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101 Cards in this Set
- Front
- Back
- 3rd side (hint)
Chromatin Structure
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negatively charged DNA wrapped around a histone (H2A, H2B, H3, H4), connected by H1.
Condensed = hetero-, inactive Less condensed = eu-, active |
histones
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Nucleotides
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Purines (A, G) large rings
Pyrimidines (C, U, T) small rings PURe As Gold CUT the PY (pie) |
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Eukaryotic DNA polymerases
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alpha - replicates lagging strand, synthesizes RNA primer
beta - repairs DNA gamma - replicates mitochondrial DNA delta - replicates leading strand epsilon - repairs DNA |
5 types
3 for replication 2 for repair |
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DNA repair process
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endonuclease cleaves strand upstream
exonuclease clease strand downstream DNA polymerase Beta fills gap |
3 steps
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DNA repair defects lead to disease
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Xeroderma Pigmentosum (UV light)
Ataxia-Telangiectasia (X-rays) Bloom's syndrome (radiation) Fanconi's anemia (crosslinking agents) |
UV light
X-rays Radiation Crosslinking agents |
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Eukaryotic RNA polymerases
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polymerase I - rRNA
polymerase II - mRNA, snRNPs polymerase III - tRNA no proofreading alpha-amanitin inhibits poly II |
in the order that RNA is needed for translation...
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Start and Stop Codons
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Start
AUG (Are U Going?) Stop UGA (U Go Away) UAA (U Are Away) UAG (U Are Gone) |
1 Start, 3 Stop
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Regulation of Gene Expression
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Promoter - where RNA polymerase/transcription factors bind upstream
TATA (25 bp upstream) CAAT (70 bp upstream) Enchancer - where transcription factors bind to increase expression |
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RNA processing
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1. 5' 7-methyl-guanine cap
stability, mediates translation 2. 3' Polyadenylation stability, mediates nuclear export 3. Splicing out introns for fun? |
3 steps
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tRNA Structure
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75-90 nucleotides
anticodon end is opposite 3' aminoacyl 3' CCA sequence chemically modified bases |
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tRNA charging
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aminoacyl-tRNA synthetase
adds 1 aa to 3' end, using 1 ATP proofreading capability |
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tRNA wobble
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allows many codons to match one tRNA with only the first two bases of it's anticodon
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PCR
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ligate/denature DNA,
add premade specific probes add heat-stable DNA polymerase repeat until DNA sequence is amplified |
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Molecular Biology Techniques
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Southern - DNA probe to find DNA
Northern - DNA probe to find RNA Western - Ab probe to find protein Southwestern - DNA probe for TFs |
Map directions
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ELISA
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labeled Ab/Ag to Ag/Ab in pt sample
used in HIV Sn = Sp = ~100% |
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Inheritance Modes
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Auto Dom - structural genes
M/F affected equally presents after puberty Auto Rec - 25% offspring of carriers enzyme deficiencies present in childhood X-link Rec - 50% sons of hetero mom X-link Dom - all F kids of sick dad M/F kids of sick mom hypophosphatemic rickets Mitochondrial - transmitted by mom all kids may show dz leber's hereditary optic neuropathy mitchondrial myopathies |
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Variable expression
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nature and severity of phenotype varies from one pt to another
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Incomplete penetrance
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Not all individuals with mutant genotype show dz phenotype
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Pleiotropy
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one gene has greater than one effect on phenotype
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Imprinting
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Differences in phenotype depend on whether the mutation is of maternal or paternal origin
Angelmans - maternal transmission Prader-Willi - paternal transmission |
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Anticipation
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Severity of disease worsens or age of onset decreases in successive generations
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Loss of heterozygosity
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if a pt inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops (not true of oncogenes)
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Dominant negative mutation
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exerts a dominant effect because the body cannot produce enough of the normal gene product with only one functioning allele or presence of the altered gene product inhibits the normal product
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Linkage disequilibrium
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two alleles at linked loci occur together more often than probability would suggest.
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Hardy Weinberg population genetics
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assumes no migration, no mutation, no natural selection, no mating preferences
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Down Syndrome
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mental and growth retardation
trisomy 21 tested with karyotyping 1:800 increased risk with maternal age decreased AFP in amniotic fluid polyhydramnios |
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Fragile X
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mental retardation
characteristic facial features large testes X-linked failure to express RNA binding protein |
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Sickle cell anemia
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recurrent painful crises
autosplenectomy -> imm def autosomal recessive 1 missense mutation in beta globin 1:400 Af-Am |
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Cystic fibrosis
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recurrent pulmonary infections
exocrine pancreas insufficiency infertility autosomal recessive mutated CFTR (Cl- channel) 1/2000 whites |
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Neurofibromatosis
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cafe-au-lait spots
neurofibromas pheochromocytomas autosomal dominant signaling molec loss-of-fxn mutations |
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Duchenne's Muscular Dystrophy
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muscular weakness and degeneration
X-linked recessive dystrophin gene deletion Dx DNA test pseudohypertrophy of calf |
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Osteogenesis Imperfecta
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increased bone fx
blue sclera - translucent CT over choroid many mutations - abn collagen synth 1:10000 |
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Phenylketonuria
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autosomal recessive
phenylalanine hydroxylase deficiency tetrahydrobiopterin cofactor deficiency tyrosine becomes essential mental retardation fair skin (decreased melanin) eczema musty body odor decrease phenylalanine in diet increase tyrosine in diet |
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Fabry's disease
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X-linked recessive
alpha galactosidase deficiency ceramide trihexoside accumulation renal failure peripheral neuropathy hands/feet CV disease |
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Krabbe's disease
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Autosomal recessive
Bgalactosidase def galactocerebroside accumulation optic atrophy peripheral neuropathy/spasticity developmental delay |
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Gaucher's disease
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glucocerebrosidase def
glucocerebroside accumulation hepatosplenomegaly aseptic necrosis of femoral head bone crises Gaucher's cells (macrophages) |
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Niemann-Pick disease
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Autosomal recessive
sphingomyelinase def sphingomyelin accum in reticuloendothelial cells/parenchyma leading to organomegaly and progressive neurodegeneration cherry red spot on macula No Man PICKs his nose w/ a SPHINGer |
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Tay-Sachs disease
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Autosomal recessive
Absence of hexosaminidase A GM2 ganglioside accumulation Askenazi Jews (carriers = 1/30) death by age 3 cherry red spot on macula |
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Metachromatic Leukodystrophy
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Autosomal recessive
arylsulfatase A deficiency demyelination with w/ ataxia, dementia Cerebroside sulfate in brain, liver, kidney, PNS |
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Hurler's syndrome
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Autosomal recessive
alpha-L-iduronidase deficiency corneal clouding gargoylism developmental delay Hurlers (shot put) do more damage than hunters (arrows) |
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Hunter's syndrome
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X-linked recessive
iduronate sulfatase deficiency mild form of Hurler's (mild retardation) with aggressive behavior no corneal clouding |
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Lineweaver Burke plots
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noncompetitive inhibitors change the Vmax (the y-intercept will increase)
competitive inhibitors change the Km (the x-intercept will increase) |
what happens to plot with noncompetitive inhibitors? what about competitive ones?
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Sodium Potassium Pump
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BL membrane
moves 3 Na out, 2 K in, uses 1 ATP inhibitied by oubain, digoxin |
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Collagen synthesis and structure
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hydoxylation of proline/lysine residues in RER requires Vit C
procollagen exocytosed into ECM peptidases cleave terminal portion self-assembly into collagen fibrils crosslinked by lysyl oxydase |
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Ehlers-Danlos Syndrome
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faulty collagen synthesis causes:
hyperextensible skin tendency to bleed hypermobile joints |
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S-adenosyl methionine
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ATP + methionine = SAM
methyl group donor makes phosphocreatine regeneration with B12 |
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NAD+/NADPH
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NAD+ catabolic electron acceptor
NADPH anabolic electron donor product of HMP shunt makes superoxide regenerates GSH p450 |
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Glycolysis: irreversible reactions
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glu to G6P
G6P inhibits hexokinase F6P to F1,6BP ATP/citrate inhib PFK F2,6BP/AMP upreg PFK PEP to pyruvate ATP/Ala inhib Pyr Kinase F1,6BP upreg Pyr Kinase Pyr to AcetylCoA ATP/NADH/AcylCoA inhib Pyr DeH |
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Pyruvate Dehydrogenase Complex
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pyr + NAD+ + CoA ->
AcylCoA + CO2 +NADH 3 enzymes 5 cofactors: B1 thiamine B2 FAD B3 NAD B5 CoA lipoic acid |
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Pyruvate Dehydrogenase Deficiency
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buildup of pyruvate and alanine
reduced to lactate -> acidosis seen in alcoholics in B1 deficiency Rx: high fat/ketogenic nutrients |
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Cori cycle
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shuttles lactate from muscle to liver for regeneration to pyruvate
allows muscles to fxn anaerobically |
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TCA cycle
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12 ATP/Acyl CoA
24 ATP/glu molec 1st four enzymes are inhib by ATP/NADH Cindy Is Kind So She's Friendly More Often |
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Gluconeogenesis: irreversible reactions
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Pyr to oxaloacetate
Pyr carb req ATP/AcylCoA/biotin Oxaloacetate to PEP PEP carbK req GTP F1,6BP to F6P F1,6BPase G6P to glu G6Pase enzymes in liver, kidney, intestine hypogly with G6Pase def (von Gierke's) |
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Glucose 6 Phosphate Dehydrogenase Deficiency
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rate limiting enzyme of HMP shunt
necessary for RBCs to produce NADPH for GSH regeneration loss leads to hemolytic anemia triggered w/ oxidizing agents: sulfas, primaquine, fava beans Heinz bodies - Hb precipitates prevalent in Af-Am X-linked recessive |
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Fructose intolerance
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aldolase B deficiency
all phosphate accum in F1P inhib glycogenolysis/gluconeogenesis hypoglycemia, jaundice, cirrhosis Rx: decrease fructose/sucrose |
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Galactose intolerance
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galactose-1P uridyltransferase def
accum of toxic metabolites cataracts hepatosplenomegaly mental retardation Rx: decrease galactose/lactose |
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Essential Amino Acids
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PVT TIM HALL
phe val trp thr ile met his arg leu lys |
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Urea Cycle
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C from CO2 (mitochondria)
N from NH4 (mitochondria) N from aspartate (cytosol) |
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Phenylalanine derivatives
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Tyrosine, Dopa, DA, NE, Epi, Melanin, Thyroxine
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Tryptophan derivatives
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Niacin (NAD, NADP)
Serotonin Melatonin |
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Histidine derivatives
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Histamine
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Glycine derivatives
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Porphyrin/Heme
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Arginine derivatives
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Creatine
Urea Nitric Oxide |
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Homocytinuria
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defective cystathionine synthase or
defective methionine synthase cysteine become essential mental retardation osteoporosis lens subluxation tall stature kyphosis |
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Maple Syrup Urine Disease
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alpha ketoacid dehydrogenase def blocked degradation of branched aa (Ile, Leu, Val = I Love Vt maple syrup)
CNS defects, mental retardation, death |
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Adenosine Deaminase Definiciency
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SCID
Excess dATP prevents production of other deoxyribose nucleotides via ribonucleotide reductase -> lymphopenia |
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Lesch-Nyhan Syndrome
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X-linked recessive
LNS (Lacks Nucleotide Salvage) HGPRT deficiency -> dec IMP/GMP prod -> inc uric acid excr retardation self-mutilation aggression hyperuricemia, gout, choreoathetosis |
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Fatty Acid Metabolism
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Synthesis = cytosol
enters via citrate shuttle degradation = mitochondria enters via carnitine shuttle |
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von Gierke's disease
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Glycogen storage disease type I
glucose-6Pase deficiency (liver becomes like muscle) severe fasting hypoglycemia glycogen accum in liver Very |
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Pompe's disease
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Glycogen storage disease type II (trashes the pump)
lysomal alpha-1,4-glucosidase def cardiomegaly early death Poor |
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Cori's Disease
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Glycogen storage disease type III
deficiency of debranching enzyme alpha-1,6-glucosidase Carbohydrate |
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Glycogen storage disease type V
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McArdle's disease
muscle glycogen phosphorylase def glycogen in musc -> painful cramps, myoglobinuria w/ strenuous exercise Metabolism |
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Ketone bodies
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acetoacetate and betahydroxybutyrate
made in liver from HMG-CoA excr in urine (test for acetoacetate) elevated in starvation/DM ketoacidosis fruity breath converted to 2 AcetylCoA in brain |
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Insulin
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from pancreatic beta cells
inc glu uptake in musc/liver/fat GLUT2 R in beta cells GLUT4 in periphery inhib glucagon from alpha cells C-peptide cleaved -> activation |
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Glucagon vs. Insulin
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Glucagon phosphorylates
turns OFF glycogen synthase turns ON glycogen phosphorylase Insulin dephosphorylates turns ON glycagen synthase turns OFF glycagen phosphorylase |
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Cholesterol synthesis and esterification
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HMG-CoA reductase is the rate limiting enzyme in synthesis
inhib by Lovastatin Esterification via LCAT |
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Chylomicrons
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dietary TGs to peripheral tissues, dietary chol to liver
travel in lymphatics to thoracic duct to blood excess -> xanthomas Apo B48 mediates excretion Apo CII for lipoprotein lipase Apo E mediates liver uptake |
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VLDL
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hepatic TGs to periphery
excess causes pancreatitis apo B100 mediates secr apo CII for lipoportein lipase apo E mediates liver uptake |
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LDL
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produced via VLDL modification
hepatic cholesterol to periphery uptake via R-med endocytosis (Apo B100) excess causes ATH, xanthomas Bad for you |
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HDL
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periphery cholesterol to liver
repository for Apo C/E Apo A-1 for LCAT & chol-esters Good for you |
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Familial Hypercholesterolemia
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Increased Cholesterol/LDL
Auto Dom defect in LDL R xanthomas MI before 30y in homozygous pt |
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Familial Hypertriglyceridemia
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Increased TGs/VLDL
Hepatic overproduction of VLDL |
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Heme Synthesis
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Rate limiting step: glycine + succinyl CoA -> ALA via ALA synthase
occurs w/in mitochondria inhibition -> porphyrias Pb inhib other enzymes -> microcytic/hypochromic anemia and porphyria |
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Heme catabolism
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scavenged from RBCs
heme -> biliverdin -> bilirubin bilirubin excr in bile converted to urobilinogen excreted as urobilin in urine |
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Methemoglobinemia
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Fe in ferric (oxidized) state
low O2 affinity |
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Hb structure/affinity
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Cl, H, CO2, DPG, heat favor the T (taut) form over R (relaxed)
causes decreased O2 affinity |
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Vitamin A
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Retinol, in retinal pigment
deficiency: night blindness, dry skin |
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Vitamin B1
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Thiamine, cofactor in pyruvate carboxylase
deficiency: Beriberi and Wernicke's encephalopathy |
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Vitamin B2
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Riboflavin, FAD/FADH2
deficiency: corneal vascularization, cheilosis |
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Vitamin B3
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Niacin, NAD/NADH (from Trp)
deficiency: Pellagra caused by carcinoid syndrome, INH, Hartnup Dz Diarrhea, Dermatitis, Dememtia |
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Vitamin B5
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Pantothenate -> Coenzyme A
FA synth, Kreb's Cycle deficiency: Dermatitis, Enteritis, Alopecia, adrenal insufficiency |
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Vitamin B6
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Pyridoxine
Converted to Pyridoxal Phosphate cofactor in transamination (ALT/AST) |
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Biotin
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cofactor for carboxylation
1. pyruvate -> oxaloacetate 2. acetyl CoA -> malonyl CoA 3. proprionyl CoA -> methylmalonyl CoA |
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Folic Acid
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Coenzyme for 1-C transfer
methylation rxns for nitrogenous bases most common vitamin deficiency in US: macrocytic, megaloblastic anemia |
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Vitamin B12
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Cobalamin
Cofactor for homocyteine methylation & methylmalyonyl handling Stored in liver deficiency caused by: malabsorption (sprue, enteritis, diphyllobothrium latum), pernicious anemia, ileectomy Dx: Schilling test |
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Vitamin C
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Ascorbic Acid
cofactor for hydroxylation of proline/lysine in collagen facilitates Fe adsorption by keeping it reduced Deficiency: scurvy = swollen gums, bruising, poor healing |
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Vitamin D
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D2 absorbed from gut
D3 formed in skin 25OH D3 storage form 1,25OH D3 active form increases Ca/PO4 absorption deficiency: rickets, osteomalacia, hypoCa tetany excess: hyperCa, stupor, caused by sarcoidosis mphages producing active D3 |
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Vitamin E
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antioxidant protects RBCs against hemolysis
increased fragility of RBCs |
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Vitamin K
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synthesis of clotting factors II, VII, IX, X and Proteins C/S
synth'd by intestinal flora deficiency seen in broad-spectrum ABx, warfarin use inc PT, PTT, INR Neonatal hemorrhage |
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Ethanol Metabolism
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alcohol and acetaldehyde dehydrogenase produce NADH and acetate
excess NADH shunts pyruvate away from gluconeogenesis to lactate leads to hypoglycemia and FA synth (fatty liver) |
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Kwashiorkor vs. Marasmus
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Kwashiorkor - protein deficiency with skin lesions, edema, fatty liver
Marasmus - protein malnutrition with muscle wasting |
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