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101 Cards in this Set

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Chromatin Structure
negatively charged DNA wrapped around a histone (H2A, H2B, H3, H4), connected by H1.

Condensed = hetero-, inactive
Less condensed = eu-, active
histones
Nucleotides
Purines (A, G) large rings
Pyrimidines (C, U, T) small rings

PURe As Gold
CUT the PY (pie)
Eukaryotic DNA polymerases
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
DNA repair process
endonuclease cleaves strand upstream
exonuclease clease strand downstream
DNA polymerase Beta fills gap
3 steps
DNA repair defects lead to disease
Xeroderma Pigmentosum (UV light)
Ataxia-Telangiectasia (X-rays)
Bloom's syndrome (radiation)
Fanconi's anemia (crosslinking agents)
UV light
X-rays
Radiation
Crosslinking agents
Eukaryotic RNA polymerases
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...
Start and Stop Codons
Start
AUG (Are U Going?)
Stop
UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone)
1 Start, 3 Stop
Regulation of Gene Expression
Promoter - where RNA polymerase/transcription factors bind upstream
TATA (25 bp upstream)
CAAT (70 bp upstream)

Enchancer - where transcription factors bind to increase expression
RNA processing
1. 5' 7-methyl-guanine cap
stability, mediates translation
2. 3' Polyadenylation
stability, mediates nuclear export
3. Splicing out introns
for fun?
3 steps
tRNA Structure
75-90 nucleotides
anticodon end is opposite 3' aminoacyl
3' CCA sequence
chemically modified bases
tRNA charging
aminoacyl-tRNA synthetase
adds 1 aa to 3' end, using 1 ATP
proofreading capability
tRNA wobble
allows many codons to match one tRNA with only the first two bases of it's anticodon
PCR
ligate/denature DNA,
add premade specific probes
add heat-stable DNA polymerase
repeat until DNA sequence is amplified
Molecular Biology Techniques
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
ELISA
labeled Ab/Ag to Ag/Ab in pt sample
used in HIV
Sn = Sp = ~100%
Inheritance Modes
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
Variable expression
nature and severity of phenotype varies from one pt to another
Incomplete penetrance
Not all individuals with mutant genotype show dz phenotype
Pleiotropy
one gene has greater than one effect on phenotype
Imprinting
Differences in phenotype depend on whether the mutation is of maternal or paternal origin
Angelmans - maternal transmission
Prader-Willi - paternal transmission
Anticipation
Severity of disease worsens or age of onset decreases in successive generations
Loss of heterozygosity
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)
Dominant negative mutation
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
Linkage disequilibrium
two alleles at linked loci occur together more often than probability would suggest.
Hardy Weinberg population genetics
assumes no migration, no mutation, no natural selection, no mating preferences
Down Syndrome
mental and growth retardation
trisomy 21
tested with karyotyping
1:800
increased risk with maternal age
decreased AFP in amniotic fluid
polyhydramnios
Fragile X
mental retardation
characteristic facial features
large testes
X-linked
failure to express RNA binding protein
Sickle cell anemia
recurrent painful crises
autosplenectomy -> imm def
autosomal recessive
1 missense mutation in beta globin
1:400 Af-Am
Cystic fibrosis
recurrent pulmonary infections
exocrine pancreas insufficiency
infertility
autosomal recessive
mutated CFTR (Cl- channel)
1/2000 whites
Neurofibromatosis
cafe-au-lait spots
neurofibromas
pheochromocytomas
autosomal dominant
signaling molec loss-of-fxn mutations
Duchenne's Muscular Dystrophy
muscular weakness and degeneration
X-linked recessive
dystrophin gene deletion
Dx DNA test
pseudohypertrophy of calf
Osteogenesis Imperfecta
increased bone fx
blue sclera - translucent CT over choroid
many mutations - abn collagen synth
1:10000
Phenylketonuria
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
Fabry's disease
X-linked recessive
alpha galactosidase deficiency
ceramide trihexoside accumulation
renal failure
peripheral neuropathy hands/feet
CV disease
Krabbe's disease
Autosomal recessive
Bgalactosidase def
galactocerebroside accumulation
optic atrophy
peripheral neuropathy/spasticity
developmental delay
Gaucher's disease
glucocerebrosidase def
glucocerebroside accumulation
hepatosplenomegaly
aseptic necrosis of femoral head
bone crises
Gaucher's cells (macrophages)
Niemann-Pick disease
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
Tay-Sachs disease
Autosomal recessive
Absence of hexosaminidase A
GM2 ganglioside accumulation
Askenazi Jews (carriers = 1/30)
death by age 3
cherry red spot on macula
Metachromatic Leukodystrophy
Autosomal recessive
arylsulfatase A deficiency
demyelination with w/ ataxia, dementia
Cerebroside sulfate in brain, liver, kidney, PNS
Hurler's syndrome
Autosomal recessive
alpha-L-iduronidase deficiency
corneal clouding
gargoylism
developmental delay
Hurlers (shot put) do more damage than hunters (arrows)
Hunter's syndrome
X-linked recessive
iduronate sulfatase deficiency
mild form of Hurler's (mild retardation)
with aggressive behavior
no corneal clouding
Lineweaver Burke plots
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?
Sodium Potassium Pump
BL membrane
moves 3 Na out, 2 K in, uses 1 ATP
inhibitied by oubain, digoxin
Collagen synthesis and structure
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
Ehlers-Danlos Syndrome
faulty collagen synthesis causes:
hyperextensible skin
tendency to bleed
hypermobile joints
S-adenosyl methionine
ATP + methionine = SAM
methyl group donor
makes phosphocreatine
regeneration with B12
NAD+/NADPH
NAD+ catabolic electron acceptor
NADPH anabolic electron donor
product of HMP shunt
makes superoxide
regenerates GSH
p450
Glycolysis: irreversible reactions
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
Pyruvate Dehydrogenase Complex
pyr + NAD+ + CoA ->
AcylCoA + CO2 +NADH

3 enzymes
5 cofactors:
B1 thiamine
B2 FAD
B3 NAD
B5 CoA
lipoic acid
Pyruvate Dehydrogenase Deficiency
buildup of pyruvate and alanine
reduced to lactate -> acidosis
seen in alcoholics in B1 deficiency
Rx: high fat/ketogenic nutrients
Cori cycle
shuttles lactate from muscle to liver for regeneration to pyruvate
allows muscles to fxn anaerobically
TCA cycle
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
Gluconeogenesis: irreversible reactions
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)
Glucose 6 Phosphate Dehydrogenase Deficiency
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
Fructose intolerance
aldolase B deficiency
all phosphate accum in F1P
inhib glycogenolysis/gluconeogenesis
hypoglycemia, jaundice, cirrhosis
Rx: decrease fructose/sucrose
Galactose intolerance
galactose-1P uridyltransferase def
accum of toxic metabolites
cataracts
hepatosplenomegaly
mental retardation
Rx: decrease galactose/lactose
Essential Amino Acids
PVT TIM HALL
phe
val
trp
thr
ile
met
his
arg
leu
lys
Urea Cycle
C from CO2 (mitochondria)
N from NH4 (mitochondria)
N from aspartate (cytosol)
Phenylalanine derivatives
Tyrosine, Dopa, DA, NE, Epi, Melanin, Thyroxine
Tryptophan derivatives
Niacin (NAD, NADP)
Serotonin
Melatonin
Histidine derivatives
Histamine
Glycine derivatives
Porphyrin/Heme
Arginine derivatives
Creatine
Urea
Nitric Oxide
Homocytinuria
defective cystathionine synthase or
defective methionine synthase
cysteine become essential
mental retardation
osteoporosis
lens subluxation
tall stature
kyphosis
Maple Syrup Urine Disease
alpha ketoacid dehydrogenase def blocked degradation of branched aa (Ile, Leu, Val = I Love Vt maple syrup)
CNS defects, mental retardation, death
Adenosine Deaminase Definiciency
SCID
Excess dATP prevents production of other deoxyribose nucleotides via ribonucleotide reductase
-> lymphopenia
Lesch-Nyhan Syndrome
X-linked recessive
LNS (Lacks Nucleotide Salvage)
HGPRT deficiency -> dec IMP/GMP prod -> inc uric acid excr
retardation
self-mutilation
aggression
hyperuricemia, gout, choreoathetosis
Fatty Acid Metabolism
Synthesis = cytosol
enters via citrate shuttle
degradation = mitochondria
enters via carnitine shuttle
von Gierke's disease
Glycogen storage disease type I
glucose-6Pase deficiency
(liver becomes like muscle)
severe fasting hypoglycemia
glycogen accum in liver

Very
Pompe's disease
Glycogen storage disease type II (trashes the pump)
lysomal alpha-1,4-glucosidase def
cardiomegaly
early death

Poor
Cori's Disease
Glycogen storage disease type III
deficiency of debranching enzyme
alpha-1,6-glucosidase

Carbohydrate
Glycogen storage disease type V
McArdle's disease
muscle glycogen phosphorylase def
glycogen in musc -> painful cramps,
myoglobinuria w/ strenuous exercise

Metabolism
Ketone bodies
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
Insulin
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
Glucagon vs. Insulin
Glucagon phosphorylates
turns OFF glycogen synthase
turns ON glycogen phosphorylase
Insulin dephosphorylates
turns ON glycagen synthase
turns OFF glycagen phosphorylase
Cholesterol synthesis and esterification
HMG-CoA reductase is the rate limiting enzyme in synthesis
inhib by Lovastatin
Esterification via LCAT
Chylomicrons
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
VLDL
hepatic TGs to periphery
excess causes pancreatitis
apo B100 mediates secr
apo CII for lipoportein lipase
apo E mediates liver uptake
LDL
produced via VLDL modification
hepatic cholesterol to periphery
uptake via R-med endocytosis (Apo B100)
excess causes ATH, xanthomas
Bad for you
HDL
periphery cholesterol to liver
repository for Apo C/E
Apo A-1 for LCAT & chol-esters
Good for you
Familial Hypercholesterolemia
Increased Cholesterol/LDL
Auto Dom defect in LDL R
xanthomas
MI before 30y in homozygous pt
Familial Hypertriglyceridemia
Increased TGs/VLDL
Hepatic overproduction of VLDL
Heme Synthesis
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
Heme catabolism
scavenged from RBCs
heme -> biliverdin -> bilirubin
bilirubin excr in bile
converted to urobilinogen
excreted as urobilin in urine
Methemoglobinemia
Fe in ferric (oxidized) state
low O2 affinity
Hb structure/affinity
Cl, H, CO2, DPG, heat favor the T (taut) form over R (relaxed)
causes decreased O2 affinity
Vitamin A
Retinol, in retinal pigment
deficiency: night blindness, dry skin
Vitamin B1
Thiamine, cofactor in pyruvate carboxylase
deficiency: Beriberi and Wernicke's encephalopathy
Vitamin B2
Riboflavin, FAD/FADH2
deficiency: corneal vascularization, cheilosis
Vitamin B3
Niacin, NAD/NADH (from Trp)
deficiency: Pellagra
caused by carcinoid syndrome, INH, Hartnup Dz
Diarrhea, Dermatitis, Dememtia
Vitamin B5
Pantothenate -> Coenzyme A
FA synth, Kreb's Cycle
deficiency: Dermatitis, Enteritis, Alopecia, adrenal insufficiency
Vitamin B6
Pyridoxine
Converted to Pyridoxal Phosphate
cofactor in transamination (ALT/AST)
Biotin
cofactor for carboxylation
1. pyruvate -> oxaloacetate
2. acetyl CoA -> malonyl CoA
3. proprionyl CoA -> methylmalonyl CoA
Folic Acid
Coenzyme for 1-C transfer
methylation rxns for nitrogenous bases
most common vitamin deficiency in US: macrocytic, megaloblastic anemia
Vitamin B12
Cobalamin
Cofactor for homocyteine methylation & methylmalyonyl handling
Stored in liver
deficiency caused by: malabsorption (sprue, enteritis, diphyllobothrium latum), pernicious anemia, ileectomy
Dx: Schilling test
Vitamin C
Ascorbic Acid
cofactor for hydroxylation of proline/lysine in collagen
facilitates Fe adsorption by keeping it reduced
Deficiency: scurvy = swollen gums, bruising, poor healing
Vitamin D
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
Vitamin E
antioxidant protects RBCs against hemolysis
increased fragility of RBCs
Vitamin K
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
Ethanol Metabolism
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)
Kwashiorkor vs. Marasmus
Kwashiorkor - protein deficiency with skin lesions, edema, fatty liver
Marasmus - protein malnutrition with muscle wasting