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General Principle 2

UWORLD + FA review

Locus Heterogeneity ability of 1 disease or trait to be caused by mutations in multiple different genes
Polyploidy? occurs at times of more than 2 complete sets of homologous chromosomes exits within on organism or cell
What is cytochrome c? it is mitochondrial enzyme that activates caspases and indirectly brings out the cell death through the intrinsic pathway of apoptosis
Cytochrome activates caspases via teh ___________________pathway ______________. Intrinsic Pathway Apoptosis
The initiation phase of apoptosis is divided into what? Intrinsic and Extrinsic Pathway apoptosis
Caspase activation in apoptosis is done during the_________________ phase. Initiation
Medical Interview Open-ended questions are the most effective way to initiate interview
Northern Blotting Detects RNA
Southern blotting Detects DNA
Western blotting Proteins are detected
Southwestern blotting DNA-binding protein
Ras proto-oncogene that codes for a membrane-bound G-protein
Imprinting Phenomenon in which an offspring's genes are expressed in a parent-specific manner
SAM common methyl group donor
Carrier mediated transport Includes: 1. Facilitated diffusion 2. Active trasnport
Piridoxine Vitamin B6
What is a Transamination reaction? occurs between an amino acid and alpha-keto acids.
What are some common alpha-keto acids? 1. Pyruvic acid 2. Oxaloacetic acid, component of TCA cycle 3. Alpha-ketoglutarate
Isoniazid INH
The "fast" or "slow" metabolism of INH causes: A bimodal distribution graph
Volume of distribution (Vd) Hypothetical volume of fluid into which the administer amount of drug would need to uniformly distributed to produced the observed plasma concentration.
Vd levels: Low 3-5 liters
A low Vd: 3-5 liters
A Vd of 14-16 L would suggest: Drug with a small molecular weight but hydrophilic
What is suggested a Vd of 41 L? Drug is small molecular weight and uncharged (lipophilic or hydrophobic)
CYP450 enzymes: Found in liver and responsible for majority of drug metabolism
Polymorphisms: occuring in genes coding for CYP450 enzymes result in various phenotypes that differs in rates of metabolism
Increase levels of IL-1, IL-6 and TNF-a lead to: Increase release levels of acute-phase reactants
Acute phase reactants: Increase their release by increased levels of pro-inflammatory cytokines
Bioavailability: Fraction of administered drug that reaches the systemic circulation
What type of administration decrease the bioavailability? Oral drugs, due been subjected to First-pass metabolism
Rectal drug administration Increased bioavailability
Locus Heterogeneity Familial Hypercholesterolemia
Polyploidy? Hydatidiform male (69 XXX, 69 XXY, 69XYY)
Medical Interview Allow patient to describe the conditions, in their own words.
Northern Blotting single stranded RNA probe
Southern blotting ss-DNA probe
Western blotting Antibody used as probe
Southwestern blotting ds-DNA probe
Ras Activates the MAP kinase pathway and ultimately affects transcription
Ras Does not bind to DNA
Imprinting DNA methylation
Imprinting Methylation of DNA causes "imprinting"/"silencing"/"inactivation" of gene
SAM S-adenosylmethionine
Carrier mediated transport Movement across the membrane depends on carrier proteins in the membrane
Carrier mediated transport Can become SATURATED
Vitamin B6 is a cofactor in amino acid Transamination and Decarboxylation reactions
Isoniazid metabolized by ACETYLATION
Isoniazid Its metabolism depends on the person's ability to metabolize fast or slow
Which kind of people have increased risk of INH toxicity? "Slow" acetylators have increased risk of adverse side effects
Volume of distribution (Vd) (amount of drug given (mg))/ plasma concentration of drug (mg/L))
Vd levels: High 41 L
A low Vd: Drug: - Large molecular weight - Bound extensively to plasma proteins, or, -Highly charged (hydrophilic)
A low Vd: Remains in plasma compartment (approx 3L)
A Vd of 14-16 L would suggest: Drug distributes into interstitial fluid compartment and intravascular compartment
What is suggested a Vd of 41 L? Highly bound to tissues.
What common breast cancer drug is metabolized by the CYP450 system? Tamoxifen
Acute phase reactants: Increased levels leads to INCREASED ESR, leading to quick RBC sedimentation
Acute phase reactants: C-reactive protein, fibrinogen
Rectal administration only bypasses first-pass metabolism if it is: Region below the dentate line, drains directly to systemic circulation.
What ion is responsible for the synchronization of skeletal muscle contraction? Sarcoplasmic calcium
Increased intracellular calcium causes in Skeletal muscle: 1. Activation of PHOSPHORYLASE KINASE ---> stimulating glycogen phosphorylase to increase GLUCONEOGENESIS
What is the effect of increased intracellular ATP in skeletal muscle during contraction? decrease the rate of glycogenolysis upon cessation of active muscle contraction.
Silent mutation base substitution codes for same amino acid
Missense mutation base substitution codes for different amino acid
Conservative mutation base substitution codes for different amino acid with similar chemical structure
Nonsense mutation base substitution introduces premature stop codon
What are the 3 stop codons? 1. UAA (U Are Away) 2. UAG (U Are Gone) 3. UGA (U Go Away)
Nonstop mutation base substitution within a stop codon resulting in continued translation
Infinite translation of an amino acid is due to a ___________ mutation. Nonstop
Splice site mutation Mutation at the splice site alters intron removal form pre-mRNA
What kind of DNA mutation leads to inappropriate intron removal? Slice site mutation
Frameshift mutation Deletion/insertion of bases non-divisible by 3, causes downstream misreading.
What are the main 3 common findings of Down syndrome? Cognitive impairment, Facial deformity, and cardiac defects
What are the 3 main causes of Down syndrome? 1. MC --> MEIOTIC NONDISJUNCTION (95% of cases) 2. Robesonian (unbalanced) translocations 3. Mosaicism
Extra copy of chromosome 21 present in every cell Down syndrome due to Meiotic nondisjunction
What is a risk factor for the MCC of Down syndrome? Advanced maternal age
Unbalanced translocation of chromosome 21 All or part of additional chromosome 21 is ATTACHED to another chromosome
Some (not all) cells have extra chromosome 21; nondisjunction event early in embryonic life. Describes? Down syndrome caused by Mosaicism
Parallel resistance: Used to measure systemic resistance (whole body)
Series resistance: Used to measure resistance in a specific organ
R1+R2+R3 = Total Resistance Series resistance
1/R1 + 1/R2 + 1/R3 = 1/TPR Parallel resistance
What is Beer's Criteria used for? Identify drugs that are to be used carefully in the elderly population
What are some drugs included in the Beer's criteria? 1. Anticholinergic: - 1st generation antihistamines (diphenhydramine) 2. CV: - Alpha-1 blockers, Centrally-acting alpha-2 agonists, and many antiarrhythmics 3. CNS: - TCAs, Antipsychotics, Barbiturates, Benzodiazepines 4. Endocrine: - Long-acting sulfonylureas and sliding scale insulin 5. Pain: - NSAIDs and Skeletal muscle relaxants
What is a common 1st-generation anti-histamine? Diphenhydramine
What receptors are blocked by 1st generation antihistamines? Muscarinic receptors
Mydriasis is caused due to: Paralysis of ciliary muscle and iris sphincter
What are the 3 fates of Pyruvate? 1. Acetyl-CoA by Pyruvate dehydrogenase (AEROBIC) 2. Lactic Acid by Lactate dehydrogenase (ANAEROBIC) 3. Oxaloacetate (involved in gluconeogenesis)
MtDNA Most common non-nuclear DNA found in Eukaryotic cells
Mitochondrial DNA resembles ________________________. prokaryotic DNA and is maternally derived
Leg lymphatics: Medial foot: Bypass the popliteal nodes and goes straight up to the Superficial inguinal nodes Lateral foot: Lateral foot --> Popliteal nodes --> Deep inguinal nodes.
Superoxide Dismutase: anti-oxidant; neutralizes ROS, thus, preventing cell injury
Half-life measure of how quickly a drug with first-order kinetics is eliminated from the body
What is the abbreviation for have life? t 1/2
Half-life = (0.7 x Vd) = ---------------- Clearance (CL)
Half live: 1 ---> 2 ---> 3 ---> 4 ---> 5 ---> Amount eliminated (%) 50% 75% 87.5 % 93.75% 96.875%
DNA pol I in PROKARYOTES has 3 functions: 1. - 5' to 3' polymerase activity 2. - 3' to 5' exonuclease activity 3. - 5' to 3' exonuclease activity
What is the key or unique function (characteristic) of bacterial DNA pol I? 5' to 3' exonuclease activity
What is the function of DNA pol I 5' to 3' exonuclease activity? remove the RNA primer created by RNA primase and repair damage DNA sequences.
What are the main categories of DNA-binding proteins? 1. Transcription factors ( Myc, CREB) 2. Steroid receptors (Cortisol, Aldosterone, Progesterone) 3. Thyroid hormone receptor 4. Fat-soluble vitamins (Vitamin D, retinoic acid) 5. DNA transcription and replication proteins
Multifactorial inheritance complex interaction between numerous genetic and environmental factors to determine phenotypic expression
The phrase " the closer the relative, the higher the chances of inheriting the condition" is descriptive of what mode of inheritance? Multifactorial Inheritance
What are some common conditions of Multifactorial inheritance? Spina bifida, Cleft lip and palate DM, CAD and HTN
Which are the POORLY-vascularized peripheral compartments? Skeletal muscle, bone and fat
Delayed drug distribution is seen in: Poorly vascularized peripheral compartments; Most common are skeletal muscle, bone, and fat.
Initial rapid distribution is seen with: Well ventilated peripheral compartment organs, such as Brain, Liver, Kidney, Lungs and Heart.
Lipophilic drugs: 1. Distributed fast and quickly in well-vascularized organs, but 2. highest distribution is in poorly-vascularized organs
Transcriptional enhancers and silencers localization: May be upstream, downstream, or within a transcribed gene
Transcriptional enhances ---> Increase rate of transcription
Transcriptional silencers --> Decrease rate of transcription
The enhancer sequence: - bind ACTIVATOR proteins that facilitate bending of DNA
What is the effect on DNA bending due to enhancer attachment to an activator protein? Allow for activator proteins to interact with general transcription factors and RNA pol II at the PROMOTER
What are the Eukaryotic promoters and their localization? 1. TATA, or Hogness box ------ 25 bases UPSTREAM 2. CAAT box ------ 75-80 bases UPSTREAM
What are the Prokaryotic promoters and their localization? 1. Pribnow box --- -10 bases upstream 2. 35 element ---- 35 bases ustream (presence indicates very high transcription rate)
Promoter Always located upstream from their associated genes, and functions to initiate transcription
Shine-Dalgarno sequence ribosomal binding site in bacterial mRNA - Located 8 bases upstream for the start codon AUG - Helps to recruit ribosome to the mRNA to initiate protein synthesis
8 bases upstream from start codon AUG Shine-Dalgarno sequence
What start codon is associated with the Shine-Dalgarno sequence? AUG
What is the probability of being a carrier if: Unaffected individual from unaffected parents has a affected sibling of an autosomal recessive disorder? 2/3
What is pleiotropy? Describes were multiple phenotypic manifestations result from a single genetic mutation.
What are some common DNA-binding proteins? c-Jun and c-Fos
Created by: rakomi



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