hydroxylase |
| What is a common example of an Hydroxylase? | Tyrosine hydroxylase |
| Pyruvate carboxylase is an _________________________. | Carboxylase |
| What is the function of a Carboxylase? | Transfers CO2 groups with the help of biotin |
| What is needed in order to work any carboxylase? | Biotin |
| What is the main action of an mutase? | Relocates a functional group within a molecule |
| Joins to molecules together using a source of energy? | Synthase/synthetase |
| What is the MC high-energy molecule used by a kinase? | ATP |
| Fructose-1, 6-bisphosphatase is an example of ________________. | Phosphatase |
| What is the Rate limiting enzyme of Glycolysis? | Phosphofructokinase-1 (PFK-1) |
| What are stimulators (positive regulators) of Glycolysis? | AMP, and fructose-2, 6-bisphosphate |
| ATP and citrate are: | Inhibitors of Glycolysis |
| What is the rate limiting step of Gluconeogenesis? | Fructose-1, 6- bisphosphatase |
| What is a common negative regulator of Gluconeogenesis? | Fructose-2, 6-bisphosphate |
| What is the rate limiting enzyme of TCA cycle? | Isocitrate dehydrogenase |
| The enzyme is an Glycogen synthase is the rate limiting enzyme of ___________________. | Glycogenesis |
| What is the rate-limiting enzyme of glycogenolysis? | Glycogen phosphorylase |
| G6PD is the rate limiting enzyme is of __________________. | HMP shunt |
| What enzyme is rate limiting of De novo pyrimidine synthesis? | Carbamoyl phosphate synthetase II |
| PRPP is the rate limiting enzyme of ______________________. | De novo purine synthesis |
| What is a positive regulator of Urea cycle? | N-acetylglutamate |
| What is the rate limiting enzyme of Urea cycle? | Carbamoyl phosphate synthetase |
| What is the rate limiting enzyme of Fatty acid synthesis? | Acetyl-CoA carboxylase |
| Fatty acid oxidation uses ________________________ as its rate limiting enzyme. | Carnitine acyltransferase I |
| Cholesterol synthesis rate limiting enzyme is? | HMG-CoA reductase |
| HMG-synthase is the rate limiting enzyme of which metabolic process? | Ketogenesis |
| Enzyme deficiency of mild Galactosemia? | Galactokinase |
| What enzyme is deficient in Severe Galactosemia? | Galactose-1-phosphate uridyltransferase |
| What is the defective enzyme in von Gierke disease? | Glucose-6-phosphatase |
| Deficient Fructokinase. Dx? | Essential fructosuria |
| What condition is due to Aldolase B deficiency? | Fructose intolerance |
| What aerobic shuttle is used by the heart and liver in ATP production? | Malate-Aspartate shuttle |
| How many ATP molecules are produced by each glucose molecule via the Malate-aspartate shuttle? | 32 |
| What "shuttle" is used in muscle in glycolysis in production of ATP? | Glycerol-3-phosphate shuttle |
| What is the net ATP production by aerobic glycolysis via the Glycerol-3-phosphate shuttle? | 30 |
| How many ATP molecules / glucose molecule via the anaerobic glycolysis? | 2 net ATP |
| What metal (poison) causes glycolysis to produce zero net ATP? | Arsenic |
| What are the most common Universal electron acceptors? | 1. Nicotinamides (NAD+, NADP+) 2. Flavin nucleotides (FAD+) |
| FAD+ comes from vitamin ________. | B2 |
| NAD+ and NADP+ comes from vitamin _____. | B3 |
| What processes or enzymes use NADPH? | 1. Anabolic processes 2. Respiratory burst 3. Cytochrome P-450 system 4. Glutathione reductase |
| NAD+ is generally used in ____________ processes to carry reducing equivalents away as NADH. | Catabolic |
| NADPH is a product of ______________________. | HMP shunt |
| What kinases are used to phosphorylation of glucose to yield Glucose-6-phosphate? | Hexokinase and Glucokinase |
| Hexokinase is used in most tissues except for: | Liver and Pancreatic B-cells |
| Which cells use Glucokinase? | Liver, B-cells of pancreas |
| What is the role or function of Glucokinase at high glucose concentration? | Helps to store glucose in liver |
| Which has higher affinity, Hexokinase or Glucokinase? | Hexokinase |
| While Hexokinase has a higher affinity, it also has a ________ capacity. | Lower |
| What protein reverses the actions of FBPase-2 and PFK-2? | Protein kinase A |
| In the regulation of Fructose-2, 6-bisphosphate, which bifunctional enzyme is active in fasting state? | FBPase-2 |
| PFK-2 enzyme is active in which state? | Fed state |
| Increased activity of FBPase-2 leads to overall increase of __________________________. | Gluconeogenesis |
| Upregulation or activity of PFK-2 followed by PFK-1, causes a preference to __________________, metabolic process activity. | Glycolysis |
| What enzyme is used to convert Fructose-1, 6-BP into Fructose-6-phosphate? | FBPase-1 |
| Increased glucagon is seen in _______________ state. | Fasting |
| Increased levels of insulin are seenin __________________ state. | Fed |
| More glycolysis and less gluconeogenesis is seen in _______ state. | Fed |
| Induced less glycolysis and more gluconeogenesis is seen in ________ state. | Fasting |
| What complex links glycolysis and TCA cycle? | Pyruvate dehydrogenase complex |
| Which state, fed or fasting, activates the Pyruvate dehydrogenase complex? | Fed state |
| Which enzyme has a similar role to Pyruvate dehydrogenase complex? | a-ketoglutarate dehydrogenase |
| What are the 5 cofactors required by Pyruvate dehydrogenase? | 1. Thiamine pyrophosphate (B1) 2. Lipoic acid 3. CoA 4. FAD 5. NAD+ |
| What 3 conditions activate the Pyruvate Dehydrogenase complex ? | INCREASED: - NAD+/NADH ratio - ADP - Ca2+ |
| What is the classical description of Arsenic poisoning breath? | Garlic |
| Arsenic inhibits with Pyruvate dehydrogenase complex cofactor? | Lipoic acid |
| What is the mode of inheritance of Pyruvate dehydrogenase deficiency? | X-linked |
| What is caused by Pyruvate dehydrogenase complex deficiency? | Buildup of pyruvate that gets shunted to 1) lactate via LDH, and 2) alanine via ALT |
| What serum abnormality is seen since infancy in Pyruvate dehydrogenase complex deficiency? | Increased serum alanine |
| What is the treatment of Pyruvate dehydrogenase complex deficiency? | Increase intake of ketogenic nutrients (lysine and leucine rich products) |
| Neurologic defects + lactic acidosis + increased serum alanine in a 2 year old patient. Dx? | Pyruvate dehydrogenase complex deficiency |
| What are the four destinations of Pyruvate metabolism? | Alanine, Oxaloacetate, Acetyl-CoA, and Lactate |
| Which are the two fates of Pyruvate that occur in the cytosol? | Alanine (Cahill cycle) and Lactae (Cori cycle) |
| Which ar the two mitochondrial fates of Pyruvate? | Oxaloacetate and Acetyl -CoA |
| What are uses or purposes of Oxaloacetate? | 1. Replenish TCA cycle 2. Used in Gluconeogenesis |
| What enzyme is used for the transition of Glycolysis to the TCA cycle? | Pyruvate dehydrogenase |
| The production of Lactate, signals the: | End of anaerobic glycolysis |
| Lactate production is the major pathway of ATP production in which tissues? | RBCs, WBCs, kidney medulla, lens, testes, and cornea |
| What cofactor is used by Lactic acid dehydrogenase? | B3 |
| What enzyme is required to by Pyruvate in order to concert into Acetyl-CoA? | Pyruvate dehydrogenase (PDH) |
| Which enzyme is PC, and is used for? | Pyruvate carboxylase; used to convert Pyruvate into Oxaloacetate |
| How many carbon dioxide molecules are produced by the TCA cycle? | 2 |
| What is another name for the TCA cycle? | Krebs cycle |
| Which TCA cycle enzyme shares the same cofactors as Pyruvate dehydrogenase complex? | alpha-Ketoglutarate dehydrogenase complex |
| What are the 3 irreversible TCA cycle enzymes? | Citrate synthase, Isocitrate dehydrogenase, and a-KG dehydrogenase |
| Enzyme used in Complex II of the ETC? | Succinate dehydrogenase |
| Common inhibitors of ETC Complex IV? | Cyanide, CO, and Azide |
| Cyanide poisoning causes a decrease in aerobic ATP production due to: | Inhibition of Complex IV in the ETC |
| Which drug inhibits Complex I? | Rotenone |
| Complex III in the ETC is inhibited by ______________________. | Antimycin A |
| Oligomycin inhibits or halts ATP production by : | Inhibition of Complex V in the ETC |
| Which type of Oxidative phosphorylation agents cause a decrease in proton gradient in the ETC? | Electron transport inhibitors and Uncoupling agents |
| What are common Electron transport inhibitors? | Rotenone, Antimycin A, Cyanide, carbon monoxide, and azide |
| 2,4-Dinitrophenol is an __________________, used illicity to loss weight. | Uncoupling agent |
| Aspirin and Thermogenin are both ________________ agents. | Uncoupling |
| What is the most common ATP synthase inhibitor? | Oligomycin |
| What is the primary function of Gluconeogenesis? | Maintain euglycemia during fasting states |
| What is caused by a deficiency in key gluconeogenic enzymes? | Hypoglycemia |
| Why do even-chain fatty acids cannot produce new glucose? | They yield only one acetyl-CoA equivalent |
| Why do only odd-chain fatty acids undergo gluconeogenesis, and serve as glucose source? | These yield 1 propionyl-CoA |
| Another name for the HMP shunt? | Pentose Phosphate Pathway |
| Which product is primarily provided by the HMP shunt? | NADPH |
| How much ATP is used or produced by the HMP shunt? | None |
| What are the two main products of the HMP shunt? | 1. NADPH 2. Ribose for nucleotide synthesis |
| Which sites have high HMP shunt activity? | Lactating mammary glands, liver, adrenal cortex, and RBCs |
| What are the two divisions of the HMP shunt? | Oxidative (irreversible) and Nonoxidative (reversible) |
| Which is the main enzyme involved in the Oxidative reaction of the HMP shunt? | Glucose-6-P dehydrogenase |
| What are the two enzymes involved in non-oxidative part of the HMP shunt? | Phosphopentose isomerase, and Transketolase |
| What vitamin is required, as cofactor, in the nonoxidative reaction of the HMP shunt? | Vitamin B1 |
| Which part or reaction produces Ribose-5-P of the HMP shunt? | Nonoxidative |
| Carbon dioxide, 2 NADPH, and Ribulose-5-P are products of: | Oxidative reaction of the HMP shunt |
| What enzyme is needed to keep glutathione reduced? | NADPH |
| The reduced form of glutathione functions by: | Detoxification of free radicals and peroxides |
| What enzyme deficiency can, most commonly, cause a deficiency in NADPH? | G6PD |
| What is the most common human enzyme deficeincy? | G6PD deficiency |
| G6PD deficiency is an _________________ disorder. | X-linked recessive |
| Which population is at higher risk of developing G6PD deficiency? | African Americans |
| What is a inadvertent benefit of G6PD deficiency? | Increase malarial resistance |
| What kind of anemia is produced in G6PD deficiency? | Hemolytic anemia due to poor RBC defense against oxidizing agents |
| What are some oxidizing agents that precipitate G6PD deficiency? | Fava beans, sulfonamides, nitrofurantoin, primaquine/chloroquine, antituberculosis drugs |
| Which condition is seen with Heinz bodies and Bite cells? | G6PD deficiency |
| What are Heinz bodies? | Denatured globin chains precipitate within RBCs due to oxidative stress |
| What are Bite cells? | Result form the phagocytic removal of Heinz bodies by splenic macrophages |
| In a patient with Essential Fructosuria, which becomes the primary pathways for converting fructose into fructose-6-phosphate? | Hexokinase |
| What are the symptoms of essential Fructosuria? | Fructose in blood and urine |
| Which fructose metabolism is most severe? | Hereditary fructose intolerance due to Aldolase B deficiency |
| Both fructose metabolism disorders are of ______________________ inheritance. | Autosomal recessive |
| What metabolic processes are inhibited in Fructose intolerance? | Glycogenolysis and Gluconeogenesis |
| Which is a common vignette scenario of a person with Fructose intolerance? | Acute development of hypoglycemia following consumption of fruit, juice, or honey. |
| What is the result of a urine dipstick test in Fructose intolerance? | Negative |
| Which is the defective or absent enzyme of Fructose intolerance? | Aldolase B |
| What are the clinical manifestations of Aldolase B deficiency? | Hypoglycemia, jaundice, cirrhosis, and vomiting. |
| Which Galactose metabolism disorder is most severe? | Classic Galactosemia |
| Hereditary deficiency of Galactokinase. Dx? | Galactokinase deficiency |
| What are the most common clinical symptoms of Galactokinase deficiency? | Galactose in blood and urine, infantile cataracts, and possible failure to track objects or develop social smile. |
| Classical Galactosemia is due to: | Absence of galactose-1-phosphate uridyltransferase |
| What is accumulated in the lens of the eye in a patient with Classic Galactosemia? | Galactitol |
| What are the classical symptoms and presentation of a infant with Classic Galactosemia? | Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, and predisposition to E. coli sepsis in neonates. |
| What kind of sepsis is possibly seen in a neonate with Classic Galactosemia? | E. coli |
| Which advance condition may lead to phosphate depletion? | Classic Galactosemia |
| What is an alternate form of trapping glucose in the cell? | Sorbitol |
| What enzyme is used to convert glucose into sorbitol? | Aldose reductase |
| What is the alcohol counterpart of glucose? | Sorbitol |
| What are some manifestations of osmotic damage due to sorbitol accumulation? | Cataracts, retinopathy, and peripheral neuropathy |
| Enzyme that converts Sorbitol into Fructose? | Sorbitol dehydrogenase |
| Which enzyme converts Glucose ----> Sorbitol? | Aldose reductase |
| Where does Lactase work? | Intestinal brush border to digest lactose |
| Lactose breaks down lactose into ______ and ___________. | Glucose and Galactose |
| What is the primary reason of Lactase deficiency? | Absence of lactase-persistence allele |
| Loss of intestinal brush border due to GI infection, is the secondary cause of _____________________ deficiency. | Lactase |
| What are the corresponding labs of stool and breath analysis of a patient with Lactose intolerance? | Decreased pH and breath shows hydrogen content with lactose hydrogen breath test |
| Patient with bloating, caprms, flatulence, and osmotic diarrhea after eating ice cream. Dx? | Lactase deficiency |
| Which isoform of amino acids is found in proteins? | L-amino acids |
| Mnemonic for Essential amino acids | PVT TIM HaLL |
| Which are all the essential amino acids? | Phenylalanine, Valine, Tyrosine, Threonine, Isoleucine, Mthione, Histidine, Leucine, and Lysine |
| Which are the the Essential purely Glucogenic amino acids? | Methionine, Histidine, and valine |
| Purely Ketogenic amino acids? | Leucine and Lysine |
| Isoleucine, Phenylalanine, Threonine, and Tyrosine are: | Both, Glucogenic and Ketogenic amino acids |
| Which are the 2 acidic amino acids? | Aspartic acid and Glutamic acid |
| Which are the 3 basic amino acids? | Arginine, histidine, and lysine |
| Essential amino acids are categorized into which categories? | Glucogenic, Ketogenic , and Mixed (ketogenic/glucogenic) |
| Which is the most basic amino acid? | Arginine |
| Which two basic amino acids are required in periods of growth? | Arginine and histidine |
| What is the charge of acidic amino acids at body pH? | Negative |
| What cycle produces common metabolites of amino acids such as Pyruvate and Acetyl-CoA, which serve as metabolic fuels? | Urea cycle |
| Excess urea produced in Urea cycle is excreted via the _____. | Kidneys |
| The Cahill cycle connects the _____ with the _______, in order to secrete urea (NH3). | Muscle to the liver |
| What is a common hereditary form of Hyperammonemia? | Urea cycle enzyme deficiencies |
| What happens in the CNS in cases of excess NH3? | NH3 deprest glutamate (GABA) in CNS and a-Ketoglutarate leading to inhibition of TCA cycle. |
| What are clinical manifestation of Ammonia accumulation? | Flapping tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision |
| What medication may be given to reduced amononal levels? | 1. Lactulose 2. Rifaximin and Neomycin 3. Benzoate, phenylacetate |
| What is the MOA of Lactulose? | Acidify the GI tract and trap NH4+ for excretion |
| What is the reason of RIfaximin or Neomycin use to reduce ammonia levels? | Decrease colonic ammoniagenic bacteria |
| What is the most common urea cycle disorder? | Ornithine transcarbamylase deficiency |
| Which condition is due to the body's inability to eliminate ammonia? | Ornithine transcarbamylase deficiency |
| What are the common findings of Ornithine transcarbamylase deficiency? | - Increased orotic acid in blood and urine - Decreased BUN - Symptoms of Hyperammonemia |
| What is a key clinical finding that differentiates Orotic aciduria from Ornithine Transcarbamylase deficiency? | Ornithine transcarbamylase deficiency does NOT present with megaloblastic anemia |
| What is the inheritance mode of Ornithine transcarbamylase deficiency? | X-linked recessive |
| What are the derivatives of Tryptophan? | NIacin, Serotonin, and Melatonin |
| What are the derivatives of Glycine? | Porphyrin --> Heme |
| GABA is made from which amino acid? | Glutamate |
| What are the 3 main derivatives of Arginine? | Creatine, Urea, and Nitric Oxide |
| Phenylalanine + Tetrahydrobiopterin (BH4) = | Tyrosine |
| Dopamine needs what vitamin in order to produce or convert into Norepinephrine? | Vitamin C |
| NE + SAM ---------> | Epinephrine |
| Phenylalanine hydroxylase deficiency. Dx? | PKU |
| What enzyme is deficient in PKU? | Phenylalanine hydroxylase |
| PKU may be due to deficiency in which enzyme and cofactor? | 1. Phenylalanine hydroxylase 2. BH4 |
| What enzyme deficiency leads to Alkaptonuria? | Homogentisate oxidase |
| Decreased levels of Maleyl Acetoacetic acid most likely is due to ____________________, which has a deficiency in _________________. | Alkaptonuria; Homogentisate oxidase |
| Albinism is due to deficiency in which enzyme? | Tyrosinase |
| PKU is seen with elevated levels of _________________. | Phenylalanine |
| Malignant PKU is due to deficiency in _________________. | BH4 |
| How soon is can PKU be diagnosed? | 2-3 days after birth |
| How are increased levels of Phenylalanine represented in urine? | Excess phenyl ketones |
| What are clinical findings of Phenylketonuria (PKU)? | Intellectual disability, growth retardation, seizures, fair complexion, eczema, and musty body odor |
| Musty body odor. Dx? | PKU |
| What is increased in the diet of a PKU patient? | Increased consumption or tyrosine |
| What food product do PKU patients must avoid at all costs from ingestion? | Artificial sweetener aspartame, since it contains phenylalanine |
| What is the MCC of Maternal PKU? | Lack of proper dietary therapy during pregnancy |
| What the MCC of Maple Syrup urine disease? | Blocked degradation of branched amino acids due to decreased branched-chain a-ketoacid dehydrogenase (B1) |
| What are the branched amino acids affected in Maple Syrup urine disease? | Isoleucine, Leucine, and Valine |
| What is the characteristic smell or odor of urine a patient with maple syrup urine disease? | Maple syrup/ or burnt sugar |
| What is the most elevated a-ketoacid in MSUD? | Leucine |
| What is the mode of inheritance of MSUD? | Autosomal recessive |
| What are the findings seen with Alkaptonuria? | Bluish-black connective tissue, ear cartilage, and sclerae |
| Urine turns black after prolonged exposure to air. Dx? | Alkaptonuria |
| Why is Alkaptonuria presented with debilitating arthralgias? | Homogentisic acid toxic to cartilage |
| What is the mode of inheritance of all types of Homocystinuria? | Autosomal recessive |
| What are the 3 types/ causes of Homocystinuria? | 1. Cystathionine synthase deficiency 2. Decreased affinity of cystathionine synthase for pyridoxal phosphate 3. Methionine synthase deficiency |
| What are the clinical manifestations of Homocystinuria? | - Severely elevated levels of Homocysteine in urine - Osteoporosis - Marfanoid habitus - Lens subluxation (down and in) - CV effects (stroke and MI) - Kyphosis - Intellectual disability |
| What are the Cardiovascular effects seen in Homocystinuria? | Thrombosis and atherosclerosis ---> Stroke and MI |
| What vitamin is required for Methionine synthase to produce Methionine? | Vitamin B12 |
| Homocysteine + Serine require Vitamin ______ and _________________ to produce cystathionine and later Cysteine. | Vitamin B6; Cystathionine synthase |
| Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cysteine, Ornithine, Lysine, and Arginine. Dx? | Cystinuria |
| What test is diagnostic for Cystinuria? | Urinary cyanide-nitroprusside test |
| What amino acids are not reabsorbed n Cystinuria patients? | Cysteine, Ornithine, Lysine, and Arginine |
| Hexagonal cystine stones. Dx? | Cystinuria |
| How is Cystine formed? | 2 Cysteines connected by a disulfide bond |
| What diuretics can be used to alkalinize urine in Cystinuria patients? | Potassium citrate, acetazolamide |
| What stain is useful to identify glycogen storage diseases? | Periodic acid-Schiff stain |
| What is the name of the Type I glycogen storage disease? | Von Gierke disease |
| Name of type II glycogen storage disease? | Pompe disease |
| Cori disease if type ______ (glycogen storage disease). | III |
| What is the name of Type V Glycogen Storage disease? | McArdle disease |
| Deficient in Glucose-6-Phosphatase. Dx? | Von Gierke disease |
| What metabolic processes are inhibited in Von Gierke disease? | Gluconeogenesis and Glycogenolysis |
| What the characteristics findings of von Gierke disease? | - Severe fasting hypoglycemia, - Greatly Glycogen in liver and kidneys - Blood lactate - Gout due to increased uric acid - Hepatomegaly and renomegaly |
| Clinical findings of Pompe disease: | Cardiomegaly, HCM, hypotonia, exercise intolerance and early death. |
| What enzyme is deficient in Pompe disease? | Lysosomal acid a-1,4-glucosidase |
| What is a milder form of von Gierke disease? | Cori disease |
| Deficient enzyme of Cori disease? | Debranching enzyme (a-1,6-glucosidase) |
| Deficient skeletal muscle glycogen phosphorylase. Dx? | McArdle disease |
| What is another name of Skeletal muscle glycogen phosphorylase? | Myophosphorylase |
| What is a Hallmark feature of McArdle disease? | Flat venous lactate curve with normal rise in ammonia levels during exercise |
| How is blood serum affected in Type V Glycogen storage disease? | Unaffected |
| What causes the muscle pain in McArdle disease? | Increased glycogen in muscle, but the muscle cannot break it down --> painful Muscle cramps, Myoglobinuria (red urine), with strenuous exercise, and arrhythmia form electrolyte abnormalities. |
| What is Glycogen? | Stored form of glucose in the liver |
| What is Glucagon? | Secreted from alpha cells of the pancreas |
| Glucagon breaks into ___________ and ____________ in the liver. | Glucose and Glycogen |
| What are the main two divisions of Lysosomal Storage diseases? | Sphingolipidoses and Mucopolysaccharidoses |
| What are the two Mucopolysaccharidoses? | Hurler syndrome and Hunter syndrome |
| What are the clinical findings of Hurler syndrome? | Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly. |
| Deficiency of alpha-L-iduronidase. Dx? | Hurler syndrome |
| What is accumulated in Hurler syndrome and Hunter syndrome? | Heparan sulfate, dermatan sulfate |
| What is the mode of inheritance of Hunter syndrome? | X-linked recessive |
| Mild Hurler + aggressive behavior, no corneal clouding. Dx? | Hunter syndrome |
| Which enzyme is deficient in Hunter syndrome? | Iduronate-2-sulfatase |
| What are classical findings of Tay-Sachs disease? | Progressive neurodegeneration, developmental delay, "cherry-red" spot on macula, lysosomes with onion skin, no hepatomegaly. |
| Progressive neurodegeneration + "cherry-red" spot on macula + Lysosomes with onion skin. Dx? | Tay-Sachs disease |
| Deficiency in Hexosaminidase A. Dx? | Tay-Sachs disease |
| Accumulation of GM2 ganglioside. Dx? | Tay-Sachs disease |
| What substrate is accumulated in Tay-Sachs disease? | GM2 ganglioside |
| Which lysosomal storage disease is seen with Hepatosplenomegaly, Tay-Sachs or Niemann-Pick disease? | Niemann-Pick disease |
| Which are the two Sphingolipidoses seen with "cherry-red" spot on macula? | Tay-Sachs disease and Niemann-Pick disease |
| Which is the only Sphingolipidoses with XR inheritance? | Fabry disease |
| Histology of Tay-Sachs disease? | Lysosomes with onion skin |
| What is the early triad of Fabry disease? | 1. Episodic peripheral neuropathy 2. Angiokeratomas 3. Hypohidrosis |
| What are the late manifestations of Fabry disease? | Progressive renal failure and Cardiovascular disease |
| What enzyme is deficient in Fabry disease? | a-galactosidase A |
| What substrate is accumulated in Fabry disease? | Ceramide trihexoside |
| Increased levels of Ceramide trihexoside. Dx? | Fabry disease |
| Central and peripheral demyelination with ataxia, dementia, are clinical findings of _______________________. | Metachromatic leukodystrophy |
| Arylsulfatase A deficiency leads to development of __________________________. | Metachromatic leukodystrophy |
| Which substrate is accumulated in Metachromatic leukodystrophy? | Cerebroside sulfate |
| Which myelinating cells are destroyed in Krabbe disease? | Oligodendrocytes |
| Enzyme deficient in Krabbe disease | Galactocerebrosidase |
| Which lysosomal storage condition presents with globoid cells? | Krabbe disease |
| Elevated Galactocerebroside and psychosine are seen in: | Krabbe disease |
| What are key findings of Krabbe disease? | Peripheral neuropathy, obstruction of oligodendrocytes, developmental delay, optic atrophy, and globoid cells |
| What is the most common Lysosomal storage disease? | Gaucher disease |
| What enzyme is missing or deficient in Gaucher disease? | Glucocerebrosidase |
| What are Gaucher cells? | Lipid-laden macrophages resembling crumpled tissue paper |
| Which Lysosomal storage diseases associated with Pancytopenia? | Gaucher disease |
| Another way to refer to Glucocerebrosidase? | B-glucosidase |
| What are key bone features of Gaucher disease? | Osteoporosis, avascular necrosis of femur, and bone crisis |
| Enlarged liver and spleen, and constant bone fractures + tender femur. Dx? | Gaucher disease |
| What enzyme is deficient in Niemann-Pick disease? | Sphingomyelinase |
| The absence of Sphingomyelinase in _________________ disease, leads to accumulation of ___________________. | Niemann-Pick disease; Sphingomyelin |
| (+) Foam cells + Increased levels of Sphingomyelin. Dx? | Niemann-Pick disease |
| What condition of lysosomal storage is seen with Foam cells? | Niemann-Pick disease |
| What are the classic findings of Niemann-Pick disease? | Progressive neurodegeneration, hepatosplenomegaly, foam cells, and "cherry-red" spot on macula |
| What are foam cells? | Lipid-laden macrophages, seen in Niemann-Pick disease |
| What race is in increased risk of developing Tay-Sachs, Niemann-Pick, and Gaucher disease? | Ashkenazi Jews |
| In fatty acid synthesis what needs to be transported from the Mitochondria to the Cytosol? | Citrate |
| What tissues have the highest levels of fatty acid synthesis? | Liver, lactating mammary glands, and adipose tissue |
| Fatty acid degradation goes from the ______________ to the ____________. | Cytoplasm ---> ---> Mitochondria |
| What is the required transport in Long-chain fatty acid degradation? | Carnitine-dependent transport |
| What is the main defect in Systemic Primary (1) carnitine deficiency? | Inherited defect in transport of LCFAs ito mitochondria --> toxic accumulation |
| Hypoketotic Hypoglycemia is seen with: | Primary carnitine deficiency and Medium-chain acyl-CoA dehydrogenase deficiency |
| What is the pathogenesis of Medium-chain acyl-CoA dehydrogenase deficiency? | Decreased ability to break down fatty acids into acetyl-CoA leading to accumulation of fatty acyl carnitines in the blood with hypoketotic hypoglycemia |
| What is probable cause of death in an infant in a prolonged fasting state? | Medium-chain acyl-CoA dehydrogenase deficiency |
| Associated conditions that increase the production of Ketone bodies: | Prolonged starvation, Diabetic Ketoacidosis, and alcoholism |
| Which TCA product is either depleted or stimulated into malate, that causes an increase in Ketone production? | Oxaloacetate |
| Two commonly ketone bodies used in the muscle and brain? | Acetoacetate and B-hydroxybutyrate |
| Ketone bodies give what kind of breath smell? | Fruity odor |
| A patient with a fruity breath smell is suspected of elevated ________________. | Ketone bodies |
| Which cells cannot utilize ketones? | RBCs |
| What enzyme is used in ketone production? | HMG-CoA lyase |
| How many calories are per gram of carbohydrate and protein? | 4 calories |
| 1 gram of alcohol has how many calories? | 7 calories |
| 1 gram of fatty acid is equal to _____________ kcal. | 9 |
| What is the major source of glucose in a fasting state? | Hepatic glycogenolysis |
| What is the source of glucose in a fed state? | Glycolysis and aerobic respiration |
| In a fasting state, what stimulates the use of fuel reserves? | Glucagon and epinephrine |
| In starvation, glycogen is depleted after how many days? | 1 day |
| Why can't RBCs use ketones for energy? | Lack mitochondria |
| What are some ways blood glucose is maintained in a person in starvation for 1-3 days? | 1. Hepatic glycogenolysis 2. Adipose release of FFA 3. Muscle and liver, which shift fuel use form glucose to FFA 4. Hepatic gluconeogenesis |
| What is the main source of energy in a starvation state greater than 3 days? | Ketone bodies |
| What occurs once all adipose stores, that produce ketone bodies, are depleted? | Vital protein degradation accelerates, leading to organ failure and death |
| What is the function of Hepatic Lipase? | Degrades Triglycerides remaining in IDL |
| Degrades TGs stored in adipocytes | Hormone-sensitive lipase |
| What is the role or function of Lecithin-cholesterol acyltransferase? | Catalyzes esterification of 2/3 of plasma cholesterol |
| What is the role of Lipoprotein lipase? | Degreades TGs circulating chylomicrons and VLDLs |
| Where is Lipoprotein lipase (enzyme) found? | Vascular endothelial surface |
| What enzyme degrades dietary TGs in the small intestine? | Pancreatic lipase |
| What enzyme helps the conversion of Nascent (immature) HDL into mature HDL? | LCAT |
| What is the function of Apolipoprotein E? | Mediates remnant uptake |
| Apo E is seen in which types of cholesterol? | All |
| What form of cholesterol has Apo A-I? | HDL |
| What is the role of Apo-A-1? | Activates LCAT |
| The lack of Apo AI leads to ----> | No mature HDL |
| Lipoprotein lipase Cofactor that Catalyzes Cleavage. | Apo C-II |
| Which cholesterol presentations have Apo C-II? | Chylomicron, VLDL, adn HDL |
| What is the function of Apo B-48? | Mediates chylomicron secretion into lymphatics |
| Apo B-48 is positive for: | Chylomicrons and Chylomicron remnant |
| Function of Apo B-100? | Binds LDL receptor |
| Only particles form the ______________ have Apo B-100 activity. | Liver |
| What are lipoproteins made of? | Cholesterol, TGs, and phospholipids |
| Which type of Lipoproteins carry the highest amount of cholesterol? | LDL and HDL |
| LDL transports cholesterol from: | Liver to tissues |
| HDL transports cholesterol from: | Periphery to Liver |
| Which is the "healthy" cholesterol? | HDL |
| Why is HDL "healthy" cholesterol? | Brings peripheral cholesterol to the liver to be metabolised and excreted. |
| What is the function and role of cholesterol? | Needed to maintain cell membrane integrity and synthesize bile acid, steroids, and vitamin D |
| Which cells secrete chylomicrons? | Intestinal epithelial cells |
| What are the delivery paths of Chylomicrons? | 1. Delivery TGs to peripheral tissues 2. Delivers cholesterol to liver in the form of chylomicron remnants |
| Delivers hepatic TGs to peripheral tissue. | VLDL |
| What is the delivery done by LDL? | Hepatic cholesterol to peripheral tissues |
| How is LDL formed? | By hepatic lipase modification of IDL in the liver and peripheral tissue |
| How is LDL taken up by target cells? | Via receptor -mediated endocytosis |
| What is the main function of HDL? | Mediates reverse cholesterol transport from periphery to liver |
| Repository for apolipoproteins C and E? | HDL |
| Alcohol increases the synthesis of which lipoprotein? | HDL |
| What organs usually secrete HDL? | Liver and intestine |
| Which lipoproteins are absent in Abetalipoproteinemia? | Chylomicrons, VLDL, and LDL |
| Which Apolipoproteins are absent in Abetalipoproteinemia? | ApoB-48 and ApoB-100 |
| What are the late manifestations of Abetalipoproteinemia? | Retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, acanthosis |
| What is the treatment for Abetalipoproteinemia? | Restriction of Long-Chain fatty acids and large doses of Vitamin E |
| Reason for spinocerebellar degeneration in Abetalipoproteinemia? | Vitamin E deficiency |
| Type I dyslipidemia is known as: | Hyperchylomicronemia |
| What are the clinical manifestations of Hyperchylomicronemia? | Pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas; Creamy layer in supernatant |
| What is the pathogenesis of Hyperchylomicronemia? | Lipoprotein lipase or apolipoprotein C-II deficiency |
| What is lipids are elevated in Type I familial dyslipidemia? | Chylomicrons, TG, and cholesterol |
| Another name for Type II Familial Dyslipidemia? | Familial hypercholesterolemia |
| What is the pathogenesis of Familial hypercholesterolemia? | Abscent of defective LDL receptors, or defective ApoB-100 |
| What are the clinical manifestations of Familial hypercholesterolemia? | Accelerated atherosclerosis, tendon xanthomas, and corneal arcus |
| What is the most commonly affected tendon by a xanthoma in Familial hypercholesterolemia? | Achilles |
| Defective LDL receptor. Dx? | Familial hypercholesterolemia |
| Defective ApoB-100. Dx? | Familial hypercholesterolemia |
| Defective ApoE. Dx? | Dysbetalipoproteinemia |
| In type IIa Familial hypercholesterolaemia, what are the main blood lipids elevations? | LDL and cholesterol |
| Besides LDL and cholesterol, what other lipid is increased in blood in Type IIb Familial hypercholesterolemia? | VLDL |
| What are the clinical manifestations of Dysbetalipoproteinemia? | Premature atherosclerosis, tuberoeruptive xanthomas, palmar xanthomas |
| Hepatic overproduction of VLDL, describes the pathogenesis of which familiar dyslipidemia? | Hypertriglyceridemia |
| What is the common name of Type IV familial dyslipidemia? | Hypertriglyceridemia |
| What another name for Type III familial dyslipidemia? | Dysbetalipoproteinemia |
| Which are the Autosomal recessive Familial dyslipidemias? | Type I and Type III |
| Type II and Type IV familiar dyslipidemias are of __________ __________ inheritance. | Autosomal Dominant |
| Which lab procedure is used to amplify a desired fragment of DNA? | PCR |
| What are some examples of diseases in which PCR is a good diagnostic tool? | Neonatal HIV, herpes encephalitis |
| What are the three steps of PCR mode of action? | 1. Denaturation 2. Annealing 3. Elongation |
| Describe the Denaturation process in PCR. | DNA is heated to ~95 C to separate the strands |
| Annealing in PCR refers to: | Denatured sample to cool off to ~55 C |
| What is added to the DNA sample in the Annealing process of PCR? | DNA dimers, a heat-stable DNA polymerase (Taq), and deoxynucleotide triphosphates (dNTPs) |
| What is the Elongation step of PCR? | Temperature is increased to ~72 C. DNA pol attaches dNTPs to the strand to replicate the sequence after each primer |
| The phrase "heating and cooling cycles until the DNA sample size is sufficient" can be a reference to which lab technique? | PCR |
| What is CRISPR/Cas9? | A genome editing tool, derived form bacteria. Composed of an endonuclease and a guide RNA sequence that binds to a complementary target DNA sequence. |
| What is the endonuclease in CRISPR/Cas9? | Cas9, which cleaves dsDNA |
| Southern Blot identifies _____________. | DNA |
| Northern Blot identifies _____________. | RNA |
| Western blot identifies ______________. | Protein |
| What is used prior to Southern blot plotting, to separate DNA small pieces? | Gel electrophoresis |
| What is the filter used in Southern blotting? | Radiolabeled DNA probe that recognizes and anneals to its complementary strand |
| Cleaved DNA --> Gel electrophoresis --> Filter placement --> visualized DNA on film. Describes which lab technique? | Southern blotting |
| What is the main procedural difference between Northern and Southern blotting? | RNA sample in Northern blotting is ELECTROPHORESED. |
| Northern blotting is useful when studying ______ levels, which are reflective of ____________________. | mRNA levels ===== Gene expression |
| Labeled antibody used | Western blot |
| Once protein is separated by electrophoresis, it is transferred to a ________________, in western blotting? | Membrane |
| Which blotting technique identifies DNA-binding proteins? | Southwestern blot |
| Which are them most common DNA-binding proteins identified by SW blot? | Transcription factors |
| What kind of probe is used in Southwestern blot? | Labeled oligonucleotide probes |
| What assessed with Flow Cytometry? | Size, granularity, and protein expression of an individual cell |
| In a scatter plot of a flow cytometry, what can be assumed for the cells (dots) in the Lower Left quadrant? | They are negative for both tested labeled antibodies/proteins |
| What are some common conditions for which flow cytometry is often used? | 1. Work up of hematologic abnormalities (paroxysmal nocturnal hemoglobinuria, fetal RBCs in mother's blood) 2. Immunodeficiencies (CD4 cell count in HIV) |
| What is the use of Microarrays? | Profile gene expression levels of thousands of genes simultaneously to study certain diseases and treatments |
| What are some important application of Microarrays? | Genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis |
| Thousands of nucleic acid sequences are arranged in grids on glass or silicon. DNA or RNA probes are hybridized to chip, and scanner detects relative amounts of complementary binding. | Microarrays |
| What is commonly detected with Microarrays? | Single nucleotide polymorphisms (SNPs) and Copy Number Variations (CNVs) |
| What laboratory technique is used to ID presence of a specific antigen or antibody in the patient's blood? | ELISA |
| What technique involves the use of an antibody liked to an enzyme. | ELISA |
| What is more specific, Western blot or ELISA? | Western blot |
| What is detected by a Direct ELISA? | Antigen |
| What is detected by an Indirect ELISA? | Antibody |
| Karyotyping: | Process in which metaphase chromosomes are stained, ordered, and numbered according to morphology, size, arm-length ratio, and banding pattern |
| In which phase does Karyotyping takes place? | Metaphase |
| What is the main use for Karyotyping? | Diagnose chromosomal imbalances |
| What are examples of chromosomal imbalances detected by Karyotyping? | Autosomal trisomies and sex chromosome disorders |
| What is FISH used for? | Used for specific localization of genes and direct visualization of chromosomal anomalies at the molecular level |
| What types of anomalies are visualized with FISH? | Microdeletion, Translocation, and Duplication |
| How is a Microdeletion depicted by FISH? | NO florence on a chromosome compared to fouchtre dat the same locus on the second copy of the chromosome |
| Translocation by FISH demonstrates: | Floucerence signal that corresponds to one chromosome found in a different chromosome |
| Second copy of a chromosome, resulting in a trisomy or tetrasonomy, describes: | Duplication seen with FISH |
| What is the first step in molecular cloning? | Isolate eukaryotic mRNA (post-RNA processing) of interest. |
| Overall, what is the cloned DNA? | That DNA material produced from surviving bacteria after the integration of recombinant plasmid and grow in antibiotic medium |
| What are the Transgenic strategies in mice? | 1. Random insertion of gene into mouse genome 2. Targeted insertion or deletion of gene through homologous recombination with mouse gene |
| What is another way to refer to a Random insertion of a gene? | Constitutive |
| Targeted insertion into a gene is known as _________________. | Conditional |
| Knock-out refers, in terms of gene expression modifications? | Removing a gene, taking it out |
| Inserting a gene in gene expression, can be addressed as ___________. | Knock-in |
| How does the Cre-lox system works? | Can inducibly manipulate gene at specific developmental points |
| What is RNA interference? | dsRNA is synthesized that is complementary to the mRNA sequence of interest. When transfected into human cells, dsRNA separates and promotes degradation of target mRNA "knocking down" gene expression |
| What is codominance? | Both alleles contribute to the phenotype of the heterozygote |
| Genetic condition in which the two alleles of a heterozygote are presented in the phenotype. | Codominance |
| Variable expressivity: | Patients with the same genotype have varying phenotypes |
| What are some examples of Codominance? | 1. Blood groups A, B, AB 2. Alpha 1-antitrypsin deficiency 3. HLA groups |
| The mild or varying differences in phenotype in persons with the same disease is known as ______________________________. | Variable expressivity |
| What would be the genetic term used for two people with exact same condition but different severity of the disease? | Variable expressivity |
| The fact not all the times of a gene mutation can cause the probable disease or condition is referred as: | Incomplete penetrance |
| What is Incomplete penetrance? | Not all individuals with a mutant genotype show the mutant phenotype. |
| What equation is used to predict the risk of expressing phenotype? | % penetrance x probability of inheriting genotype |
| One gene contributes to multiple phenotypic effects | Pleiotropy |
| What is Pleiotropy? | Genetic phenomenon one gene generates multiple or various different phenotypic effects |
| Why is PKU is an example of Pleiotropy? | Manifest with 1. light skin, 2. Intellectual disability, and 3. musty body odor. |
| What is anticipation? | Increased severity or earlier onset of disease in succeeding generations |
| What is a common example condition of anticipation? | Huntington disease |
| Trinucleotide repeat diseases often are associated with which genetic phenomenon? | Anticipation |
| What is Loss of Heterozygosity? | If a patient inherits or develops a mutation in tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops |
| Which type of genes express Loss of Heterozygosity principle? | Tumor suppressor genes |
| Is it possible to observe the principle of Loss of Heterozygosity in oncogenes? | Not possible |
| Conditions that present Loss of Heterozygosity? | Retinoblastoma and the "two-hit hypothesis", Lynch syndrome (HNPCC), and Li-Fraumeni syndrome |
| When is Dominant negative mutation presented? | A heterozygous produces a nonfunctional altered protein that also prevents the normal gene product from functioning |
| A altered protein (nonfunctional) that also prevents normal genes/proteins from working. | Dominant negative mutation |
| What is Linkage disequilibrium? | Tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance |
| A change in tendency in a population is referred in genetic principle as ________________________________. | Linkage disequilibrium |
| What are the two main types of Mosaicism? | 1. Somatic 2. Gonadal |
| Presence of genetically distinct cell lines in the same individual | Mosaicism |
| What is Somatic mosaicism? | Mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs |
| What is another term used for gonadal mosaicism? | Germline mosaicism |
| Mutation only in egg or sperm cells | Gonadal (germline) mosaicism |
| When is encourage to suspect Gonadal mosaicism? | If parents and relatives do not have the disease |
| What is a very common example of a condition presenting with Mosaicism? | McCune-Albright syndrome |
| What condition is due to mutation to G-protein signaling? | McCune-Albright syndrome |
| How is possible to have a non-lethal McCune-Albright syndrome patient? | If the condition presents mosaicism as the mutation occur after fertilization |
| Mitotic errors after fertilization affecting multiple tissues or organs? | Somatic mosaicism |
| What is Locus heterogeneity? | Mutations at different loci can produce a similar phenotype |
| What is a common example of Locus heterogeneity? | Albinism |
| Mutations at different loci causing the same disease | Locus heterogeneity |
| What is Allelic heterogeneity? | Different mutations in the same locus produce the same phenotype |
| In locus (X), there are 3 different mutations, which produce the same disease. This genetic principle is known as: | Allelic heterogeneity |
| B-thalassemia is a condition presting which genetic principle? | Allelic heterogeneity |
| What is Heteroplasmy? | Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease |
| Which type of inheritance always presents with Heteroplasmy? | Mitochondrial inheritance |
| Heteroplasmy gives rise to another genetic principle which is _______________. | Variable expression |
| What is Uniparental disomy? | Offspring receives 2 copies of a chromosome from 1 parent and no copies fro the other parent. |
| What is indicated by Heterodisomy? | Meiosis I error |
| Which form of disomy is due to a Meiosis II error? | Isodisonomy |
| When should a UPD (uniparental disomy) be suspected? | Individual with a recessive disorder when only one parent is a carrier |
| What are the two most common examples of UPD? | Prader-Willi and Angelman syndromes |
| What are the assumptions of the Hardy-Weinberg Law? | 1. No mutation occuring at the locus 2. Natural selection is not occuring 3. Completely random mating 4. No net migration 5. Large population |
| What is the equation of the sum of frequencies in H-W law? | (p)2 + 2pq +(q)2 = 1 |
| What is the frequency of X-liked recessive disease in males? | q |
| What is the frequency of X-linked recessive disease in females? | q2 |
| Definition of Imprinting. | One gene copy is silenced by methylation, and olvy the other copy is expressed --> parent-of - origin effects |
| When does Prader-Willi syndrome occurs? | When paternal allele is deleted or mutated |
| Which condition is seen with maternally derived genes silenced? | Prader-Willi syndrome |
| What are the signs and symptoms seen in Prader Willi syndrome? | Hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia |
| Which chromosome is affected in Prader-WIlli syndrome? | Chromosome 15 of paternal origin |
| Which gene is silenced in Angelman syndrome? | Paternally derived UBE3A |
| Disease occurs when the maternal alleles is deleted or mutated. Dx? | Angelman syndrome |
| What are the signs and symptoms of Angelman disease? | Seizures, Ataxia, severe intellectual disability, inappropriate laughter |
| Which is the involved chromosome in Angelman syndrome? | UBE3A on maternal copy of chromosome 15 |
| Maternal uniparental disomy. Dx? | Prader-Willi syndrome |
| Paternal uniparental disomy. Dx? | Angelman syndrome |
| What mode of inheritance is seen with defects in structural genes? | Autosomal Dominant |
| What are some genetic principles strongly associated with Autosomal dominant mode of inheritance? | 1. Pleiotropic 2. Variably expressive |
| One affected parent of an autosomal dominant condition, has _____% of children affected. | 50 |
| 2 carries of an Autosomal recessive disorder produced (Offspring): | - 25% will be affected (homozygous) - 50% will be carriers - 25% no carriers and unaffected |
| Enzyme deficiencies are often due to what type of mode of inheritance? | Autosomal recessive |
| Which are more severe conditions, autosomal dominant or autosomal recessive? | Autosomal recessive |
| What is the probability of an unaffected individual to be a carrier, if he or she has an affected sibling? | 2/3 |
| What is a common increased risk for autosomal recessive disorders? | Consanguineous families |
| What kind of inheritance mode has no male-to-male transmission? | X-linked recessive |
| What chance (%) sons of heterozygous mothers have of being affected with an X-linked recessive disease? | 50% |
| X-linked recessive usually are more severe in ____________. | Males |
| A female needs to be ___________________, for an X-linked recessive condition in order to be affected. | Homozygous |
| X-linked recessive inheritance pattern ______________ generations. | Skip |
| What are common examples of X-linked dominant disorders? | Fragile X syndrome, Alport syndrome, and Hypophosphatemic rickets |
| Mother affected with an X -linked dominant disorder has: | Transmission to 50% of daughters and sons |
| Fathers tramnit to ___________ daughters in a X-linked dominant inheritance pattern. | ALL |
| What is a commonly used Mitochondrial Inheritance condition? | Leber hereditary optic neuropathy (LHON) |
| Which parent is the only one that can transmit a Mitochondrial inheritance disease? | Mother |
| How many offspring of an affected mother with an Mitochondrial inheritance disease, are affected? | All offspring |
| Why is the variable expression in Mitochondrial inheritance diseases? | Due to Heteroplasmy |
| What is often seen in Mitochondrial myopathies? | Myopathy, lactic acidosis, and CNS disease; secondary to failure in oxidative phosphorylation |
| What is a common biopsy finding in MELAS syndrome? | "ragged red fibers" |
| What gives MELAS syndrome bx findings it "ragged red fiber" look? | Accumulation of diseased mitochondria in the subsarcolemmal of the muscle fiber |
| Cell death of optic nerve neurons ---> subacute bilateral vision loss in teens/young adults (permanent damage). Dx? | Leber hereditary optic neuropathy |
| List of Autosomal Dominant diseases: | 1. Achondroplasia 2. ADPKD 3. Familial adenomatous polyposis (FAP) 4. Familial Hypercholesterolemia 5. Hereditary Hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) 6. Hereditary spherocytosis 7. Huntington disease 8. Li-Fraumeni syndrome 9. Marfan syndrome 10. MEN 11. Myotonic muscular dystrophy 12. NF type I and type II 13. Tuberous sclerosis 14. von Hippel-Lindau disease |
| What are the MC Autosomal recessive disorders? | 1. Oculocutaneous albinism 2. ARPKD 3. Cystic fibrosis 4. Friedreich ataxia 5. Glycogen storage diseases 6. Hemochromatosis 7. Kartagener syndrome 8. Hurler disease 9. PKU 10. Sickle cell anemia 11. Sphingolipidoses (except Fabry disease) 12. Thalassemias 13. Wilson disease |
| Which sphingolipidoses disease is not AR inheritance? | Fabry disease |
| What is the defect in Cystic Fibrosis? | CFTR gene on chromosome 7; commonly a deletion of Phe508 |
| Which is the most common lethal genetic disease of Caucasian population? | Cystic fibrosis |
| What is the role of the CFTR? | Encodes an ATP-gated Cl- channel that secretes Cl- in lungs and GI tract, and reabsorbs Cl- in sweat glands |
| In Cystic fibrosis, the CFTR mutation causes? | Misfolded protein --> protein retained in RER and not transported to cell membrane, cause a decrease in Cl- secretion |
| The misfolded CFTR protein causes electrolytic imbalance in CF because: | Protein is retain in RER and it cannot be transported to cell membrane, leading to retention of Cl-. |
| Increased Cl- concentration in pilocarpine-induced sweat test is diagnostic of: | Cystic fibrosis |
| MCC of recurrent pulmonary infections in a child with Cystic fibrosis? | S. aureus infection |
| What is the most common infectious agent causing recurrent pulmonary infections in adults with CF? | P. aeruginosa |
| What is the described pattern in CXR of CF patient? | Reticulonodular pattern; Opacification of sinuses |
| What are some respiratory complications or associated conditions of Cystic fibrosis? | Recurrent pulmonary infections, allergic bronchopulmonary aspergillosis, chronic sinusitis and bronchiectasis |
| What are the GI complications seen with Cystic Fibrosis? | Pancreatic insufficiency, malabsorption with steatorrhea, fat-soluble vitamin deficiencies, biliary cirrhosis, and liver disease |
| Absence of vas deferens, MCC of infertility in males with: | Cystic fibrosis |
| What treatment is used in CF in order to facilitate mucus clearance? | Chest physiotherapy, albuterol, aerosolized dornase alfa (DNAse) and hypertonic saline |
| Why is azithromycin used in CF treatment? | Anti-inflammatory |
| What can be used to slow the progression of CF pathogenesis? | Ibuprofen |
| In CF patients with Phe508 deletion, what are the treatment options? | Combination of Lumacaftor and Ivacaftor |
| What is X-inactivation (lyonization)? | One copy of female X chromosome forms a transcriptionally inactive Barr body |
| List of X-linked recessive disorders: | 1. Ornithine transcarbamylase deficiency, 2. Wiskott-Aldrich syndrome, 3. Ocular albinism, 4. G6PD deficiency, 5. Hunter syndrome, 6. Bruton agammaglobulinemia, 7. Hemophilia A and B, 8. Lesch-Nyhan syndrome, 9. Duchenne (and Becker) muscular dystrophy |
| Why are female carriers of an X-recessive disorder are variably affected? | It depends on which X chromosome was inherited (mutant vs normal) |
| What are 3 common Muscular dystrophies? | Duchenne, Becker, and Muscular dystrophy |
| Duchenne muscular dystrophy is due to _______________ mutation, leading to ________________ protein. | Frameshift; truncated or absent dystrophin |
| What is the mutated protein in Duchenne muscular dystrophy? | Dystrophin |
| How is the muscular weakness in Duchenne progresses? | Begins at Pelvic girdle muscles and moves superiorly. |
| What is a very common leg sign of Duchenne muscular dystrophy? | Pseudohypertrophy of calf muscles |
| Why is there pseudohypertrophy in calf muscles in Duchenne? | Fibrofatty replacement of muscle |
| What is the MCC of death in children younger than 5 years old with Duchenne muscular dystrophy? | Dilated cardiomyopathy |
| Which is the largest protein-coding human gene? | Dystrophin gene (DMD) |
| What is the main action of dystrophin? | Helps anchor muscle fibers, primarily skeletal and cardiac muscle |
| The loss of dystrophin leads to ----> | Myonecrosis |
| What are two labs results commonly elevated in Duchenne muscular dystrophy? | CK and aldolase |
| Gowers sign. Dx? | Duchenne muscular dystrophy |
| Patient uses upper extremities to help stand up. Sign? | Gowers sign |
| Non-frameshift deletions in dystrophin gene. Dx? | Becker muscular dystrophy |
| What is the nucleotide repeat of Myotonic dystrophy? | CTG |
| What are the clinical features of Myotonic dystrophy? | 1. Myotonia 2. Muscle wasting 3. Cataracts 4. Testicular atrophy 5. Frontal balding 6. Arrhythmia |
| What is Rett syndrome? | Sporadic disorder seen almost exclusively in girls |
| What are clinical manifestations of Rett syndrome? | REGRESSION in motor, verbal, and cognitive abilities; ataxia; seizures; growth failure; and stereotyped hand-wringing. |
| What condition is often associated with regression complications? | Rett syndrome |
| De novo mutation of MECP2 on X chromosome. Dx? | Rett syndrome |
| What is the mode of inheritance of Fragile X syndrome? | X-linked dominant |
| CGGn. Dx? | Fragile X syndrome |
| Trinucleotide repeat in FMR1 gene --> Hypermethylation. Dx? | Fragile X syndrome |
| What is the second most common cause of mental deficiency? | Fragile X syndrome |
| Common features of Fragile X syndrome? | Post-pubertal macroorchidism, long face with a large jaw, autism, and MVP. |
| What are the Trinucleotide repeat expansion diseases? | 1. Huntington disease 2. Myotonic dystrophy 3. Fragile X syndrome 4. Friedreich ataxia |
| CAGn. Dx? | Huntington disease |
| GAAn. Dx? | Friedreich ataxia |
| CTGn. Dx? | Myotonic dystrophy |
| What genetic principle is seen with Trinucleotide repeat expansion diseases? | Anticipation |
| Common autosomal trisomies? | Down, Edwards, and Patau syndrome |
| Trisomy 21. | Down syndrome |
| Trisomy 18 | Edwards syndrome |
| Trisomy 13 | Patau syndrome |
| Down syndrome common clinical features | Intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung disease, congenital heart disease, and Brushfield spots |
| What is the most common GI pathological features of Down syndrome? | Duodenal atresia and Hirschsprung's disease |
| Prominent epicanthal folds. Dx? | Down syndrome |
| What is epicanthal fold? | Skin fold of the upper eyelid covering the inner corner of the eye |
| What neurodegenerative condition is strongly associated with Down syndrome? | Early-onset Alzheimer disease |
| What hematologic malignancies are seen with higher recurrence in Down syndrome patients? | ALL and AML |
| What are the 5 A's of Down syndrome? | 1. Advanced maternal age 2. Atresia (duodenal) 3. Atrioventricular septal defect 4. Alzheimer disease (early onset) 5. AML/ALL |
| What is the most common cause of Down syndrome? | Meiotic nondisjunction |
| What is the mnemonic used to describe the clinical findings of Edwards syndrome? | PRINCE |
| What does PRINCE (mnemonic for Trisomy 18) stands for? | Prominent occiput, Rocker-bottom feet, Intellectual disability, Nondisjunction, Clench fists, low-set Ears, |
| Which trisomy is seen with micrognathia? | Edwards |
| What is the meaning of of micrognathia? | Small jaw |
| What are characteristic clinical findings of Patau syndrome? | Rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, Polydactyly, cutis aplasia, congenital heart disease, Polycystic kidney disease |
| Holoprosencephaly and microcephaly are common severe findings of _________________ syndrome. | Patau |
| Cleft lip/palate, Polydactyly, cutis aplasia, and microphthalmia are often seen with ______________________ syndrome. | Patau |
| If the nondisjunction occurs in Meiosis I, what is the total number of Trisomies produced? | 2 |
| If the nondisjunction happens during Meiosis II, how many trisomies are produced by the end of meiosis II? | 1 |
| n + 1 = | Trisomy |
| n - 1 = | Monosomy |
| How many trisomies and monosomies are produced in meiosis with a nondisjunction problem at Meiosis I? | 2 pairs of each |
| Which trisomy syndrome has all normal serum markers in the 2nd trimester? | Patau syndrome |
| Down syndrome serum marker in the 1st trimester shows an elevated __________________ level. | B-hCG |
| Edwards syndrome has all ___________________ serum markers. | Decreased |
| Examples of chromosome 3 genetic mutation: | von Hippel-Lindau disease and Renal cell carcinoma |
| Chromosome 4 mutations cause: | ADPKD due to PKD2, achondroplasia, and Huntington disease |
| Achondroplasia is due to a mutation in chromosome ___. | 4 |
| Which chromosome is mutated/defective in Huntington disease? | Chromosome 4 |
| What are common conditions due to chromosome 5 defects? | Cri-du-chat syndrome, and Familial adenomatous polyposis (FAP) |
| Hemochromatosis is due to a defective chromosome ___. | 6 |
| What are two conditions due to defective chromosome 7? | Williams syndrome and Cystic Fibrosis |
| What is the most common disease due to a mutation in chromosome 7? | Cystic fibrosis |
| Friedreich ataxia and Tuberous sclerosis are due to a ___________________________. | Chromosome 9 mutation |
| Examples of Chromosome 11 genetic conditions: | Wilms tumor, B-globin gene defects (SCD, B-thalassemia), and MEN 1. |
| Defective chromosome 13 produces: | 1. Patau syndrome 2. Wilson disease 3. Retinoblastoma (RB1) 4. BRCA2 |
| Imprinting conditions are due to a defect in chromosome ____. | 15 |
| Marfan syndrome is due to a defect in chromosome _____, which produces a defective ______________ (protein). | 15; fibrillin |
| Prader-Willi syndrome and Angelman syndrome are both due to a defect in which chromosome? | 15 |
| Alpha-thalassemia is due to chromosome ____ defect, and B-thalassemia is due to a chromosome _____ defect. | 16------alpha 11-------beta |
| Common conditions of mutated chromosome 16: | ADPKD due to PDK1 gene mutation, a-goblin gene defects, and Tuberous sclerosis (TSC2) |
| NF type 1, BRCA 1, and p53, all associated with which defective chromosome? | 17 |
| Genetic disorders caused by Chromosome 22 deficit? | NF type 2, and DiGeorge syndrome |
| 22q11. | DiGeorge syndrome |
| Which are common X chromosome genetic conditions? | Fragile X syndrome, X-linked agammaglobulinemia, Klinefelter syndrome (XXY) |
| XXY. Dx? | Klinefelter syndrome |
| What chromosomes are often associated with Robertsonian translocations? | 13, 14, 15, 21 and 22 |
| When does a Robertsonian translocation occurs? | When the long arms of 2 acrocentric chromosomes fuse at the centromere ant he 2 short arms are lost |
| What happens to the 2 short armes involved in a Robertsonian translocation? | They are lost |
| What are acrocentric chromosomes? | Chromosomes with centromeres near their ends |
| What is the result of unbalanced Robertsonian translocations? | Miscarriage, stillbirth, and chromosomal imbalance (Down and Patau syndromes) |
| Which trisomies are (rarely) due to Robertsonian translocations? | Patau and Down syndromes |
| Cry of a cat. Dx? | Cri-du-chat syndrome |
| Congenital deletion of short arm of chromosome 5. Dx? | Cri-du-chat syndrome |
| Cri-du-chat syndrome may be represented as: | 46, II or XY, 5p- |
| What is the most characteristic finding of Cri-du-chat syndrome? | High-pitched crying/meowing |
| Congenital microdeletion of long arm of chromosome 7. Dx? | Williams syndrome |
| The elastin gene is deleted in which genetic condition of defective chromosome 7? | Williams syndrome |
| What is the adjective use to describe the facial features of a patient with Williams syndrome? | "elfin"facies |
| What are some key clinical features of Williams syndrome? | 1. Distinctive "elfin" facies 2. Hypercalcemia (increased sensitivity to Vitamin D) 3. Well - developed verbal skills 4. Extreme friendliness with strangers, 5. CV problems |
| What CV conditions are seen with Williams syndrome? | Supravalvular aortic stenosis and Renal artery stenosis |
| What does an "elfin" facies referred to? | Face characteristic associated with elve-looking face |
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