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FA complete review

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
Created by: rakomi
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