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Molecular Biology
flashcards for pharmacy school molecular biology
| Question | Answer |
|---|---|
| organogensis | the growth and reproduction of cells |
| cell cycle arrest | cell doesn't grow if function error is detected at the check point |
| apoptosis | programmed cell death |
| 3 ways to control cell proliferation | cycle arrest, apoptosis, and DNA repair |
| what is at each cycle check point> | promoters or inhibitors of the cell cycle |
| P53 | guardian of the genome |
| if transcription factors get out of the cell, what does this signal? | problem with cell's DNA |
| necrosis | non-programmed cell death, leads to a release of toxins |
| process of apoptosis | chops DNA into small packages rather than a smear, chopped at the histones |
| intracellular signal process that starts apoptosis | stress-> cytochrome c -> production of enzymes -> apoptosis |
| replication fork | the point where two strands of DNA are pulled apart to that replication can occur |
| DNA is replicated in this direction only | 5' to 3' |
| lagging strand | short strand of 5'-3' strands that form on the 3' to 5' strand |
| ligase | puts the short fragments of DNA together with phosphodieester bond |
| helicase | unwinds DNA |
| primer synthesis | primase |
| DNA synthesis | DNA polymerase |
| un-supercoils DNA | topoisomerase |
| DNA has repair mechanisms because | it is in an oxidizing environment and replication is never error free |
| DNA repair process | send in complex, assemble large protein, cut out damaged DNA, replace sequence, DNA is fixed |
| drugs the inhibit DNA replication can be used for: | anti-cancer |
| inhibitors of DNA replication include: | alkylating agents and anti-metabolites |
| alkylating agents | cross link two DNA strands so they can't be replicated (examples: cyclophosphamide, chlorabucil, BCNU, thiotepa) |
| anti-metabolites | have affinity for enzymes of nucleic acid biosynthesis (false building blocks) examples: aminopterin, methotrexate, 5-fluorourcil, mercaptopurine) |
| draw-back of inhibitors of DNA replication | non-specific for DNA damaged, attack all rapidly dividing cells non-descriminately |
| prototype of alkylating agents | nitrogen mustard |
| new generation inhibitor of DNA replication | topoisomerase inhibitor which blocks the un-supercoiling |
| type 1 inhibited by | irinotecan and topotecan |
| type 2 inhibited by | etoposide and teniposide |
| methorexate suppresses immune cell proliferation (example: MTX, Rheumatrex) | used in Rheumatoid arthritis |
| phenotype | which allele is express--dominant allele vs recessive allele |
| blood type | shows codominance |
| segregation | getting 1 gene at random from each gene pair |
| independent assortment | Mendel's Law applied to 2 gene rather than 1 (9AB, 3Ab, 3aB, 1ab) |
| genetic linkage | genes on the same chromosome are inherited together |
| recombination frequency formula | # of gametes with new genetic combinations/total # of genes |
| recombination frequency increases when | the distance between 2 genes on the same chromosome increases |
| linkage disequilibrium | non-random association between 2 alleles at distinct loci on the same chromosome (a group of close alleles may stay the same even with the recombination) |
| 4 unique patterns of inheritance | x-linked disorders, y chromosomal inheritance, mitochondrial DNA and genetic imprinting |
| x linked disorders: | 1 recessive allele produces phenotype, fathers never transmit alleles to son, half of sons are affected, half of daughters are carriers, |
| y-chromosomal inheritance | paternal inheritance, every son recieves allele from father, daughters not affected or carriers |
| mitochondrial DNA | only affect women, all sons and daughters affected, men don't pass it on, |
| genetic imprinting | gene silenced thru DNA methylation |
| examples of gene imprinting | prader-willi syndrome and angelman syndrome |
| autosomal dominant | every generation shows the disease in men and women |
| autosomal recessive | lots of carriers, only disease (sometimes) with offspring of 2 carriers |
| multigenic disease | disease state depends on more than one gene (examples: heart disease, HTN, most psychiatric disorders) |
| single gene disorders can appear multigenic, but we can predict these! | g6pd-deficiency and hemochromatosis |
| quantitative trait loci | are DNA regions that contribute to complex phenotypes (continuous traits which show bell shaped distributions) |
| recombination | rearrangement of DNA sequences for variation of species and immune diversity |
| recombination can be problematic because | a single mutation can cause disease |
| mutation | permanent change in the DNA base sequence |
| mutations in germ cells are | transmitted to offspring |
| somatic mutations | lead to symptoms, but not transmitted to offspring |
| damage to DNA that can result in mutation | oxidative metabolism, spontaneous depurination, errors in DNA replication |
| Types of Mutations | gene amplification or deletion, deletion of functional domains, point mutations, frame shifts, chromosome translocation |
| point mutation | can be silent, neutral, missense (functional consequences) or nonsense (codes for STOP codon) |
| frame shift | messes up entire chain, can lose protein that was supposed to be made AND code for disease protein |
| chromosome translocation | cross-over between 2 genetic loci |
| polymorphisms on the same strand of DNA | are in complete linkage disequilbrium |
| haplotype | pattern of linked polymorphic sites |
| single nucleotide polymorphisms (SNP) | occurs about once every 300 base pairs |
| SNP's can cause: | changes in protein sequences, gene expression, altered intron splicing, RNA instability, change in junk DNA |
| repetitive sequences | used as diagnostic markers in genetic disease and forensic investigation |
| tandom repeats | multiple copies of specific sequences next to each other |
| transposable elements (transposons) | repetitive sequences scattered in genome |
| microsatellites | 2-4 nucleotides repeated a variable number of times |
| penetrance | detectable manifestions of the trait encoded by a gene (the frequency of expression of a genotype) |
| non-penetrance | no genotype expression |
| basic genetic determinants | genetic predispostion in the host and pathogen genomics (virulence and anti-ionfective resistance) |
| genetic predisposition (how we mount a response) | based on our polymorphisms |
| TH1 | slower response- defends against viruses, T lymphocyte response |
| TH2 | faster response- protects from bacteria- uses B cells |
| transposons can generate disease by: | exchange or jumping around |
| MHC- major histone compatibility | determine "self" and how we respond to disease |
| toxicogenomics | genetic deficiency (isonaicid toxicity and primaquine toxicity) |
| HIV dur resistance | occurs b/c mutations cluster (where selective pressure is occuring from drugs) and transfer drug resistance |
| use combination chemotherapy for AIDS | overcomes clustering and resistance |
| HAART | maximize effect with minimal SE, nucleoside analogs, protease inhibitors, reverse transcriptase inhibitors |
| fusion inhibitor | chemokines that block HIV virus from entering thru cell receptors |
| SKY (spectral karotyping) | detects chromosome breakage, translocations, inversions (used in leukemia) |
| polymerase chain reaction | doubles DNA every cycle, amplify any gene and look for disease, mutations or markers |
| efficiency of DNA amplification depends on | primers...too much G-C and primer binds too strong, too much A-T and primer won't stick, causes mispairing |
| DNA sequencing with the Sanger method | breaks up DNA and determines base pairing after electrophoresis |
| expressed sequence tags (EST's) | can screen the genome looking for a specific snippit of DNA, can form EST libraries with known tags |
| RNA screening can occur through | microarray, differential display, and serial analysis of gene expression (SAGE) |
| microarray | take gene sequences, spot onto array, extract RNA, reverse to DNA, label red and green, if gene not expressed it won't show up |
| proteomic analysis (gel electrophoresis) | IEF= separation by charge characteristics and SDS-Page= separation by molecular mass |
| pharmacogenomics | the whoole genome application of pharmacogenetics |
| pharmacogenetics | examines the single gene interactions with drugs |
| pharmacogenomics is moving towards | the effects of genetic makeup on kinetics and dynamics |
| goals of genomics | target specific populations with enhanced efficacy, reduce toxicity and reduce attrition costs |
| phase 1 (trials) | determine safety on healthy volunteers (low dose) |
| phase 2 (trials) | looking for effectiveness and adverse effects |
| phase 3 (trials) | check effectiveness and check for ADR from long-term use |
| phase 4 (trials) | post marketing testing |
| phase 3 example- | tranilast-didn't cause hyperbilirubinism cause by random polymorphism |
| genostratification | use of genetic tests to determine patient enrollment |
| some "allergies" are actually | a polymorphism which causes self vs non-self immune response |
| benefits of pharmacogenomics | assessment of disease predispostion and determinatin of drug responses |
| with genetic test we can | identify true positives (sensitivity) and true negatives (specificity) |
| can use genomic signatures to | guide the use of chemotheraputics |
| large scale screening techniques are central to: | pharmacogenomics |
| drug target | any gene product involved in the pharmacologic action of a drug |
| drug targets include | protein targets (receptors, enzymes), proteins in signal transduction, proteins assoc. with disease risk, proteins assoc. with toxicity |
| drug target pharmacogenetics | the contribution of genetic variability in drug targets to either variable drug effacacy or variable drug toxicity |
| goal of drug target pharmacogenetics | adjustment of drug therapy based on individual genetic makeup |
| common drug targets with unique features: | GPCR, kinases, steroid receptors |
| targeting in infectious disease | pathogen derived |
| theranostics | development of diagnostic tests directly linked to theraputic applications |
| in breast cancer (theranostic test) | HercepTest |
| theranostics will help | determine if an individual should be treated with that drug and at what dose |
| to cells, total equilibrium means | death |
| in human gene there are ?? genes that code for transport proteins | 500-1200 |
| 2 basic groups of drug transporters | efflux and uptake |
| efflux transporters | contribute to multi-drug resistance, belong to ABC family, prevent toxins from entering vital organs |
| ABC (stands for) | ATP binding cassette |
| ABC transporters | have evolved to defend calls, have suubfamilies A-G |
| ABCB1 | efflux in cancer cells, tamoxifen/progesterone inhibit |
| ABCC (MRP's) | transport organic anions, provide protection at important barrier organs, |
| ABCG2 | forms dimers to transport, expressed in placenta, liver, GI, lungs and kidneys |
| ABCB1 (importance) | may be the most important efflux transporter |
| ABCB1 substrates | anticancer drugs, cardiac drugs, HIV protease inhibitors, immunosuppressants, antibiotics and antihistamines. also hormones and lipids |
| ABCB1 and protease inhibitors | causes variable bioavailability |
| disease caused by defect in efflux transporter | Dubin-Johnson syndrome-- MRP2 variation causes jaundice |
| uptake transporters include | organic cation transporters, anion transporters, and nucleotide transporters |
| organic cation transporters | uptake of cations into liver, kidneys, brain (NT's) |
| organic anion transporters | uptake of bile acids, also in liver, kidneys, brain |
| nucleotide transporters | can be expressed in tumors, |
| disease cause by defect in uptake transporters | primary canitine deficiency |
| in the brain (BBB) transporters consist of | mostly efflux transporters to pump stuff out |
| at the blood-testes barrier | OCT1, OCT3, OCTN1 and OCTN2 allow only selective transmission |
| transfer into the placenta | mostly passive diffusion |
| polymorphisms in CYP can occur by | frameshift, insertions, splicing defect, gene deletion |
| increase in CYP occurs by | gene duplication |
| a method of genotyping before dosing | AmpliTaqP450 |
| flavin mono-oxygenases | catalyze the oxygenation of nucleophilic hetero-atom containing xenobiotics |
| characteristics of cancer | excessive growth, extension of life span (of cell), metastasis formation, tumor-host interactions |
| repilcative senescence (how cells age) | chromosome ends shorten with each cell division until cell stops dividing |
| telomerase | replenishes chromosome ends and lengthens cell life span (should be only in germ and stem cells) |
| cancer from telomerase | reactivated telomerase in normal differentiated cells (should be turned off) |
| metastasis | mimics movement of white blood cells |
| angiogenesis | once a tumor gets to a certain size, new blood vessels are needed for further growth |
| immune system and cancer | chronic inflammation can cause DNA damage which leads to cancer |
| 3 pillars of current cancer therapy | chemotherapy, surgery, radiation therapy |
| classes of anti cancer drugs | alkylating agents, anti-metabolites, antibiotics, alkaloids |
| antibiotics in cancer therapy | generate free radicals, stack b/w DNA bp, interfere with topoisomerase |
| alkaloids in cancer therapy | inhibit mitosis |
| molecular targets specific for cancer cells (rather than people cells) | antigens from oncoviruses, mutations in cancer-related genes, translocations for oncogenes, alternative transcripts, post-translational modifications, selectively expressed oncogenes, idiotypes |
| oncogene kinase inhibitor | GLEEVEC--highly specific for kinases not critical to humans only cancer) |
| a cancer antibiotic | herceptin |
| a more useful cancer therapy | use combination therapy like in HIV therapy |
Created by:
bentlere
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