Term
| What is important about knowing DNA sequence? |
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Definition
1. Important for tx options
2. provides rational basis for tx outcomes
3. Comparison between individuals & species may allow better understanding of disease mechanisms |
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Term
| Distinct diff between humans and chimps |
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Definition
| 35 mill single nucleotide changes, 5 mill insertions/deletions changes, various chromosomal rearrangements |
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Term
| What is important about CMP-N-acetylneuraminic acid hydroxylase (CMAH) ? |
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Definition
| Activity of this enzyme is ABSENT in humans |
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Term
| What does CMAH become? Where the product found? |
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Definition
CMP-Neu5Ac[Neu5Ac: N-acetylneuraminic acid] -> CMP-Neu5Gc[Neu5Gc: N-glycolylneuraminic acid]
Humans CANNOT complete this conversion
HUMANS CELLS (surface cells) HAVE *** Neu5Ac |
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Term
| What is the difference between human cells and chimps cells regarding the enzyme? |
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Definition
| Humans: Neu5Ac; Chimps: Neu5Gc; in surface of mammalian cells; **these are Sialic acids* |
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Term
| Humans are susceptible to which Plasmodium? Chimpanzees are susceptible to which? How is this related to CMAH? |
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Definition
Humans: Plasmodium falciparum binds to Neu5Ac
Chimps: Plasmodium reichenowi binds to Neu5Gc |
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Term
| Signs we are switching to use DNA for tx? |
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Definition
Hormonal and chemotherapy decisons
Dose of Warfarin (coumadin- genotype |
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Term
| What does the effectiveness of a drug depend on? |
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Definition
| Pharmacokinetics, Pharmodynamics, Pharmacogenomics |
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Term
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Definition
| description & prediction of time- course of drug concentrations in body fluids |
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Term
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Definition
| time course & intensity of drug effects on individuals |
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Term
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Definition
| influence of genetic make up on drug effectiveness |
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Term
| What determines drug effectiveness? What can modify all of these processes? |
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Definition
absorption, distribution, metabolism, excretion
ALL can be modified by: Genetic Background or Polymorphism of Relevant genes/proteins |
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Term
| What does CYP (Cytocrome P450) enxymes Do? |
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Definition
Carry out several reactions including hydroxylation
[hydroxylation=reaction that introduces hydroxyl group (OH) to an organic compound- by oxidation of a substrate] |
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Term
| What occurs with cytochrome P450 (CYP) enzymes in the metabolization of drugs or xenobiotics (synthetic chemical foreign to the body) ? |
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Definition
| CYP enzymes: metabolize: xenobiotics hydroxylated & excreted; CYP mediated reaction OCCURS in Liver, intestine & Lung cells (microsomes)- here is where Activation & Formation of reactive oxygen occurs |
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Term
| What is Cytochrome P450 (CYP) |
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Definition
CYP:
-Family of 150 isoforms
-Notable: CYP3A4, 2D6, 2C9, 2C19, 2E1, 2A6, 1A2
-Exist as multiple alleles in population |
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Term
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Definition
Alleles:
-2 alternative forms of a gene or DNA sequenc in our cells: 2 copies of a gene-maternal & paternal
-2 alterative forms can be identical or not identical
-Homozygous=2 identical alleles
-heterozygous=2 non-identical alleles |
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Term
Define:
Dominant
Autosomal
Sex-linked
Recessive |
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Definition
Dominant: trait/phenotype manifesting in a heterozygote
Autosomal: linked to autosomes
Sex linked- linked to X/Y chromosomes
Recessive: trait/phenotype manifesting in homozygote |
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Term
| What CYP is involved with Coumadin? |
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Definition
-CYP2C9
1.metabolizes more than 100 drugs, including Coumadin
2. >40 alleles
Different Alleles- differ in specific places in their sequences= Single Nucleotide Polymorphism |
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Term
| Coumadin & CYP2C9: How is drug metabolism and effect related to the alleles of CYP2C9? |
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Definition
1. Polymorphism -may alter activity of enzyme which effects drug dose for desired effect
2. Drug gets inactivated faster, then dose needs to be increased to be effective. Metabolism faster=dose incr
3. If it takes too long to inactivate then decrease dosage to protect against excessive bleeding; metabolism slower=dose lowered? |
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Term
| Which CYP2C9 alleles are metabolized faster vs slower? How does this effect bleeding? |
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Definition
CYP2C9*2 or CYP2C9*3 allele= increased bleeding, Metabilize drug slower thus patients need LOWER dose
CYP2C9*1 homozygous patients DO NOT require lower dose; metabolization faster |
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Term
| What inhibits VKORC1 activity? |
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Definition
Vitamin K epoxide reductase (VKORC1) activity is inhibited by Coumadin
VKORC1 -converts Vit K epoxide -> reduced form of Vit K
Factors II, VII, IX, X - Vit K dependent proteins
-VKORC1 polymorphism may modify effectiveness of drug |
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Term
| 6 things about DNA Structure |
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Definition
1. Polymer (polynucleotide)
2. 4 bases (aden. guan. cytos. thym-ine, RNA=uracil
3. 5 carbon sugar
4. NucleoTIDE: nucleotide monophosphates
5. Phosphodiester Bonds: sugar-phosphate (backbone)
6. 2 strands of DNA - held by H-bonds |
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Term
| What does Pure As Gold & Pyr amids are CUT represent? |
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Definition
Adenine (A), Guanine (G)= Purine
Cytosine, Thymine, Uracil = Pyrimidines |
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Term
Nucleoside = ?
Nucleotide = ? |
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Definition
nucleoside = base + sugar ex: adenosine, Deoxycytidine
nucleotide = nucleoside + phosphate ex: ADP, ATP |
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Term
| Where do nucleotides form bonds? |
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Definition
| 5' phosphate of 1 nucleotide forms phosphodiester bond with 3' OH of next nucleotide |
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Term
| 4 functions of Nucleotides & 3 examples of Useful Nucleotides? |
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Definition
Nucleotides: constituents of DNA & RNA, cofactors in enzyme reactions, energy currency, cell signaling (GTP)
EX:
-FAD, NAD (electron carriers
-Cyclic AMP & cGMP (second messengers)
-Coenzyme A (CoA) - Carbon Carrier in Fatty Acid Metabolism |
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Term
| DNA Denaturation: which processes are Zero Order Kinetics vs. Second Order Kinetics? |
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Definition
OH- or Heat- separation of dds= Zero order kinetics
Renaturation: Second Order Kinetics |
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Term
| What does the hyperchromicity Curve of DNA Denaturation Kinetics represent? |
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Definition
-DNA bases aborbe MORE UV light when DDS melts
-SS: linear increase over a temp range
-DD: 2 fold increase around Temp |
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Term
| What effects DNA and How do these variable affect DNA denaturing vs Stabilizing? |
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Definition
Denature: heat- disrupts H-bonds, Chaotropes-changes structure of H20, disrupts H-bonds
Stabilizing helix: Na, K+; GC/AT ratio Increase (more GC=more stable) |
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