biochem fun
Terms
undefined, object
copy deck
- eukaryotic genome has ____ origin(s) of replication
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multiple
replication begins at consensus sequence of AT base pairs - xeroderma pigmentosum
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defective excision repair (especially of thymine dimers)
AR inheritance - RNA polymerases (eukaryotes)
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RNA pol I: rRNA
II: mRNA
III: tRNA
*a-amantin inhibits RNA pol II
RNA pol has no proofreading fxn, but can initiate chains.
RNA pol II opens DNA at promotor regions - start codon
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AUG
=methionine in eukaryotes
=f-met in prokaryotes - stop codons
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UGA
UAA
UAG - splicing of mRNA
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introns sliced out of primary mRNA transcripts
lariat shaped intermediate
snRNPs facilitate splicing by binding to mRNA and forming spliceosomes - RNA processing
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occurs in ucleus in eukaryotes
1: capping on 5' end
2: polyadenylation on 3'
3: splicing out of introns
(before all this happens, the initial transcript is referred to as hnRNA) - tRNA structure
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antiocodon end is opposite from 3' [aminoacyl] end
all have CCA at the 3' end, where the amino acid is bound - two factors responsible for accuracy of amino acid selection
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aminoacyl tRNA synthetase
binding of charged tRNA to the proper codon
**a mischarged tRNA reads the usual codon but inserts the wrong amino acid - energy sources for translation
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ATP: tRNA charging (via aminoacyl tRNA synthetase)
GTP: tRNA translocation - RER
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site of EXCRETED protein synthesis
goblet cells of small intestine and plasma cells are rich in RER (secrete mucus and antibodies, respectively) - nissl bodies
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in neurons: RER
synthesize enzymes (like ChAT) and peptide neurotransmitters - SER
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stie of steroid synthesis and detoxification of drugs/poisons
hepatocytes and adrenal cortical cells have lots of SER - I cell disease
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failure of addition of M-6-P to lysosomal proteins (so can't be targeted to lysosome)
are instead excreted
Sx: coarse facial features and restricted joint movement - drugs that act on microtubules
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mebendazole
taxol (anti-breast CA)
griseofulvin
vincristine/vinblastine
colchicine - chediak higashi syndrome
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due to a microtubule polymerization defect
results in decreased phagocytosis - Kartagener's syndrome
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due to dynein [ATPase that causes bending of cilia] arm defect
results in immotile cilia
(dyein = retrograde
vs kinesin = anterograde) - Gq receptor
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HAV and M 1, and M 3
act thru phospholipase C
IP3 = increased [Ca]i
DAG = protein kinase C activity - Gs receptor
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B1, B2, D1, H2, V2
acts thru adenylyl cyclase
increased cAMP = protein kinase A activity - Gi receptor
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M2, A2, D2
INHIBITS adenylyl cyclase - collagen types
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Be Cool, Read Books
type I: bones (90% of collagen)
II: cartilage
III: reticulin (skin, vessels, uterus, fetal tissue)
IV: basement membrane
X: epiphyseal plate -
collagen synthesis
(inside fibroblasts) -
1: alpha chains translated on RER
2: in ER: hydroxylation of proline and lysine [need vit C]
3: golgi: glycosylation of pro-alpha-chain, fomraiton of procollagen (triple helix)
4: procollagen molecules exocytosed into extracellular space -
collagen synthesis
(outside fibroblasts) -
5: procollagen peptidases cleave terminal regions (tropocollagen formed)
6: tropocollagen moelcules are reinforced by cross-linkage to make collagen fibrils - Ehlers Danlos syndrome
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faulty collagen synthesis
->hyperextensible skin
->easy bruising
->hypermobile joints
*associated with berry aneurysms - osteogenesis imperfecta
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AD inheritance
abnormal collagen synthesis
->multiple fractures (can occur during birth process)
->blue sclerae
->hearing loss (abnormal middle ear bones)
-> dental imperfections
*type II is fatal in utero
*often confused w/child abuse - glucokinase
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found primarily in the liver
lower affinity (higher Km) but higher capacity (higher Vmax)
only HEXOkinase is feedback inhibited by G-6-P - irreversible enzymes of glycolysis
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hexokinase/glucokinase (glucose to G-6-P)
PFK-1 [rate limiting]
pyruvate kinase (PEP to pyruvvate)
pyruvate dehydrogenase (pyruvate to acetyl CoA) - PDH complex
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3 enzymes that require 4 cofactors:
-> B1 (thiamine): pyrophosphate
-> B2 (riboflavin): FAD
-> B3 (niacin): NAD
-> B5 (pantothenate): CoA
-> lipoic acid
*PDH is activated by:
NAD + : NAD ratio
high ADP
high Ca - PDH deficiency
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backup of substrates (pyruvate and alanine)
results in lactic acidosis
*seen in alcoholics due to thiamine [B1] deficiency
Tx: high intake of ketogenic nutrients (fat, lysine, leucine) - cori cycle
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transfers excess reducing equivalents (lactate, pyruvate) from RBCs/muscle to liver
allows muscle to fxn anaerobically (net 2 ATPs) - TCA cycle
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3 NADH, 1 FADH2, 2 CO2, 1 GTP
= 12 ATP per acetyl CoA
= 24 total ATP per glucose
Can I Keep Selling Sex For Money, Officer? - irreversible enzymes of gluconeogenesis
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Pathway Produces Fresh Glucose
pyruvate carboxylase
PEP carboxykinase
fructose 1-6 bisphosphatase
glucose-6 phosphatase
**muscle canNOT participate in gluconeogenesis (only liver, kidney, GI epithelium)
**hypoglocemia caused by deficiency in these enzymes - HMP shunt
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produces ribose-5-phosphate from G-6-P for nucleotide synthesis
NADPH from NADP+ for fatty acid and steroid biosynthesis
*occurs in cytoplasm of mammary glands, liver, adrenal cortex
*no ATP produced - G6PD deficiency
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rate limiting enzyme in HMP shunt
low NADPH in RBCs = unable to keep glutathione reduced (so can't detox)
leads to HEMOLYTIC ANEMIA
*XLR inheritance - fructose intolerance
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AR deficiency of aldolase B
fructose-1-phosphate accumulates
* low available phosphate left for gluconeo and glycogenolysis
==>hypoglycemia, jaundice, cirrhosis, vomiting
Tx: reduce intake of fructose and sucrose [glucose + fructose] - essential fructosuria
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defect in fructokinase
BENIGN, ASYMPTOMATIC
frucose appears in blood and urine
(earlier enzyme in fructose metabolism pathway) - galactosemia
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no galactose-1-P uridyltransferase
AR inheritance
accumlation of toxic substances
Sx: cataracts, hepatosplenomegaly, MR
Tx: exclude galactose and lactose (glucose + galactose) - galactokinase deficiency
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galactosemia and -uria
can also lead to toxic accumulation [of galactitol] if too much galactose in diet - essential amino acids
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ketogenic: leu, lys
gluco and keto: ile, phe, trp
gluco: met, thr, val, arg, his
PriVaTe TIM HALL - acidic and basic amino acids
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acidic: aspartate, glutamate
[- charge at pH 7.4]
basic: arginine, lysine
[+ charge at pH 7.4]
neutral: histidine (at 7.4)
**arg and lys found in high amounts in histones that bind to (-) DNA - urea cycle
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Ordinarily, Careless Crappers Are Also Frivolous About Urination
ornithine, carbomyl phosphate, citrulline, aspartate, arginosuccinate, fuberate, arginine, urea
*in liver. carbamoyl phos step occurs in mt (rest in cytosol) - amino acid derivatives
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phe: tyrosine, DA, NE, Epi, thyroxine, melanin
trp: niacin, 5HT, melatonin
his: histamine
glycine: porphyrin-> heme
arg: creatine, urea, NO
glutamte: GABA - phenyketonuria
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deficiency of either
->phenylalanine hydroxylase ,or
-> THB cofactor
tyrosine becomes essential
Sx: MR, growth retardation, fair skin, eczema, musty body odor
Tx: low phe, high tyr in diet
AR inheritance - alkaptonuria
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deficiency of homogentisic acid oxidase (in tyrosine deg path)
aklapton bodies -> black urine when standing
also have dark connective tissue
benign disease! - albinism
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deficiency of
->tyrosinase (no melanin)
->tyrosine transporters
may be from a lack of migration of neural crest cells (like Hirschprung disease) - homocystinuria
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cysteine becomes essential
Sx: MR, osteoporosis, tall stature, kyphosis. lens probs, and atherosclerosis - cystinuria
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inherited defect of renal tubular aa transporter for COLA
->cystine, ornithine, lysine, arginie
Tx: acetazolamide to alkalinize the urine - MSUD
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blocked degredation of branched aa's (ile, leu, val)
Sx: severe CNS defects, MR, death - adenosine deaminase deficiency
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a cause of SCID
excess ATP and dATP imbalances the nucleotide pool
->feedback inhibition of ribonucleotide reductase
low lymph count (B and T) - Lesch-Nyhan syndrome
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absence of HBPRTase
->converts hypoxanthine to IMP
and guanine to GMP
XLR inheritance
Sx: MR, self-mutilation, aggression, hyperuricemia - these organs' cells don't need insulin for glucose uptake
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BRICK L
Brain, RBCs, Intestine, Cornea, Kidney, Liver -
GLUT2 found in ____
GLUT4 found in ____ -
B cells of pancreas
muscle and fat - von Gierke's disease
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type I glycogen storage disease
G-6-P deficiency
severe fasting hypoglycemia, high glycogen in liver, hepatomegaly, high blood lactate - Pompe's disease
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type II glycogen storage disease
lysosomal a-1,4 glucosidase
cardiomegaly and systemic findings
leads to early death - Cori's disease
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type III glycogen storage
deficiency of debranching eyzme a-1,6 glucosidase
milder form of von Gierke's
normal blood lactate levels - McArdle's disease
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type V glycogen storage
skeletal muscle glycogen phosphorylase
high glycogen in muscle, but can't break it down
painful cramps + myoglobinuria with exercise - mneumonic for glycogen storage diseases
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Very Poor Carbohydrate Metabolism
von Gierke's, Pompe's, Cori's, McArdle's - Fabry's disease
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XLR inheritance
def: a-galactosidease A
accum: ceramide trihexoside
peripheral neuropathy of hands and feet
angiokeratomas
cardio/renal disease - Gaucher's disease
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def: B-glucocerebrosidase
accum: glucocerebroside
hepatospleno, aseptic necrosis of femur
bone crisis, Gaucher's cells [macs] - Niemann-Pick disease
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def: sphingomyelinase
accum: sphingomyelin
progressive neurodegeneration
hepatospleno
cherry-red spot on macula - Tay-Sach's disease
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def: hexosaminidase A
accum: GM2 ganglioside
progressive neurodegeneration
developmental delay
cherry red spot, onion skin lysozymes - Krabbe's disease
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def: B-galactosidase
accum: galactocerebroside
peripheral neruopathy
developmental delay
optic atrophy - metachromatic leukodystrophy
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def: arylsulfatase A
accum: cerebroside sulfate
central and periphreal demyelination
ataxia, dementia - Hurler's syndrome
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def: a-L-iduronidase
accum: heparan/dermatan sulfate
developmental delay
gargoylism, airway obstruction, corneal clouding, hepatospleno - Hunter's syndrome
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*XLR*
def: iduronate sulfatase
accum: heparan/dermatan sulfate
mild hurlers + aggressive behavior
NO corneal clouding - fatty acid metabolism sites
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synthesis: citrate shuttle carries acetyl CoA to cytosol
oxidation: carnitine shuttle carries acyl-CoA to mt matrix - major apolipoproteins
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A-1: activates LCAT
->catalyzes choesterol esterification (forms new HDL)
B-48: secretion of chylomicrons
B-100: binds to LDL receptor
C-II: cofactor for LPL
E: chylomicron remnant uptake by liver - familial dyslipidemias
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I: hyper-chylomicronemia
IIa: hypercholesterol (low LDLR)
IIb: high LDL, VLDL
III: dysbeta (IDL, VLDL)
IV: VLDL, TG
V: mixed (VLDL, chylos) - acute intermittent porphyria
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defciency in uroporphyrinogen I synthetase
porphobilinogen, delta-ALA accumulate in urine - prophyria cutanea tarda
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def: uroporphyrinogen decarboxylase
uroporphyrin accumulates in urine (tea colored)
photosensitivity also - symptoms of porphyrias
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5 Ps
Painful abdomen
Pink urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs - Vitamin A
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[retinol]
deficiency: night blindness, dry skin, impaired immune response
excess: arthralgias, fatigue, headaches, skin changes, sore throat, alopecia - vitamin B1
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[thiamine]
deficiency: Beriberi and Wernicke-Korsakoff syndrome
=cofactor for oxidative decarboxylation of a-keto acids [pyruvate, a-ketoglut)
dry beriberi: polyneuritis + muscle wasting
wet: high output cardiac failure (dilated cardiomyopathy), edema - vitamin B2
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[riboflavin]
deficiency: angular stomatitis, corneal vasc, cheliosis
FAD and FMN are derived from riboflavin! - vitamin B3
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[niacin]
deficiency: PELLAGRA.
->diarrhea, dermatitis, dementia, beefy glossitis
NAD derived from niacin - vitamin B5
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[pantothenate]
deficiency: dermatitis, enteritis, alopecia, adrenal insuff
is a constituent of CoA - vitamin B6
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[pyridoxine]
def: confusions, hyper- irritability, periph neuropathy
*is converted to pyridoxal phosphate (AST ALT, decarboxylation, heme synthesis) - vitamin B12
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[cobalamin]
cofactor for homocysteine methylation
stored in liver
only synthesized by bacteria - biotin
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defic: dermatitis, enteritis [ingestion of raw eggs, antibiotic use]
*is a cofactor for carboxylation rxns - vit C
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scurvy: swollen gums, bruising, anemia, poor wound healing
necessary in collagen synthesis
facilitates iron absorption
necessary as cofactor for DA->NE - vit E
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defic = increased RBC fragility
is an antioxidant that protects RBCs from hemolysis - zinc deficiency
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delayed wound healing, hypogonadism, low adult axillary/facial/pubic hair
can predispose to alcoholic cirrhosis - ethanol metabolism
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NAD+ is the limiting reagent
alcohol dehydrogenase operates via zero-order kinetics
*disulfiram: inhibits acetaldehyde dehydrogenase (2nd step) - malnutritions
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Kwashiokor: protein [edema, anemia, fatty liver]
Marasmus: protein-calorie [tissue wasting] - ethanol hypoglycemia
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high NADH/NAD+ ratio (due to ethanol metabolism using NAD+)
causes diversion of pyruvate to lactate/ OAA to malate
inhibits gluconeogenesis-->hypoglycemia