Flashcards in Biochem Deck (194):
Fabry's dz =
XR; Lysosomal storage dz
No galactosidase A -> incr'd ceramide trihexoside
- periph neuropathy, angiokeratomas (skin problems), CV/renal dz
Gaucher's dz =
AR; most common lysosomal storage dz
No glucocerebrosidase -> incr'd glucocerebroside
- HSM!!!, aseptic necrosis of femur, bone crisis, Gaucher's cells (Mphage like tissue paper) [NO cherry red spot on macula!]
Niemann-Pick dz =
AR; Lysosomal storage dz
No sphingomyelinase -> incr's sphingomyelin
- progressive neurodegen, HSM!!!, CHERRY-RED SPOT on macula, foam cells, retard
AR; Lysosomal storage dz
No hexosaminidase A -> incr'd GM2 ganglioside
- progressive neurodegen, develop delay, CHERRY-RED SPOT on macula, lysosomes w/ onion skin, NO HSM; blindness, m. wkns; abnl startle reflex w/ sound stimuli; big head from accum in brain
Krabbe's dz =
AR; Lysosomal storage dz
No galactocerebrosidase -> incr'd galactocerebroside
- Periph neuropathy (no central!, develop delay, optic atrophy (blind), globoid cells
Metachromatic leukodystrophy =
AR; Lysosomal storage dz
No arylsulfatase A -> incr'd cerebroside sulfate
- Central/periph demyelination w/ ataxia, dementia
Hurler's synd (Scheie's is milder form) =
AR; Lysosomal storage dz
No a-L-iduronidase -> incr'd heparan sulfate and dermatan sulfate
- Develop delay, retard, gargoylism, airways obstruc (short neck), corneal clouding, HSM, CAD
Hunter's synd =
XR; Lysosomal storage dz
No iduronate sulfatase -> incr'd hepatan sulfate and dermatan sulfate
Mild Hurler's + aggressive behav, NO corneal clouding, retard
Carnitine defic =
Can't transport LCFAs into mito -> toxic accum
Wkns, hypotonia, hypoketotic hypoglc
- found in
- does what
death cap mushrooms (Amanita phalloides)
-> inhib's RNAPII, causes severe hepatotox if eaten
- affect on CYP?
Prok RNAP (only 1 in prok's)
Rev's up P450
How do euk's end trxn?
1) Rho-factor is RNA-dep ATPase to kick off RNAP
2) GC-rich region followed by U-rich region -> stem-loop/hairpin, kicks off RNAP
- what carries the AA?
- what NZ puts AA on tRNA?
- CCA on 3' end
- aminoacyl-tRNA synthetase; uses ATP (there's 1 NZ per AA)
- inhib what?
Bind 30S ribo subunit of prok's -> "aminoacyl-tRNA can't attach" and trsn can't occur
Euk ribo struc?
- what helps it assemble?
40S + 60S = 80S
- GTP hydrolysis -> initiation factors put it together w/ Met tRNA
tRNA uses ATP vs. GTP for?
ATP for act'n (charging) meaning putting AA on tRNA
GTP for gripping and going places (translocation) meaning connected to ribo and connecting new AA to growing AA chain
23S of 50S of prok ribo; catalyzes peptide bond formation using GTP
What do euk's/prok's need to translocate growing AA chain on ribosome?
Euk's - EF2
Prok's - EF G
Bind 30S prok ribo subunit and inhib formation of initiation complex -> "misreading of mRNA"
- works like?
Binds 50S ribo subunit and inhib's peptidyl transferase (aka ribozyme, 23S -> can't move growing AA chain from P to A site)
Macrolides (erythromycin, azithromycin, clarithromycin)
Bind 23S ribozyme of 50S ribo subunit and prevent release of uncharged tRNA after it has given it's AA
Works at 23S RNA in 50S subunit to prevent uncharged tRNA from leaving
Works at 50S ribo subunit to block translocation
Which drugs work at 30S and which at 50S?
Buy AT 30, CCELL at 50:
AT (30S) = aminoglycosides, tetracyclines
CCELL (50S) = Chloramphenicol, Clindamycin, Erythromycin (and other macrolides), Lincomycin, Linezolid)...also streptogramin
- clinical pic?
- MEAL: malnut'n, edema, anemia, liver (fatty change from decr'd apolipopr syn so can't get fat out), skin lesions too
- Small child w/ swollen belly
- complete calorie depravation
- m. wasting (Marasmus -> M. wasting), variable edema
Where does FA ox'n occur? What is this called?
Where does FA syn occur?
Where does steroid syn occur?
Where does choles syn occur?
- mito, b-ox'n
- SER (vs. RER for pr)
What metab'n occurs in both the mito and cytopl?
HUGs take 2:
Heme syn, Urea cycle, Gluconeogenesis
What NZ needs ATP? Needs biotin?
Kinase needs ATP to put phos on substrate
Carboxylase needs biotin to transfer CO2
Rate determining NZ of Glycolysis?
Stim'd by: AMP, F2,6BP
Inhib'd by: ATP, citrate
Rate determining NZ of Gluconeogenesis?
Stim'd by: ATP
Inhib'd by: AMP, F2,6BP
Rate determining NZ of TCA cycle??
Stim'd by: ADP
Inhib'd by: ATP, NADH
Rate determining NZ of Glycogen syn?
Stim'd by: glc, insulin
Inhib'd by: glucagon, EPI
Rate determining NZ of Glycogenolysis?
Stim'd by: AMP, EPI, glucagon
Inhib'd by: insulin, ATP
Rate determining NZ of HMP shunt?
Stim'd by: NADP+
Inhib'd by: NADPH
Rate determining NZ of de novo pyrimidine syn?
Carbamoyl phosphate synthetase II
Rate determining NZ of de novo purine syn?
Inhib'd by: AMP, IMP, GMP
Rate determining NZ of Urea cycle?
Carbamoyl phosphate synthetase I
Stim'd by: N-acetylglutamate
Rate determining NZ of FA syn?
Acetyl-CoA carboxylase (ACC)
Stim'd by: insulin, citrate
Inhib'd by: glucagon, palmitoyl-CoA
Rate determining NZ of FA ox'n?
Carnitine acyltransferase I
Inhib'd by: malonyl-CoA (bc need more FAs)
Rate determining NZ of Ketogenesis?
Rate determining NZ of Choles syn?
Stim'd by: insulin, thyroxine
Inhib'd by: glucagon, choles
CoNZ A carries?
4 uses of NADPH?
anabolic processes, resp burst, P450, glutathione reductase (antiox't)
Where is GLUT 1-4? Which req's insulin to work?
1 - in neurons and RBCs
2 - in liver and b-cells of panc
3 - all cells (NOT brain)
4 - SkM and adipose (INSULIN dep)
- Histones have lots of? Charge?
Histones H2A/B, H3 and H4, each 2x, w/ DNA wrapped 2x around them -> H1 btwn each nucleosome
- Lys and Arg -> (+) charge
Deamination of ? to ?
? only in RNA, ? only in DNA
Cytosine to Uracil
Uracil -> Thymidine
AAs for purine syn?
Make pyrimidines from?
Gly, Aspartate, Glutamine
Gly, THF, CO2
Carbamoyl phosphate + Aspartate
Diff btwn nucleosides and nucleotides?
-Sides have base + ribose (sugar)
-Tides have base + ribose + phosphaTe (3'5' phosphodiester bond)
Purines = ?
How to make them?
AMP + GMP (AG)
Ribose 5-P (sugar) + PRPP (phosphate) -> add base -> IMP -> AMP or GMP
Pyrimidines = ?
How to make them?
TMP/UMP and CTP
Temp base (orotic acid) from carbamoyl phosphate via CPS II (*RL*)
-> add (sugar + phosphate) = UMP
-> UDP -> CTP or...
dUMP via ribont reductase -> dTMP via thymidylate synthase (THF co-factor)
CPS I and II -> differences?
CPS I - in mito, urea cycle, N from ammonia (MAKES carb phos to enter into urea cycle)
CPS II - in cytosol, pyrimidine syn, N from glutamine (used carb phos to make orotic acid to make pyrimidines)
Ornithine transcarbamoylase defic =
No OTC in urea cycle -> accum of carbamoyl phospahte -> made into orotic acid via CPSII in cyto (pyr pthwy) -> excreted in urine; neuro problems from high ammonia levels
inhibs ribont reductase; no UDP to dUDP in pyrimidine syn pthwy
(used in SCA to make more HbF
blocks PPRP amidotransferase NZ in purine de novo syn pthwy
blocks thymidylate synthase; no dUMP to dTMP so low dTMP (pyrimidine syn pthwy)
inhib's euk dihydrofolate reductase, so decr'd THF and decr'd dTMP in pyrimidine syn pthwy
inhib's bac dihydrofolate reductase, so decr'd THF and decr'd dTMP in pyrimidine syn pthwy
Can get orotic aciduria from what 2 defects?
How to tell them apart?
Defect in UMP synthase (pyrimidine syn pthwy) OR ornithine transcarbamylase defic (in urea cycle)
- No hyperNH3 in UMP syn defect; high NH3 in urea cycle defect
IMP can form?
GMP or AMP (purine salvage)
or can be degraded to inosine, to hypoxanthine, to xanthine (via xanthine oxidase) -> uric acid (via xanthine oxidase again)
ADA defic =
Can't break down Adenosine -> Inosine in purine salvage pthwy -> high ATP and dATP -> inhib of ribont reductase -> no new DNA syn -> decr'd lymph's -> SCID, AR
- recurrent infec's, D, failure to thrive
Lesch-Nyhan synd =
XR - no HGPRT, so no purine salvage (no guanine to GMP and no hypoxanthine to IMP) -> lots of uric acid prod and de novo purine syn
- retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
Guanylic acid =
Inosinic acid =
Adenylic acid =
GMP, IMP, AMP
If co-ad'd w/ 2 drugs -> higher tox's of them, which 2 drugs?
Blocks xanthine oxidase, so no uric acid produced -> for gout
- 6-MP and azathioprine bc they too are metab'd by xanthine oxidase
Permanent cells types
Neurons, SkM, cardiac m., RBCs
Nissl bodies =
RER in neurons, makes NZs (ChAT which makes ACh) and peptide nt's
Diff btwn RER and free ribo's?
Cells rich in RER/SER?
RER makes secretory pr's and N-linked oligosaccharide onto pr's
Free ribo's make cytopl and organelle pr's
SER makes steroids and does detox
RER: goblet cells (secrete mucus), pl cells (secrete Abs)
SER: liver (detox), ad cortex (steroid syn)
Golgi adds ? onto AAs?
Modifies N-oligosaccharide on Asparagine
Adds O-oligosaccharide on Ser and Thr
Adds M6P on pr's (-> lysosomes)
I cell dz sx?
Coarse facial features, clouded corneas, restricted jt movement, high pl levels of lysosomal NZs
COPI vesicular trafficking pr does?
Backwards: Golgi->Golgi, Golgi->ER
Forwards: GolgiGolgi or ER to Golgi
catab of LCFAs and AAs
barrel-shaped pr complex that degrades ubiquitin tagged pr's
Direc of dynein vs. kinesin?
Helical array of polymerized dimers of a/b-tubulin, ea dimer has 2 GTP bound
Dynein moves retrograde to microtubule
Kinesin moves anterograde to microtubule
Chediak-Higasi synd =
- 3 sx?
mutation in LYST (lysosomal trafficking) -> no microtubule-dep sorting of endosomal pr's
- recurrent pyogenic infec's, partial albinism, periph neuropathy
CIlia made of?
Kartagener's synd is defect in?
9+2 microtubules, w/ dynein arms btwn 9 microtubule doublet's around outer edge -> bends cila
- no dynein arm
-> male infertil, decr'd female fertil, bronchiectasis, recurrent sinusitis; assoc'd w/ situs inversus
These stains for intermediate filaments are for which cell type?
inhibits Na/K pump by binding K site
Type I =
1: strong type (bone, skin, tendon, late would repair) (defec in osteogenesis imperfecta -> bad matrix)
2: slippery type (carTWOlage, vitreous body)
3: bloody type (reticulin - skin, bl vessels, uterus, fetal tissue, granulation tissue) (defec in EDS w/ X-linking EC'ly)
4: bm or basement lamina (defec in Alport synd)
Collage syn steps
1) Syn in RER (Gly-X-Y) of a-chains (preprocollagen)
2) ER: Hydroxylation of Pro and Lys (VitC)
3) ER: Glycosylation of Lys-OH in pro-a-collagen and form procollagen w/ H and di-S bonds -> 3x helix of procollagen
4) exocytosis of procollagen
5) EC: cleave di-S rich term region -> insol tropocollagen
6) X-link staggered tropocollagen (Lys to Lys-OH) (need Cu lysyl oxidase) -> collagen fibrils
Prader-Willi synd =
chr 15, Paternal allele not expressed (loss from pat chr, and mom's in inact'd)
- mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
AngelMan's synd =
chr 15, Maternal allele is lost (not exp'd) and allele from dad is inact'd
- mental retardation, seizures, wide-based gait (ataxia), inappropriate laughter
Hypophosphatemic rickets =
XD (all daughters of affected fathers affected)
incr'd phos wasting at PT -> rickets-like presentation
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu synd) =
AD, d/o of bl vessels
- telangiectasia, recurrent epistaxis, skin discolorations, AV malformations
Hereditary spherocytosis =
AD defect in spectrin or ankyrin
- hemolytic anemia, incr'd MCHC
NF type 1 =
cafe-au-lait spots, neural tumors, Lisch nodules (iris hamartomas), sk d/o's, optic gliomas
NF type 2 =
AD, chr22 of NF2 gene
bilat acoustic schwannomas, kid cataracts
Tuberous sclerosis =
AD, defect in tuberin gene (tumor suppressor?)
facial lesions (adenoma sebaceum, like pimples), hypopig'd ash leaf spots on skin, cortical/retinal hamartomas, seizures, mental retard, renal cysts/angiomyolipomas, cardiac rhabdomyomas, incr'd incidence of astrocytomas
von Hippel-Lindau dz =
AD, deletion of VHL (tumor suppressor) gene on chr3 -> act'n of HIF (TF) and act'n of angiogenic GFs
hemangioblastomas of retina/Ce/medulla, bilat RCC + other tumors (pheos)
N-acetylcysteine to loosen mucus plugs bc cleaves di-S bonds in mucus gp's
Be Wise Fool's GOLD Heed's Silly HOpe
DMD (and Becker's)
Ornithine transcarbamoylase defic
Fragile X synd =
X-linked CCG repeat affected FMR1 gene (Fragile mental retard.)
- lg testes, long face, lg jaw, lg everted ears, autism, retarded
4 tri-nt repeat d/o's?
Fragile X CCG
Friedreich's ataxia GAA
Myotonic dystrophy CTG
Preg quad screen for:
- Down synd? U/S shows?
- Edwards synd?
- Patau's synd?
- decr'd aFP, incr'd bHCG, decr'd estriol, incr'd inhibin A; incr'd nuchal translucency (also in XO)
- decr'd aFP, decr'd bHCG, decr'd estriol, nl inhibin A
- decr'd free bHCG, decr'd PAPP-A, incr'd nuchal translucency
Diff btwn Edwards and Patau's synd?
Trisomy 18 vs. 13
Both: severe mental retard, rocker-bottem ft, VSD
Edwards: sm jaw, low-set ears, prominent occiput, clenched hands
Patau: sm head/eye, cleft lip/palate, ONE EYE, polydactyly, holoprosencephaly
Robertsonian translocations occurs in which chr's?
13, 14, 15, 21, 22
Cri-du-chat synd =
deletion of short arm of chr5
- crying/mewing, sm head, retarded, epicanthal folds, VSD
Williams synd =
microdeletion of long arm of chr7, inc'ing elastin gene
- Like Will Ferrel from Elf = elfin facies, stupid, verbal skills, friendly, hyperCa (so excited to see the sun when he can!) bc very sensitive to VitD
22q11 deletions -> ?
2 assoc'd synds?
bad 3/4th pouches: cleft palate, abnl facies, thymic aplasia (T cell defic), cardiac defects, hypoCa 2* to no PT gl
- DiGeorge synd (thymus, PT and heart defects) and Velocardiofacial synd (palate, heart, face defects)
3 ways to get Pyr DH defic?
Means that you can't go into TCA cycle from Glycolysis -> lactic acidosis, cell swelling and apoptosis
1) Congenital X-linked gene for E1-a subunit of PDC -> neuro deficits, trtmt: eat ketogenic foods to make Acetyl-CoA from ketones (Lys and Leu are purely ketogenic)
2) Alcoholics w/ thiamine defic (co-factor)
3) Arsenic inhib's lipoic acid (co-factor) -> V, rice water stools and garlic breath
ETC inhib's at:
- Complex I
- Complex III
- Complex IV
- other one that causes Parkinson's like sx?
I = Rotenone, barbiturates
III = Antimycin A
IV = CN, CO, H2S, N3 (azide)
MPP -> Parkinson's like sx
ATP synthase (Complex V) inhib?
Uncoupling agents (3)?
Oligomycin (ETC stops working)
2,4DNP (wood preservative), ASA, thermogenin in brown fat (ETC continues working but ATP syn stops)
What do RBCs use to protect themselves from FRs?
Reduced GSH is made by glutathione reductase from GSSG, using NADPH from HMG shunt (2GSH from 1 NADPH); GSH is an imp IC antiox't
G6P defic =
- what precipitates an attack?
- benefit of defect?
- on histo see what 2 things in RBCs?
XR; No HMP shunt, so can't make as much NADPH -> hemolytic anemia bc RBCs don't have defense against ox'ing agents
- usu infec -> hemolysis
- incr'd malarial resistance
- Heinz bodies (ox'd precipitated Hb) and Bite cells (after Mphage bite out Heinz bodies)
What is the equivalent of catalase in RBCs?
Glutathione peroxoidase (H2O2 to water)
Essential fructosuria =
how is fructose used?
AR; no fructokinase
- benign, asymp, fruc in bl/urine (some diuresis)
- hexokinase can make F6P from fruc -> used in pthwys
Fructose intol =
- what happens in cells?
AR, no aldolase B
- F1P accum's -> low phos and inhib of glycogenolysis and gluconeogenesis
- hypoGlc, liver problems (jaundice, cirrhosis), V, decr'd Phos (all on Fruc)
- don't eat fructose or sucrose
Galactokinase defic =
- what happens in cells?
AR; no galactokinase
- galactitol accum's in cells
- galac in bl/urine, baby cataracts (don't track object, no social smile -> eye problems!)
Classic galactosemia =
- what happens in cells?
AR; no galactose-1-phosphate uridyltransferase
- accum of toxic sub's in cells (inc: galactitol)
- failure to thrive, liver problems, baby cataracts, retard, hypoGlc
- don't eat galactose or lactose
Pneumonic to remember fruc vs. galac d/o's of metab?
Fruc is to aldolase B as galactose is to uridyl transferase
Cells w/ only aldose reductase -> ?
Make sorbitol from glc but can't make fruc from sorbital (no sorbitol DH NZ)
- Schwann cells, retina, kidneys
Essential AAs =
- which is semi-essential?
PVT TIM HALL
Phe, Val, Thr
Trp, Ile, Met
His, Arg, Leu, Lys
Which AAs are:
- Met, Val, His
- Phe, Ile, Thr, Trp (PITT)
- Lys, Leu
- Asp, Glu (- at body pH)
- Arg < Lys, His (no charge) (+ at body pH) (Arg and Lys in histones bc bind - DNA)
How is ammonium transported in the body (from m. to liver)?
- if you have too much NH4+, what happens?
M: from AAs it's put onto a-KG to make glutamate -> transfered to Pyr (left over enters Cori cycle to make lactate) to make Alanine -> goes thr bl (Alanine cycle) -> liver: makes glutamate again -> urea cycle
- a-KG is depleted -> no TCA cycle and no E
How to trt hyperNH4+?
Limit pr in diet
Benzoate or phenylbutyrate -> bind AA -> excreted
Lactulose (bac eat it and lower pH) to acidify GI -> trap NH4+ -> excreted
Ornithine transcarbamoylase defic =
XR; urea cycle d/o (NZ to make citrulline)
Excess carbamoyl phos -> orotic acid -> out in bl/urine; decr'd BUN, sx of hyperNH4+
PKU (phenylketonuria) =
AR; no phenylalanine hydroxlase or no THB=BH4 cofactor -> can't make Tyr from Phe -> incr'd Phe -> phenylketones (phenyl-acetate, lactate, pyr)
- retard, sm head, sm growth, seizures, fair skin (no melanin), eczema, musty (mousy) body odor (bc incr'd aromatic molec's)
- decr'd Phe and incr'd Tyr intake
Malignant PKU =
No DHB reductase -> no BH4 -> can't metab Tyr nor Phe, also can't make 5HT from Trp
- decr'd syn of nt's -> neuro problems even w/ good diet tx
- not Phe, give L-DOPA and 5HT
AR; no homogentisic acid oxidase -> can't brk down Tyr to Fumarate (incr'd homogentisic acid)
- benign, dark ct, brown sclera, urine turns blk when left out, arthralgias (toxic to cart)
3 ways to get homocysteinuria and their trtmts:
- which AA becomes essential?
- looks like?
1) cystathionine synthase defic (Rx: less Met, more Cys and B12 in diet)
2) decr'd aff of above NZ for B6 co-factor (Rx: more B6 in diet)
3) no homocysteine methyltransferase NZ (Rx: req's B12 and folate)
- homocysteine in urine, retard, osteoporosis, tall, kyphosis, lens sublux (down/in), atherosclerosis (stroke, MI), damages vessel walls -> thormbosis
- Marfans habitus
AR; no COLA transporter in kidney (cysteine, ornithine, lysine, arg) so no reab'n
- cystine in urine -> hexag crystals and staghorn calculi (usu in kids)
- acetazolamide to alkalinize urine -> no stones made
Maple syrup urine dz =
AR; no a-ketoacid DH (B1) -> no brkdwn of branched AAs (Ile, Leu, Val = I Love Vermont)
- Ile/Leu/Val in bl, CNS defects, retard, feeding problems, seizures
Hartnup dz =
AR; no neutral AA transporter in kidney/GI
- Trp in urine and decr'd ab'n in gut -> pellagra bc no B3 (niacin)
- more pr in diet
How do glucagon/EPI work to incr glc?
How does insulin incr glycogen?
AC -> cAMP -> PKA phos's glycogen phosphorylase kinase -> active NZ can phos glycogen phosphorylase -> brks down glycogen
R TK dimerizes -> phos's pr phosphatase to inact glycogen phosphorylase and to inact glycogen phorphorylase kinase -> less glycogenolysis
Glycogen is degraded by?
Glycogen phosphorylase (brks a1,4 links) (in SkM) (makes G1P)
Debranching NZ (brks a1,6 links) (makes glc)
- Some in lysosomes by a1,4-glucosidase (makes glc + Pi)
4 glycogen storage dz's?
Very Poor Carb Metab:
I: Von Gierke's - no G6phosphatase
II: Pompe's - no lysosomal a1,4-glucosidase
III: Cori's - no debranching NZ
V: McArdle's - no SkM glycogen phosphorylase
VonGierke's dz =
AR; glycogen storage dz, no G6Pase
- can't make glc -> hypoGlc, incr'd glycogen in liver/kidneys (big liver/kidneys, hepatosteatosis), incr'd bl lactate, hyperlipidemia, hyperuricemia
(only in liver and renal tub cells bc no NZ in muscle)
Pompe's dz =
- in adult-type see?
AR; glycogen storage dz; no lysosomal a1,4-glucosidase (aka acid maltase)
- Pompe's trashes heart, liver, m.; cardiomegaly, retard, hypotonia, macroglossia
- diaphragm wkns and resp failure
Cori's dz =
AR; glycogen storage dz; no debranching NZ
- mild vonGierke's, can brk down some glycogen, nl bl lactate levels, see dextrin-like struc's in cyto of hep's
McArdle's dz =
AR; glycogen storage dz; no SkM glycogen phosphorylase
- incr'd glycogen in M's that can't be broken down -> cramping, myoglobinuria and lactic acidosis w/ exercise
Why does body make ketone bodies?
When TCA cycle is stalled: starvation -> oxaloacetate gone for gluconeogenesis; w/ EtOH excess NADH shunts oxalo to malate
-> glc and FFA produce ketone bodies via HMG-CoA synthase -> brain and m. use them by making 2 AcCoA -> TCA cycle
Apolipopr's - on who? does what?
E: all except LDL, Extra remnant uptake
A-I: HDL, act's LCAT (esterify choles)
C-II: chylo/VLDL/HDL, LPL cofactor
B-48: chylo, chylo secretion into bl
B-100: VLDL/IDL/LDL, binds LDL R
AR; no MTP (microsomal TG transfer pr) gene -> no B-48 or B-100 -> decr'd chylo/VLDL syn/secretion
- lipid in enterocytes of GI; failure to thrive, steatorrhea, acanthocytosis (burr cells), ataxia, night blindness
- VitE helps
inhib's EtOH DH, antidote for methanol or ethylene glycol poisoning
Disulfiram (Antabuse) =
inhib's acetaldehyde DH -> high acetaldehyde, hangover sx (V, flushing)
How does EtOH -> hypoglc?
- Since no TCA ->?
It's metab'n -> incr'd NADH/NAD+ ratio in liver -> pyr to lactate and OAA to malate -> no gluconeog. -> stim's FA synthesis -> hypoGlc and hepatic fatty change
- Acetyl-CoA is made into ketones; OAA to malate which is broken down to give more NADH
What are the signs of hypoCa?
Chvostek's sign (Cheek) - tap CN VII on cheek -> facial spasm
Trousseau's sign (Tighter cuff) - tighten BP cuff on arm -> arm spasm
- high levels of?
no homogentisic oxidase to brk down homogentisate (from Tyr) to maleylacetoacetate (goes to TCA)
- homogentisic acid
- blk urine on ox'n, blk cart, degen arthritis
2 mito DNA d/o's?
Leber's hereditary optic neuropathy, myoclonic epilepsy
W/ EtOH abuse, what is:
- NADH level
- metab acid/alkalosis? due to what 2 ions?
- why get gout?
- why get high TGs?
- why get fasting hypoGlc?
- high (pyr -> lactate)
- acidosis bc lactic acid and b-hydroxybutyric ketoacidosis from aceteoacetate
- other acids complete w/ uric acid for renal excretion, so have high levels of it
- high NADH so make NAD+ by DHAP -> Glycerol-3-P, which makes TG in liver
- oxaloacetate depletion from gluconeogenesis and no substrates for TCA, so low glc
- AST > ALT, high GGT
MPTP drug, made by by-product of syn of meperidine, can cause?
Irreversible Parkinson's dz; cytotoxic to neurons in nigrostriatal DA pthwy
Sx of ASA overdose:
First resp alk (stim'n of resp center) -> metab acidosis w/ incr'd anion gap
- salicylates damage inner mito mem -> E released as heat -> hyperthermia
- hemorrhagic gastritis, fulminant hepatitis
Why is estrogen pro-coag?
Decr's syn of ATIII and incr's syn of factors I (fibrinogen), V and VIII
- use what stat analysis, why?
- what is dz is rare?
OR, bc we determine how many people are w/ and w/o dz, but if dz is rare then OR = RR
What study do you use to determine:
- dz incidence
- dz prev
- longitudinal cohort study
- X-sectional study
SD / SqRt[n]
Type I vs. II error =
Power of a study =
false(+) vs. false (-)
Power = 1-b, where b is prob of Type II error [=probability of rejecting a Ho when it really is false]
3 ways to incr the power of a study?
Incr sample size (power in #s), incr expected effect size, or incr precision of measurement
How to calc CI?
- what should the CI not include for there to be a significant diff btwn 2 variables? what about if it's the CI for OR or RR?
CI = range from mean +/- Z(SEM)
Where Z for 95% CI is 1.96, and for 99% CI is 2.58
- don't include zero!
- don't include one!
What does the test measure:
- X2 test
- r2 coefficient
- diff btwn means of 2 groups (binary)
- diff btwn means of 3+ gps (cont vs. cat)
- diff btwn 2+ categorical (%) outcomes (cat vs. cat)
- coeff of correlation btwn 2 cont variables
Disease prevention: 1*, 2*, 3* =
- prevent, detect (early), and reduce disability
Apgar score =
- scores are based on?
- good/bad scores are?
10 pt scale of newborn assessed at 1 and 5 mins
- Appearance, Pulse, Grimace, Activity, Resp
- >7 good, 4-6 assist/stimulate, <4 resuscitate
Low birth wt =
- hold head up
- sits, crawls, X-midline
- stranger anxiety
- climbs stairs
- kicks ball
- parallel play
- rides tricycle,
- group play
- stacks how many blocks at 1 and 2yrs
- hold head up: birth-3mo (social smile)
- sits, crawls, X-midline: 7-9mo
- stranger anxiety: 12mo
- walks: 12mo
- climbs stairs: 12-24mo
- kicks ball: 24-36mo
- parallel play: 24-36mo (also: pee at three)
- rides tricycle: 3yr (copies drawings, complete sentences)
- group play: 4yr (dresses self, hops on 1 foot, simple drawings)
- age x3 -> 3 blocks at 1yo, 6 at 2yo
- calc'd by?
- underwt? nl? overwt? obese? morbidly obese?
wt in kg / (ht in m)2
- 30 obese, >40 morbid obesity
EEG waveforms in sleep:
- awake, drowsy, N1, N2, N3, REM?
"BATS Drink Blood"
awake: Beta (high freq, low amp)
N1 light sleep: Theta (sm, rounded)
N2 grinding teeth: Sleep spindles (pushed together) and K complexes (high amp)
N3 deepest non-REM, no memory: Delta (low freq, high amp) (opp of awake!)
- super active so high amp: sleepwalk, night terrors, bedwetting
REM, no memory: Beta (like awake!)
REM sleep has activity from where?
- nt during REM?
PPRF (paramedian pontine reticular formation/conjugate gaze center) -> extraocular eye movements
- ACh, NE reduces during REM
What changes in sleep in depressed people?
Incr'd REM (comes on faster) and early-morning awakenings
When it get darks out, what stim's you that it's time for bed?
Dark -> SCN of hypo -> NE release -> pineal gl releases melatonin -> sleep
Where is glucokinase?
- induced by?
In liver and b cells of panc, aka cells that reg glc
Baby w/ neuro sx, lactic acidosis, seizures, retarded, ataxia and spasticity =
Pyr DH defic
(back up of Pyr->lactic acid, low E in cells bc no enter into TCA from glycolysis)
Where does gluconeogenesis occur?
Where can it not occur?
In the liver, NZs also in kidney and GI epi
Muscle bc no G6Pase
Heinz bodies + bite cells = ?
- see ox'd Hgb in RBCs from oxidative stress that can't be reduced bc no NADPH
- see bite cells bc Mphage bit out Heinz bodies
Phe is used to make?
- cofactors needed?
Tyr (->T4) -> Dopa (w/ Cu ->Melanin) -> DA -> NE -> EPI
- BH4 to make Tyr and Dopa (hydroxylase NZ)
- B6 to make DA
- VitC to make NE
- SAM to make EPI
Tryptophan is used to make?
- cofactors needed?
w/ B6 to Niacin
w/ NH4 to 5HT -> melatonin
Histidine is used to make?
w/ B6 to Histamine
Glycine is used to make?
w/ B6 to porphyrin -> RL by ALA synthase to Heme
Arg is used to make?
Creatine, Urea, NO
Glutamate is used to make?
w/ B6 to GABA
BH4 is used to make what neurotransmitters?
Tyr (from Phe), Dopa (from Tyr)
5HT from Trp
B6 is used to make what neurotransmitters?
DA (from Dopa)
Niacin (from Trp)
Histamine (from Histidine)
Porphyrin (from Glycine)
GABA (from Glutamate)
Albinism due to congenital defect in what 2 possible things? Or lack of migration of?
1) no Tyrosinase, so don't make melanin from Tyr
2) defective Tyr transporters so decr'd Tyr and thus decr'd melanin
3) lack of migration of neural crest cells
FA syn occurs where?
- end product?
In cyto, get citrate out of mito via citrate shuttle
- AcCoA w/ B7(CO2)-> MalonylCoA -> Palmitate -> FA syn
FA degradation occurs where?
- end product?
In mito, get FA into mito bc combining it w/ CoA to make Acyl-CoA, which bring into mito via carnitine shuttle
- AcylCoA -> b-ox'n to AcetylCoA which can become ketones or go into TCA cycle
What are ketone bodies?
What are they used for?
RL NZ for their syn?
Made from FAs and AAs when TCA cycle is shut down (no OAA, no NAD+)
- Brain uses ketones bc metab's them to 2 molec's of AcCoA -> enters TCA cycle and makes E
- HMG-CoA synthase
How many cal's is 1 gm pr/carb/fat?
4 kcal for pr/carb
9 kcal for fat
Mutation in xeroderma pigmentosum?
Mutation in HNPCC?
Mutation in ataxia-telangiectasia?
nt excision repair (endonuclease)
mismatch repair NZ
repair of double-stranded breaks
Night blindness, dry skin, xerophthalmia (dry cornea), silver/gray plaques on conjunctiva, keratomalacia (clouding of cornea), sq metaplasia =
- in excess will see?
Dry eyes can ulcerate -> go blind
- skin changes, HA, incr'd ICP, pseudotumor cerebri, papilledema
- active as?
- used for what rxns?
- TPP (thiamine pyrophosphate)
- Pyr DH and aKG DH rxns, also transketolase in HMP shunt (and in branched chain AA DH)
Vasodil, edema and cardiomegaly in undernourished child, due to?
Wet ber1ber1 (B1) - high output HF, edema
- Dry is polyneuritis, symm m. wasting
Cheilosis and corneal vascularization =
B2 defic (riboflavin)
No B6 -> defic in what other vitamin?
B3 (niacin) bc need B6 to make B3 from Tryptophan
Dermatitis, enteritis, alopecia, ad insuff =
B5 (pantothenate) defic [CoA and FA syn]
- active form?
- used as cofactor for?
- used to make?
- pyridoxal phosphate
- transamination (ALT/AST), decarboxylation rxns, glycogen phosphorylase
- Cystathionine (Cysteine), Heme, Niacin, Hist, nt's (5HT, EPI/NE, GABA)
Convulsions, irritability, periph neuropathy and sideroblastic anemia =
- deficiency can be induced by (3)?
B6 defic (no GABA -> convulsions, no heme -> sideroblastic anemia)
- EtOH, INH, OCPs
- cofactor for?
- deficiency can occur w/? (2)
- carboxylation NZs (Pyr carboxyl to OAA, AcCoA carboxyl to malonylCoA, propionyl-CoA carboxyl to methylmalonylCoA, aka step 1 of brkdwn of OCFAs)
- Abx, avidin in egg whites
- active form?
- used as cofactor for?
- 1C transfer/methylation rxns
- cofactor for what 2 NZs?
- homocysteine methyltransferase (make Met from Homocys) and methylmalonyl-CoA mutase (methylmalonylCoA to succinylCoA in OCFA brkdn to enter TCA)
Can get buildup of homocysteine from defic's in what 2 vitamins?
1) no B12, can't make Met, have high cysteine and high methylmalonylCoA
2) no B6, can't make Cysteine, have high Met and can't make Hgb either so have sideroblastic anemia)
Met + ATP =
- regen of it is dep on?
- need it to make?
- B12 and folate
- EPI from NE
VitC is needed for what 3 things?
1) keeping Fe2+ in reduced state and THF in reduced (active) state
2) Hydroxylation of Pro and Lys in collagen syn
3) Conversion of DA -> NE
Periph neuropathy, ataxia PLUS hemolytic anemia =
VitE defic bc it's an antiox't and protects RBCs and mem's from FR damage, w/o it -> hemolysis, m. wkns, post column and spinoCe tract demyelination, LDL ox'n