Usmle Medical Biochemistry

8/13/2019 Usmle Medical Biochemistry

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MEDICAL BIOCHEMISTRYUSMLE step 1Last moment revision

www.gims-org.com

Also included harmone related topics


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Terms Definitions

Glucosid sugar 4th -OH to other's -O- or -S-

3 G-genoses with \\fasting G liver P-rylase, liver debrancher, vonGierke,

blood glucose norm

range

70-90mg/dL from 1)diet 2)fasting Cori Cycle for

gluconeogenesis from Lactate 3)Glutamine of muscle wasting

extra AcAc path

TCA:extra AcAc+SuccinylCoA+thioXase=AcAcCoA; +HMG-

synthase=HMG; +reductase=mevalonic:Chol-ol vs TCA:extra

citric:AcAc:Malonic:FA

Glycerin mild

oxidation=

Glycerol+H2O2=DHA(aceton OH,=O,OH)+GA(aldehyge

OH,OH,=O)

G1P pathGal-to-G: Gal+Gal-kinase=Gal1P; +GalT+UDP-G=G1P;

+Gmutase=G6P:G6pase=G

HFI vs DFI vs EFI

Hered-ry Fructose Intoler(aldolaseB def://F1P) * Dietary FI (F

malabsorp-n) enterocyte FK def:bloat,diarrh,constip-n vs Hepat

FK=Clinitest

aldolase A vs B def-

cy

A:G-neogenes(GA3P+DHAP=F1,6-biP):severe hypoglycaemia;

vs B:F+Fkinase=F6P,+aldB=DHAP+GA(GA+3ose kinase=..)

prolonged DKA

/ketoacids: \pH: kaussmaul="Produvka" to \\CO2 to

/pH),vomit,abdom pain,flu,confus-n: lethargy:obtund-n/dull

alert/conscious),brain edema:coma

fat(=3-glycerids)

lipolysis

glycerid+3FA: further 3keton bodies: aceton, acetoacetate,b-

OH-butirate (mistake:b-OH-butirate not keton{R-(C=O)-R}):1o

muscle fuel,2/3brain

starvation 1o fuel

brain-2/3 ketons,1/3 G, muscle-FA,including branched, RBC-G,

immune cells & kidney-Glutamate

Gluconeogenesisin fasting: as muscle wasting:1o fuel, but not in starving: saved

for RBC only!

lipolysisboth fasting (some for muscle) & starving(marked:1o for

muscles as keton bodies)

brain fuel @ starv-n 3 ketobodies

Gluconeogenesis

enzymes PC-PEPC-F1,6biPase(rate lim)-G6Pase(vonGierke)


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fruity vs musty

breath vs malodor

urine

keto=aceton breath(ketotic state) vs PKU(def PA-OH-ase:\\Y) vs

\\homogentis-xidase:Alkaptonuria:dark on air urine/red wax/blue

ears

//E:small branched

G-gen debrancher deficiency

4C & 5C linear

diCarboxylic, if

+NH2=?

4C=succinic (+NH2=D,+more NH2=N); 5C=glutaric

(+NH2=E,+more NH2=Q); D-NH2(liver deamin-n)=OA; E-

NH2=a-ketoacid (vs b-keto in FA)

Apo100 & 48 from Apo100 from liver, 48 from intestine

liver & ketones for

fuel

Liver canNOT use AcAc as cardiac:

SuccinylCoA+AcAc+AcAcCoA(thio)X-ase=AcAcCoA; +HMG-

synthase=HMG; +lyase=AcAc

why folate \\ in

alcoholics

folate (B9) loss in urine/stool (bear offset loss providing extra

folate!)

P-lat-n by Insulin vs

Glucagon

fed:Insulin deP-lates(activates)P-ase:G6P loose P:bond to

glycogen chain:fasting:Glucagon P-lates(activates)P-kinase

NADPH source &

targetfrom PPP for reducing stressed RBC

most "-

"&"+"(basic)AA

Glutamine:"-"=acidic:travel farthest in e-phoresis;most"+"=basic:Arginine remain at anode("-"pole giving "-

"electrons)

ketobodies sourceadipose:hormon-sens lipase:TG:FA; mito:FA b-oxid-

n:AcCoA:AcAcCoA

\G,/k; \\\G,/k; \\G,\k;

/diCOO+\\G,\k

hepat GlycogenP-rylase; G6P-tase(Glycogen store d-se); FA b-

oxid-n block; FAcylCoADH=AR (aut/reces) MCAD in homozig

N.Europe kid

MCAD

fasting:FA:AcylCoA:carntin shuttle:b-oxid:keto(save G for

brain);N.Europe aut-rec homozig kid can't utilize own

fat:G


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fasting overnight vs

2d

Glycogenolys:Gluconeogenesis vs

Proteolys:lactate:G6P:G:FA:keto

Glucose norm level

vs SIDS

norm fasting G=4.2-6.1 (64 - 128 mg/dL) vs 20%MCAD(white

kid):SIDS: 250)

energy for protein

synthGTP

energy for cardiac

muscleFA b-oxid-n to ketone bodies

galactose to G=G-

neogenes

lactose+lactase=G+Gal;+galactokinase+Gal1P;+GALT+UDP-

G=UDP-Gal+G1P;+PG-mutase=G6P;+G6P-ase=G

Galactosemia

AR: GALT def: excess Gal-to-galactitol (polyol=sugar

alcohol):act as sorbitol:// plasma osmos:damaged

lens,CNS,liver

Gal1P excess toxic: retard,cirrhosis,ren damage,

Gal-kinase defbenign AR:+"urine Clinitest"(detect all reducing sugars=all but

"G+F" sucrose)

benign & toxic //Gal

vs //F

Gal//: benign:\GalK: /urine Gal:Clinitest,

tox:GALT(retard,cirrhos,renal); vs F//:benign:Essential(\hepaticFK), tox:Heredit(\AldB):cirrhos

reducing sugars all monosugars with free aldo- (not cyclic), NOT sucrose (G+F)

F metab-msucrose+sucrase=G+F; +F-kinase=F1P; +aldolaseB=GA(then

needs trioseKinase)+DHAP

F can be synth from mannose:-ol:DH:F or sorbitol:DH:F

F essential for sperm in seminal vesicles

Essential F-uriaAR: hepatic fructokinase def-cy(+Clinitest),less severe than

hereditary fructose intolerance

hered-ry F

intolerance

AR:aldolaseBdef(split F1P=DHAP+GA):\\G & accumul F1P(toxic

to liver:cirrhosis); \\C3 interm-tes:\\G-neo: fasting hypoG-emia

hered-ry F intoler-ce

& cell P

excess F traps P:cell \\P:\\ATP:RBC hemolysis, //AMP(accum-

n)://purines://uric:gout; Rx:table sugar(sucrose)-free diet

seminal tubules:G-

Sorbitol-F G +aldose reductase=Sorbitol; +sorbitol DH(DeHydrogenase)=F


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tissues w/aldose

reductaselens, retina, Schwann, ova & seminal vesicles, kidney

DM:///G:///Sorbitol://

osmos:?

lens:cataract; retina:microaneurism&pericytes

destructionSchwann:perif neuropathy

Gaucher vs Guerke[gosh'ei]: \\cerebrosidase:cerebrosid accumul-n (brain OK) vs

\\G6Pase:no Gluconeogenesis from hepat.glycogen

McArdle20yo:cant utilize muscle glycogen(liver can):on exercise:muscl

cramps+hematuria

fasting fuelGlutamine(immun,kidney,guts),G(RBC),1/3G+2/3ketone(brain),

FA(muscles)

DKA=after 24hstarvation

unRx DM(often 1st time DS): hyperglycemia but

starvation+stress(infection)=hyperketos+acidos:denatur, fruity

smell=nail polish remover

DKA

\\\insulin(unRx DM mostly Type1)+//stress hormons(infect-

n):///ketobodies:pH\\:severe acidos(6.9-7.1),under

6.7=permanent denatur:death

DKA symp

xx tired,aceton breath,/// thirst+const urin-n,muscle waste:

///weight-loss,oral/genital thrush(bact on xx

glucose),aggress,agit-n,irrit-n

Glucose uptake

mechanism

b-cell:insulin:6min in blood: tyrosin-receptors: GLUT-4

synthes:takes glucose from blood; after 6min \\\insulin: \\Glut-

4:no Gluc uptake

glucagon role

unRx DM Type1:beta-cell \\insulin: in 6 min

\\insulin://glucagon:mostly act on

hepatocyte:glycogenolysis:keep sugar in blood for RBC

if b-cell inhibitedin 6min blood insulin\\:no Tyr signal:\\newGLUT4 synth &

old\\:\\G uptake:sugar stays in blood & //:starv-n:ketobodies:\\pH

norm pH,severe

acidosis,death

norm7.35-7.45; :DKA:severe acidos 6.9-7.1 rapidly in 24h;

under 6.7:death (permanent denatur-n of blood proteins)

insulin-independent

cellsnot usual GLUT-4, but GLUT-?:brain,liver,b-cells,intestine

urine sugar///gluc:tubule SGLT overused:spill to urine:take water:water loss

(=Diabetes):dehydration:thurst

Mannitol,Mannite,M sorbitol isomer:osmotic diuretic,weak renal vasodil-r,sugaralcohol(polyol)~sorbitol but lose H+in sol-n=acidic:needs bicarb


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anna Sugar to norm pH

MannitolIV \\ acutely raised intracranial P:fiter,no reabs:pulls H2O in

urine:\\POsm:ECF:ICF:\\brain cell edema; >20g=kids laxative

Mannose-G-Gal vsF

3 aldoses(=O on 1stC):Man:2d, G:3d, Gal:4th -OH on L-side(up); vs F=ketose (=O on 2d)

# of G for Palmitic

syntheachG gives 2AcetylCoA x4G=16C

ATP # from Palmitic

oxid-n

C16={8AcetylCoA(each=2CO2&2H2O=12ATP)=96ATP; addit-ly

7NADHx3ATP+7FADH2x2ATP=35ATP}=131

aldoses Hexoses 1stC=O: (2d=ketose F) G:3d -OH left-up; Mannose:2,3; Gal:3.4

aldolase B def Hered Fructose Intolerance (aldolase B +fructose-1P=glyceraldehyde+dihydroacetone)

galactokinase def galactosemia

gl6P

dehydrogenase def

\PPP(=HMS-hexose-mono shunt): \\NADPH synth: no

Glutathionine restored: // radicals: \RBC defense: if Oxid stress:

hemolitic anemia

ALT:AST=1:2 alcoholic "alphabetic" hepat

Hepatic d-ers

Alcohol(ALT:AST=1:2, toxic=Fatty Liver); Drug-induced:

fever,rush,arthralg,/eosinophil; WD:\\cerulloplasmin+Kayser-

Fleischer ring; HepB

muscle branch-

chain AA-DH \\

degrades NOT in liver but muscle only, by "Branched-chain AA-

DH-ase", if deficit: Maple syrup in urine

G6P-ase \\

vonGierke:aut.recess:accum glycogen:\\G,1yo ///

Uric,lactic,TG,Ch-ol,keto(from FA),liver damage:fail:bleed

diates, liver adenoma

HGPRTv \\ //uric:gout,retard,selfmutil-n:Lesch-Hyhan (1 of 10 X-link)

GALT \\accum Gal://galactitol(//osmos:damaged lense,CNS):Heredit

Galactosemia

f-OH-ase \\ accum fenylKetone,\\Y:PKU

homogentisic acid

oxidase \\

not oxidized homogentisic=toxic tyrosine byproduct:harmful to

bone/cartilage,urine black:Alcaptonuria(=ochronosis)

fumarylAcAc AR://Y:cabbage odor,cirhosis to hepatocellular carcinoma:


7/27

hydrolase \\ hereditory Y-osis

hepatic F-kinase \\ mild Essential F-uria

Aldolase B \\//F takes all P:\\ATP:weak RBC:hemolysis,//AMP:gout:hered-ry

F intolerance

Ascites in

alcoholosm//hydrostat P in Splanchnic capillares

yellow greesy

enlarged liver

#1alcoholism:steatosis=fatty liver

(less:CCl4,DM,obesity,malnutrition):lipid accumul in hepatocyte

displacing nucleus

lysosomal storage

d-es

AR:accum GAG, sphingolipids,G-gen(Pompei d-se); 2

exceptions:not AR but X-linked:Fabry & Hunter

lysosomal storage

d-es

mistake@Golgi post-translational modif-n of enzyme:no

Mannose P-lation:no receptor bond/pinch/vesicle X-port/fuse

w/lyzosome

statins

iHMG-CoA reductase(rate-limiting step in cholesterol

synth:AcAcCoA:Mevalonic:Cholesterol):sole major cholesterol-

lowering drugs

statins vs Nystatinmajor cholesterol-lowering drugs=iHMG-CoA reductase(rate-

limiting step in cholesterol synth) vs antiFungal

HMG-CoA

reductase

3-hydroxy-3-methyl-glutaryl-CoA reductase,8-transmembrane

domain anchored in membrane of ER (endoplasmic reticulum)

HMG-CoA lyase Cholesterol-HMG-AcAc-23ATP

Hyperlipoproteinemi

as

1:chylo, 2:LDL, 3:dis-b("remnant d-se"), 4:VLDL, 5=1+4

(chylo+VLDL)

CH & fasting

fasting do not effect Cholesterol (all in HDL); norm CH97% of blood Chol-ol(


8/27


9/27

newspaper(=fibrillary) in macrophage,//serum acid P-ase from

macrophage

KrabbeGalactosyl-ceramidase:abnorm myelin:retard,CNS

histiocytes(multinucleated globoid)

Fabry

def a-GalactosidaseA:accum ceramid-3-hexoside, X-linked

recessive inherited lysosomal storage:skin

angiokeratomas,HT,ren fail

von Gierke

AR: liver&kidney G-neogenesis: G6P-ase def:accum

G6P:accum G-gen:1yo://uric:tubule\\\excret uric(gout) &

lactic(acidosis)

von Gierke load testgive F,Gal or Glucagon: NO blood G// (missing G6P-

ase:1yo://uric)

Pompea-1,4G-idase=acid maltase=only G-genosis lyzosomal storage

d-se: accum G-gen in lyzosomes in many tissues:

Pompe & heart G-gen depo in heart:restrictive cardiomyopathy

myeloma///blood protein synthesis:depo protein fibrills in heart(restrictive

cardiomyopathy:\\CO) & kidney(fail)

Tay-Sachs(NO

hepatosplen)

AR:4-nucleotide insert-n:frame shift in

hexoAminidaseA://GM2=Sph-lipidos;norm birth:6mo:blind,cherrymacula,retard,lamellar lyzosom

Tay-Sachs

hexoAminidaseA \\ :Sph-lipidos:accum GM2 in

ganglion=gangliside:swallen retina ganglions="macular Cherry

Spot"

Tay-Sachs sympt macular change,seizure,spasticity,mental retard-n

gangliosidosis

Tay-Sachs:hexoAminidaseA \\ :Sph-lipidos:accum GM2 in

ganglion=gangliside:swallen retina ganglions="macular Cherry

Spot"

mutation: 3 types

point mutation(silent,missense,nonsense),

frameshift:insrtion/delition not 3 nucleotides(insert4 in

hexoaminidase=Tay-Sachs); AA lost(as F in CF)

laminated mito vs

lamellar lyzosome

Hurler:mucopolysaccharidosis:heparan & dermatan sulfate &

Sunfilippo:heparan s vs GM2 ganglioside in Tay-Sach

lipid storage

disordersGaucher's [gosh'ei],Niemann-Pick


10/27

Gaucher [gosh'ei] glucocerebrosid accum in RE cells & CNS

Newmann-Pick sphingomyelin

Lesch-

Nyhan:boy\\HGPRT

1of10X-link: gout mom:norm birth,late sit,most never walk,//uric

acid:gout,stone(allopurinol!),retard,~palsy,~Huntington,selfmutil-n

Foam cell Nieman-Pick

P-Lipids(Glycerol+2FA+P=Phosphatidic

Acid)+Serin,Inositol,Ethanolamin,Cholin(Lecithin)

Sphingolipid parts (Serin+2FA+P=Ceramid)+Cholin(Sphingomyelin)

yellowish tendon

depo

Greek: yellow=xanthoma=xanthomata=xanthomatosis):yellowish

cholesterol-rich depo in tendons

FHFamilial hypercholesterolemia 2:genet dis-r: //LDL, //"bad

cholesterol"

FH reasons1)mut LDLR gene encoding protein(LDL rec-r (removes LDL

from the circul-n); 2)apolipoprotein B (ApoB)

Xanthoma+Xanthe

mia+corneal arc

def LDL r-tor (recognizor of B100 of VLDL synthesized in liver)

in Clathrin pit: \\endocytos of Cholesterol: cholesterol accum

outside of cells

allopurinoliXO (Xanthine oxidase): reversible non-comp-ve inhib of

XO+purin=hypoxanthin, +more XO=uric

physostigmine iCholinestherase:AcetylCholin// (reversible non-comp-ve inhib)

organophosphates iCholinestherase:AcetylCholin// (irreversible inhib)

VLDL &

chylomicron main

part

TG, Xport as lipoproteins (with apo100 & 48 by lymph)

LDL estim-nFreidewald: LDL(2.4-4)=Tot Chl(3-5.2 or


11/27

excess Hemosiderin

(Fe-store)

heart fail:pulm capillary:macrophage Hemos-n laden("heart

failure cell")

Xlink boy purple

nodules all skin

Fabry:a-galactosidase A\\:biopsy:cavernous hemangioma

w/epidermal keratosis:too thick vessel wall:AMI,HT,ren fail

38yo heredit

ointpain,blue ears

ochronosis=alkaptonuria(block PA-to-Tyr: // homogentisic

acid:degenerative arthropathy 40th, X-ray:lumbar disc degener-

n & Ca+-n

Heme synthesis in

RBC

Gly+SuccinylCoA(ALA-synthase)=sigma-ALA; +Porphobilinogen

synthase=P-gen; +Ferrochelatase=Heme

HFI vs DFI vs EFI

Hered-ry Fructose Intoler(aldolaseB def://F1P) * Dietary FI (F

malabsorp-n) enterocyte FK def:bloat,diarrh,constip-n vs Hepat

FK=Clinitest

aldolase A vs B def-

cy

aldolaseA: G-neogenes (GA3P+DHAP=F1,6-biP): severe

hypoglycaemia; vs B in F+Fkinase=F6P, +aldB =DHAP+GA

(then GA+3ose kinase..)

prolonged DKA

kaussmaul="Produvka" to \\CO2:return pH),vomit,xx abdom

pain,flu,confus-n:lethargy:obtund-n(dulled alert/conscious-

s),diab.coma,brain edema

fat(=3-glycerids)lipolysis

glycerid+3FA:further 3keton bodies:aceton,acetoacetate,b-OH-

butirate(mistake:b-OH-butirate not keton{R-(C=O)-R}):1omuscle

fuel,2/3brain

starvation 1o fuelbrain-2/3 ketons,1/3 G, muscle-FA,including branched, RBC-G,

immune cells & kidney-Glutamate

Gluconeogenesisin fasting: as muscle wasting:1o fuel, but not in starving: saved

for RBC only!

FA synth rate lim: AcetylCoA CO-ase: AcetylCoA to MalonylCoA (very 1st step)

FA b-oxid rate lim:Carnitine Acyl x-ase: AcylCoA x-port from outer to inner mitoch

membr by carnitine

Glycogenolysis rate

lim:

LiverP-rylase:cleaves a-1,4link:release G1P (stops 4G before

branch)

Glycogenesis(synth

)rate lim:

G-gen synthase: form a-1,4 glycosidic link G(from UDP-G) to G-

gen chain

Glycogen synth &

Glycogenolys

(hepatic or muscle)Glycogen-

Synthase:Glycogen:(Liver)GlycogenP-rylase


12/27

Glyconeogenesis

rate lim:F1,6biPase: F1,6biP back to fructose6P

Glycolysis rate lim:PFK1(links P to 1st C vs PFK2 which link P to 2d C): fructose6P

to F1,6biP

PPP rate lim: (PentosePhosphPathw): G6PD: G6P to 6PG-conate

Lipolysis rate lim:

"Hormon-sensitive Lipase": 3AcylG-cerol hydrolyse to G-cerol &

FA (+glucagon, -insulin); NOT to mix lipids with FA b-oxid-n

where rate-lim=carnitin

Urea cycle rate lim:CarbamoylP-

synthase1(2=Pyrimidin):CO2+freeNH4+2ATP=CarbamoylP

Pyrimidin metab-sm

rate lim:

CarbamoylP-synthase2(1=Urea):CO2+ NH2- of

glutamine+2ATP=CarbamoylP

Heme synthesis

rate lim:ALA synthase:succinylCoA+Glycine=gamma-Aminolevulinic

ascobicproline OH-lation in collagen, DOPA-to-NE(diet in

pheochromacytoma)

excess vitA//vitA (Retinol=Opsin cofactor for epithel develop): //b-carotene

depo=yellow skin

short mem\\,leg

sens\\,MMA//

\\B12: 2 functions only:MMA-to-SuccinylCoA with MMM & CH3

from B9 (Folate), then regenerate B9

B1-Thiamine a-ketoacid Ox-deCOO

B2-Riboflavin H+ mitoch RedOx

B3-Niacin H+ Ox-Phosph, NADP protein synth

B5-Pantothenate CoA (FA synth) with Thiolase (4th step in b-oxid-n)

B6-Pyridoxine trans-Amin (ALA synth)

B7-Biotin aCOO- (odd-to-propionic-to-SuccinylCoA)

B9-Folate1C-to-DNA synth (gives out CH3 by B12, then regenerated by

B12)

B12-CobalaminCH3 from N-MethylTHF-to-MMA (2 funct-ns only: both to give

CH3 to MMA and then to regenerate Folate)

C-AscorbateProline HO (collag x-link) in cell vs lysin OH-lation w/Cu+

extracell


13/27

A-Retinol Opsin cofactor, epithel develop

D-CholeCa+ferol Ca+ absorb

E-Tocoferol antiOxidant (unsat membr fat) "Antisteril vitamin"

K-'Koagul-r' COO-n of E in clott protein 2,7,9,10,CSZ to bind Ca+ to catch

canola

Canadian oil,low acid(1978)=LEAR=Low(1%)Erucic Acid

Rapeseed oil,

61Oleic(w9),21Linoleic(w6),11Linolenic,7satur(Palm,Stear,trans

)

Brassica rapa

Turnip(ka),cabbage,Brussels sprout:mustard,Rapeseed

oil(sharp-tasting glucosinolates,greenish chlorophyll,erucic

acid=heart damage)

Castor oilRicinus seed 50%=oil(90%=ricinolein=TG with unsatur w-9

Ricinoleic FA=18C, 12-OH-9-cis-octadecenoic acid

ricin

poison from Ricinus (Lat "tick") seed coat,& low concentrations

throughout the plant,grain size seed part kills adult.Castor

oil=same seed

Aceton propanon=simpest keton=carbonyl(-C=O)between 2 C

ketobodiesAcetone, AcAc and b-OH-butyrate=ketones=ketone bodies from

carbohydrates, FA & AA

spontaneous

deCOO-n of AcAc

Acetone, level much lower than other 2 ketone bodies. Unlike

the other 2, can't back to acetyl-CoA only excreted (urine) &

exhaled

FA b-oxid-n 4-step

cycle

1)FAD Oxid-n=double bond; 2)Hydr-n= -OH; 3)NAD-Oxid-n= =O

keton; 4)Thiolysis:thiol between C-2&C-3; every oxid-n cycle=14

ATP

aut-rec AA-pathology

PKU

aut-dom lipid d-er\\ LDL receptors: Famil HyperCholesterolEmia:early ateroscl-s,

infarction

acute interm

porphyriaAD def Porphobilinogen-deAminase

vit for a-ketoacid

oxidative deCOO

B1 TPP


14/27

vit for AA

degradationB6 for Aspartate-aminoX-ase

Vit for Methionine

synthaseB12 for homocysteine to Met

Vit for MMM FA(including branched)-MMCoA+MMM+B12=SuccinylCoA

a-ketoglutaric acid ketone derivatives of glutaric acid

de-amination of

glutamate=?a-ketoglutarate (-ate=anion in water from -ic acid)

starvation 1o fuel brain-ketons, muscle-FA, RBC-Glucose

muscle 1o fuelfed:glucose; fast:some FA, starv:1o:FA; vit D abuse: hyperCa-

emia: kidney Ca-fication

fat(=3-glycerids)

lipolysis

glycerid+3FA:further 3keton bodies:aceton,acetoacetate,b-OH-

butirate(mistake:b-OH-butirate not keton{R-(C=O)-R}):1omuscle

fuel,2/3brain

lipolysisboth fasting (some for muscle) & starving(marked:1o for

muscles as keton bodies)

prolonged DKA

kaussmaul to \\CO2:return pH),vomit,xx abdom pain,flu,confus-

n:lethargy:obtundation(dulled alert/conscious-s),diab.coma,brain

edema

ess-l

FA:cardioprotect

protective:a-linolenic C18:3w3=canola;

notprotective:linoleic:C18:2w6=sunflower,corn (vs18:1 w9 with -

OH on 12=Ricinoleic=castor oil)

alcoholic liver

marker//P-450://GGT

alcoholics lab

alcohol //SER://NADH:pyruvate->lactate:lactic acidosis & \\avail

pyruvate:\\G-neogenesis:fasting hypoG-emia:starving:///TG

alcoholic //TG path starving:///TG:1,3biPGlycerate:DiHO-AcetonP:Glycerol3P://TG

alcohol path & keto

metab:AcCoA

x2=AcetoAcetylCoA:HMGCoA:AcetAcetate:convert to b-OH-

butiric(b-OHB) by extra NADH(revved SER)://keto:acidos

alcohol & FA level extra AcCoA://FA synth(used only by heart)

alcohol & uric level

keto & lactic compete w/uric for kidney excretion:

hyperURICemia


15/27

alcohol & pH extra keto & lactic acids: acodosis

MMA odd propyl: MMA: succ ( if not: MMAemia+MMAuria)

MMMB12 2 functions only:CH3 to regenerate Folate & CH3 to MMA-

to-Propyl by MMM-MethylMalonicMutase

MMMCH3 to MMA from N-MethylTHF (with

MethylMalonylCoAMutase)

MMMMMCoA to succinyl-CoA by MMM (enzyme methylmalonyl-CoA

mutase)

extra from TCA fateAcAc & SuccinylCoA+thioXase=AcAcCoA; +HMG-

synthase=HMG; +reductase=mevalonic ...=CH

F-Y-Hg-maleylCoA-

fumarylCoA

f:Y;+OH=Hg-sic;+Hg-oxydase(def=Alkaptonuria)=maleylAcAc;+fumarylAcAc

hydrolase(def=Y-emia)=fumarylAcAc:AcAc+fumaric

homogentisic(from

tyrosine)

AR=def homogentisate oxidase breaks homogentisic(toxic

tyrosine byproduct):harmful to bone/cartilage,makes urine black

PKUAR:\\ f-OH-ase:newborn exposure to f:///PKetone,\\tyrosine:

mousy odor+projectile vomit(~congen pyloric stenosis!)

S #1 reaction S+HomoC=Cystathionine: C+a-ketoButirate

hepatic

encephalopathy Rx

hepatit://aromAA F,Y,W://false neurotransmitters; Rx:branch-

chain AA (they inhibit FYW)

Met fate (-SAM-

SAH)

Met+ATP=SAM(S-AdenosylMet=CH3 donor); +Methyl

acceptor+methylX-ase=SAH(S-AdenosylHomocisteine)

SAH fate+H2O=adenosine+Homocystine; +serine+cystathionine

syntase=cystathionine

HomocystinuriaAR: cystathionine synthase(def)+Homocysteine+Serine (has -OH) ://Met & homocysteine both in plasma & urine (includes

Marfan)

Homocystinuriaboth Met & Homocysteine// in serum, ~Marfan (//plasma

homocysteine:vessel damage:AMI,stroke,ment retard

cystathionine

synthase

//serum Met&Homocysteine(~Marfan):vessel

damage:AMI,stroke,retard:Homocystinuria

GSH (G-SH)

3AA=glycine+glutamate+"thion"=cysteine (rate-limiting substrate

with -SH)=Glutathion:restore RBC stressed by O2


16/27

AA-SHthiol(sulfhydryl) of Cysteine is donor of H+ in GSH(Glutathion) of

RBC, recover (reduce) by NADPH of PPP

Met

ess-l: SAM:methyl

donor:SAH:homocystein:+Cysteine+Cystathionine

synthase=cystathionine

Glutathione vs

Cystathionine

as GluGlyCyst vs HomoSer; GSH restore R-O-O-R in

RBC,diSulf bond restored by G6PD:NADPH;

Cystath=Homocyst+Ser:Homo clearance

Met fate+Adenosine=SAM,donate -CH3(with Ascorbic)=Homocystine,

+Serine=Cystathionine to clear from blood

Met fate

Met+ATP=SAM -SAH -homocyst; +Ser=cystathionine+c.lyasa

=cysteine+a-ketobutyric: propionylCoA: methylmalonylCoA:succinylCoA:TCA

SAM cycle (back to

SAM)

ATP+Met+met.adenosyl-Xase=SAM; +SAM-dep

Metylase=SAH; +5CH3THF=Met; or

+hydrolase=Adenosine+Homocys, +Serine=Cystathionine

FA 4-step b-Oxid-n

& ATP# yield

1)FAD Oxid-n=double bond; 2)Hydr-n= -OH; 3)NAD-Oxid-

n=(=O)keton; 4)Thiolysis: thiol inserts between C-2&C-3; =5ATP

(NADH=3ATP, FADH=2)

too long FA oxid-n too long for mitoch FA oxid-n in peroxisomes till octanyl CoA

G-Sorbitol-F G +aldose reductase+NADPH=S; +sorbitolDH+NAD-=F

Gal-Galactitol Gal+aldose reductase+NADPH=Galactitol

G6PaseGlyconeogenesis:liver,kidney,intestine epithelium,

absence=vonGuerke's

shuttles

3 shuttles: 1)malate for NADH 2)glycerol3P for FADH,

3)carnitine-FA (including chained); also Citric for 50% NADPH

(other 50% from PPP=HMS)

signals chain for G-

genolys to start

fasting: muscle/liver: Glucagon/E: adenylate cyclase: cAMP:

protein-kinaseA:P-ase kinase:G-genP-rylaseA (& \\Glycogen-

Synthase)

G-genolysis @

fasting: rate-limitingG-genP-rylaseA

G-genesis (fed) G+G-kinase=G6P;+PGmutase=G1P;+UDP-G-

rylase=UDP-G(+UDP+PPi);+G-gen synthase(rate-lim,insulin-


17/27

enhanced):a1,4 link

G-syl 4:6 X-aseX-fer 5-8 G from non-reducing linear end to branch point as a-

1,6 link

G to G-genpostprandial="fed"://G:insulin//:hepatocyte//G-gen synth:granulew/both enzymes P-rylase&synth &membr G-genin(Tyr-to-G

reducing end)

G to G-gen & back

to G

60K dendrimer G-gen a1,4&a1,6=12:1 in hepatocyte granule

(8% of liver weight, 1% of muscle)starts degrn 4h after meal,

depletes in 12h

Glucogenin

prime G-gen bind covalently reducing end of 1st G from UDP to

-OH of Tyr residue, then 7 more, but 9th added by reg G-gen

Synthase

Gluconeogenesis

enzymesPC-PEPC-F1,6biPase(rate lim)-G6Pase(vonGierke)

galactose to G=G-

neogenes

lactose+lactase=G+Gal;+galactokinase+Gal1P;+GALT+UDP-

G=UDP-Gal+G1P;+PG-mutase=G6P;+G6P-ase=G

statins

iHMG-CoA reductase(rate-limiting step in cholesterol

synth:AcAcCoA:Mevalonic:Cholesterol):sole major cholesterol-

lowering drugs

major 4 classes of

P-lipases

A1:cleaves SN-1 acyl; A2:cleaves SN-2 acyl; B-both SN-1/SN-2;

C:before P=DAG+P-head; C:signal X-ductor (2nd mess-r

Inositol3P)

Phospholipase D Phospholipase D - cleaves after P=phosphatidic+alcohol

HGPRT //uric:gout,retard,selfmutil-n:Lesch-Hyhan

GALTaccum Gal://galactitol(//osmos:damaged

lense,CNS):Galactosemia

f-OH-ase accum fenylKetone,\\Y:PKU

homogentisic acid

oxidase

not oxidized homogentisic=toxic tyrosine byproduct:harmful to

bone/cartilage,urine black:Alcaptonuria(=ochronosis)

fumarylAcAc

hydrolase

AR://Y:cabbage odor,cirhosis to hepatocellular carcinoma:

hereditory Y-osis

hepatic F-kinase mild Essential F-uria

Aldolase B //F takes all P:\\ATP:weak RBC:hemolysis,//AMP:gout:hered-ry


18/27

F intolerance

Ascites in

alcoholosm//hydrostat P in Splanchnic capillares

bilirubin //: uncon-&conjugated

\\GlucuronylX-ase(massive RBC destruct-n): // unconjugated;common bile block: // conjug; hepatocyte damage: // both

any reactions=3

substancesSubstrate+Enzyme=Product

3 reactions metabolism=anabolism & catabolism, mutation

MMA comes from

Isol,Val,Thre,Met,Thymine,Uracil,Cholesterol,odd-chainFA:

propionyl-CoA: Methylmalonyl-CoA; +Methylmalonyl-CoA

mutase=MMA

AcAc:.....CHextra from TCA:AcAc & SuccinylCoA+thioXase=AcAcCoA;

+HMG-synthase=HMG; +reductase=mevalonic ...=CH

HMG-CoA

reductase

3-hydroxy-3-methyl-glutaryl-CoA reductase,8-transmembrane

domain anchored in membrane of ER (endoplasmic reticulum)

HMG-CoA lyase Cholesterol-HMG-AcAc-23ATP

branch-chain AA

metab,d-seDehydrogenase: in muscle only, deficit:Maple Syrup urine d-se

branch-chain AA:

V,L,I degrad-n

3 essen-l: Val, Leu, Iso; degrades NOT in liver but muscle by

branched-chain AA-DH-ase (if not:Maple syrup)

maple syrup urine

disease

V,L,I:branched-chain -keto acid dehydrogenase complex of

5:Thiamin,FAD,NAD,CoA,Lipoate (same as PyruvDH,a-ketoG-

DH)

Niacinvit B3=nicotinic acid=pyridine(heterocycle:benzene,1C substit byN)-3(=3d place from N)-carboxylic acid; precursor for

NADH,NADP,NADPH

Niacin vs

nicotinamide, norm

g/day,extra?

identical as Vit B3:prevents pellagra; but niacin=conversion

side-effects:flushing,\\cholesterol; nicotinamide:>3g/day liver-

toxic;

pandemic def-cy d-

se

4Vit def-cies: ABCD: A-retinol, B1=thiamin (beriberi), B3=niacin

(pellagra), vit C (scurvy), vit D (rickets),

2 forms of B3 vit B3 Niacin=pyridine(benzene w/1N hetero-ring) +COOH @3d-


19/27

pos-n from N; if +NH2 on COO=carboxamide group

CONH2=nicotinamide

child's fear of

procedure & pain

pain \\ by diversion (parents presence // reaction by displaying

concern)

autistic infant don't visually track pediatrician

Mobiuscongenital facial diplegia+ocular

palsy+clubfoot+syndactily+mentally retarded

reactive attachment

dr of inf-cy

severe parent-child bond interruption(foster home or immature

parents):malnutrition:die

Rettprecipitous development deterioration after 6mo norm

development

autism avoid human contact

infant Colic cry >3h/d >3d, Rx:hold,\\stimul-n,*spasmodic

blots ("U4")

West:prot in mix, SW:prot-radiolabl DNA, S:DNA-DNA epidem,

N:RNA-radiolabl DNA (as letter U on map)

CVS vs CVP

(Chorionic Villus Sampling)16-18 wk amniotic fluid

cells>FISH,other vs Centr Vein Pressure

FISH(fluoresc in situ hybridization)DNA probe labeled w/fluoresc,

uneuploidy, delition,structur abnormalities

Fragile X:

Behavioral:

shy Autistic: hand bite/flap, Hyperactivity, \\attention,

LanguageDelay, Perseveration (action/word repetition), \\eye

contact

Fragile X: Physical:vision\\, long face,ears&testicles,Flat feet,High palate, Hyper-

extensible joints, \\ muscle tone

RFLPRestriction fragment lenth polymorphism; restr endonuclease

recognize unique RFLPs pattern on DNA near centromere

Savitski gene "AT-gene": Ataxia+Telangiectasia

TDF

Testes Determ Factor=protein coded on SRY gene of Y

chromosome; unfluenses gametes to develop into Testes (if

TDF deficient:stay as ovaries)

X-link: 10Recessive +2

Duchenne,Lesch-Nyhan,Wiscott-Aldrich,HemophA,B,G6PDHdef, chr granulomatos,aGglobEmia,


20/27

Domin colorBlind,DI,Fragile X (Hunter,Fabry:domin)

Wiscott-Aldrich1 of 10 X-link recessive:

immunodeficiency+thrombocytopenia+eczema

?meios comb-nsfrom?possible

2 from 4

n2=46chr-

som(23mom+23dad

)

synth:(23chrom mom x2 chromatides w/1centromere=46chr-

tides)+23chrom dad:synth=46chr-tides,Total:n=4,chr-

somes46,chr-des92

C1 estherase

inhibitor def-cy clinicrecurr colit atacks+laringoedema=AutDom Heredit Angioedema

meiosis 1

1 c-mere for 2 sister chromatides: 46ch-

som(23m+23dad):meios1:each chr:2sist chr-tid(duad),2 homol

duads=tetrad:recomb:align equator

plate:pulled,cytokines,meios2:

meiosis 2

2 c-meres(1 for each sister chromatid)=2 sep-ted chr-

tides(monades)pulled:4 cells 1n=23chr-id=23chr-somes each

with 2 Allele comb-ns from 4 possible

mitosis

each sister cromatid got own centromere (in meo1 only 1

centrom for 2 sist,meo2 each sis get centomere but after alleles

separ-d)

Meiosis vs mitosi

cetromere not dubbed:duad:synapse in tetrad:crossover,pulled

in 2 duads(mei2:pulled in 2monads) vs mit:each cr-id gets

centromere

5 deletions

5:Cri-Du-Chat, 11:Wilms'(UTI tumor)

15:Angelman(mom)/Prader(dad), 22:DiGeorge (=Thymus

aplasia:\\T-cell,hypoprathyroid: \\PTH)

DiGeorge chromosom 22 deletion: Thymus aplasia:\\T-cell,hypoprathyroid:\\PTH

2 translocationsReciprocal(between non-homolog in meiosis 1) vs Robertsonian

(long-to-long with smalls lost)

TDF on ovariesTestes Determ Factor on Y: gametes become testis; w/out: stay

as ovaries

SRY vs TDF

SRY is gene for TDF; Sex-determining Region on Y encodes

TDF (protein binding in gametes to DNA for Xscription: ovaries

Xform in testes)


21/27

SRY vs TDF

SRY=intronless gene encodes Xcript-n factor=DNA-binding

protein=Testis Determining Factor=TDF=SRY protein, initiates

male sex determ-n

SRY vs TDFMutations

XY female w/gonadal dysgenesis=Swyer sdr; X-location of part

of Y with this gene to X =XX male sdr; 1Y+multiple X:(XXY,

XXXY)=males

SRY-to-X chrom-l

X-location

male phenotype (look) but female genotype (XX):SRY in 1 or

both X. These males are infertile

muted SRY on Yfemales with an XXY or XY genotype, but defective (=mutated)

or no SRY on Y

gender verification

Int'l Olympic Com-tee 1992:"No SRY female allowed". Summer

Olympics1996:detected ruled FP & were not disqualified.2000:no screen

AIS androgen insensitivity sdr: XY+SRY+female phenotype

why men more

Parkinson/SchizoSRY makes a protein controling concentrations of dopamine

deletions3=codon deletion(3extra:codon expansion),not 3:frame

shift,large :Exon skip, wrong read:missense

WAGR 11th chromosome:Wilm,Aniridia,Genital\\,retard

extra 21 chromos

probabilitymom age 20-24=1/1562; at 35-39=1/214, above 45=1/19

survived 3-somias:

13,18,21;

polydactyly,cleft lip/palate,Rocker feet,dye 1st year; retard

ment&growth,low ears,micrognatia,Rocker feet,dye 1st year;

Down:retard,short

Fragile X, 45,X(XO);

47XXY(XYY)

more boy, retard, large testis; Turner:short+ovary dysgenes;

Klinefelter:tall,small penis(hypogonadism),testicular

atrophy,eunuchoid,may retard

mut-ns: point vs

frameshift

3 point: silent,missense(HbS),nonsense(Thalas) vs frameshift:3-

deletion(CF); 4-incertion (hexoAminidase: Tay-Suchs);

DNA & mRNA

strands sences

DNA1=sense=non-transcribed; DNA2=antisense(compl-ry to

sence)=transcribed=templatesense mRNA(compl-ry to

antisence)proteins


22/27


23/27


24/27

PTA sourse

Most spontaneous (possible genetic, teratogens as

virus/drug/chem). ~50%=chr-some 22q11 deletion. Cardiac

neural crest contributes AP septum

ostium=foramen in

heart

in septum primum: for.secundum, in septum secundum:

for.ovale

Teratology study of abnormalities of physiological development

Birth defects %

3-5% of all newborns, over 20% of all infant deaths. 7-10% of all

children require extensive med.care to DS & Rx, 65% no known

cause

inner mass fatedivides: epi(further into ecto-,meso-

,endo=entoderm)+hypoblasts

kids 3 age divisions infancy - toddler (learns to walk=12-18mo) - childhood

Preeclampsia

placenta disfunction or other: general-d damage to maternal

endothelium,kidney(protein in urine),liver: 2ry // vasopressive f-

rs: //BP=PIH

PIH

pregnancy-induced hypertension as result of Preeclampsia

(placenta disfunction:general-d damage to mom's

endothelium,kidney,liver)

partus onset birth (labour,parturition) starts from contractions: sudden, withwater break, or gradual // of uterus contraction (long muscle)

partus stages

contractions, path(cervix fully dilated, desire to push), afterbirth

(placenta expelling); total:13h 1st-timers("primiparae") & 8h 2nd

birth

water breaking amniotic sac(amnion+chorion) rapture

contractions phases

latent:cervix effeces 3cm;active labour:freq 3-4/10min(1min

contr+2min rest);transition:dilation 8-10cm,freq1 in 2min,70-

90sec each

emotional phases of

transition

transition is most intense(but short): exited-focused-"self-doubt

bouts"(giving up)

induction indication

& Apgar

indic-n for induct-n: 42w w/out labour(contraction); Apgar

=assesement score (HR,resp,m.tone,skin color,response on

stimuli) @1 & 5 min

breech, 3 "f" not head 1st but battock or leg; types:"Full":buttocks,

"Frank"(feet to ears), "incomplete"("Footling"):1or2leg 1st,


25/27

transverse(arm 1st)

posterior baby pos-

nface fwd

blood loss @ partus 500ml

menstr cycle 2

phases

1.Estrogenic=Mitotic(//cell#)=Proliferative

2.Luteal=Secretory=Hypertrophic(//cell size)=apical

move/Glycogen accum in glandular cell

menstr cycle 3

stages

3 stages(divid 2phases):Period=d1,

Ovulation=d14("mittelschmerz" if pain), Premens d28(glandular

degeneration)

implant-n day & cell#

7div-ns in 7days from ovul-n~128 (2power7)=cell

blastocyst(inner mass,trophoblast,blastocele=cyst) burry during

24h, d11:maternal circul

days # for implant-

burry-circulationblastocyst: 7-8-11

FSH,LH,hCG,Prolac

tin,Oxitocin

FSH:testes/ovary func-n;LH:Progesteron;hCG keep

LH;PL(Prolactin):menstr,lact-n; Oxitocin:contract breast(milking)

& Uterus(orgasm)

hypothalam:GnRH:/

/?

hypophis://FSH(//testes:sperm; follic:ova) &LH(theca:Estradiol,Leidig:desmolase:Ch-ol-to-

pregnenolon...:testosteron

Inhibin vs Activin

both regulate mens: Inhibin//FSH: //Inhibin: \\FSH; 2 Inhibins: A-

type peaks @mid-luteal; B:2 types: peak @mid-follic & ovul-n;

Activin=*Inhibin

Estrogen

4 rings: 3 w/6C (A,B,C), 1 w/5C (D); 1)if 1OH on A &1 keto (=O)

onD EstrOne; 2)-OH on A&D=EstraDiol; 3) 1OH on A+2 on

D=EsTriol

estrogen 1o synth

mech-m

Ch-ol:ovaries'theca interna:androstenedione:cross basal memb

to granulosa cell:testosterone+arom-ase=Estradiol(2 -OH A,D

ring,strong)

estrogen 2o synth

mech-m

liver,adren,breast: androstenedione+aromatase: estrone

(ketone=O on D-ring,weak)

Estrogen path

FSH+LH:1o:ovaries' theca

interna:follicle+corp.luteum+placenta:estradiol;2o:liver,adren,bre

ast:estrone(>estradiol postmenop)


26/27

Estrogen for women

vs men

women:2ry sex characteristics; men:brain mascul-n,sperm

matur-n, libido

oral contraceptives Estrogen \\ circulating FSH & LH

Estrogen loss bone minerals\\,45%alveoli\\,cholesterol//:cardiovasc d-ers

breast cancer

hormonal Rx

80% breast cancer need estrogen to//("hormon-

receptor+","hormon sens-ve"):Rx:estrogen suppression

hormonal Rx vs

horm-replacem

hormonal=anty-estrogen; replacement=estrogen 0.3-0.6-1.2mg

(Premarin+Provera="PremPro"),topical avoid liver 1st

pass:\\clotting

Leydig interstitial

cell

small eosinophilic (from //SER) cells adjacent to outsid of

seminiferous tubules: testosteron \\ LH

Leydig interstitial

cell

pituit:FSH://Leyd.membraneLH-

receptors;FSH:activatesLeyd.cholesterol desmolase:cholest-l to

pregnenolone(testosterone synth)

placenta 2 parts

fetal Chorion Frondosum (vs non-placental but surrounding

fetus avascular Smooth Chorion)+maternal Decidua Basalis(vs

Capsularis around fetus)

preeclampsia 20wk

shallow placent:inflam:vasoactiv:PIH(pregnancy-

inducedHT)+signif-nt(>300mg/d)urine protein (noprotein=Gestational HT)both=emergency

PIH vs GHT

shallow placent:inflam:vasoactiv:PIH(pregnancy-

inducedHT)+signif-nt(>300mg/d)urine protein (no

protein=Gestational HT)both=emergency

postpartum pituitary

ishemia

med eminence+ant.lobe(post=neuro:ADH,Oxytocin) no arter,

only Long Portal veins between Sup(1o) & Inf(2ry) hypophyseal

plexi

pituit cells by lobes

1)ant:basophil(GnTH=FSH+LH,Thyrotr:TSH,Corticotr=ACTH),ac

idophil(Somatotr=GH,Mammotr=PL);

2)post:Oxytocine,ADH=Vasopressin

pituit cells of

intermed lobechromaphob(stem,degranulated,supporting=folliculostellate)

milk synth vs

milking hormons

synth:Rutke pouch:ant.Pituit.lobe:acidophil:mammotrop cell:PL;

vs hypothal:SON,PVN:Oxitocin:poster(neuro)Pituit.lobe:Hering

granules

milk synth vs inhib hypothal GNRH:anter pituit acidophilic mammotrop cell:PL, inhib


27/27

hormons by PIH=DOPA

Oo- & spermato-

genesis start

oogenesis:meiosis starts before birth,arrest at prophase1 till

puberty; spermatogenesis:starts only at puberty

2 principalgonadotropins

LH,FSH (2peptide chains: nearly identical alpha chain & specificbeta w/disulfide bonds) & 3d placental hCG

Sperm cell mitosSpermatogonia(primitive germ):repeated mitos to Prime

spermatocyte

Sperm cell

w/crossover

1ry spermatocyte:DNAReplic-n:1st divis-n(Meios=Reduc-

n):paired homolog(NOTsister)chromatides:Transposit-

n=crossover(Meios1Prophase)

Sperm cellw/haploid

2ry spermatocyte:2d meiot div-n=4 small spermatides w/haploid

chromosome# seminiferous tubules:spermiogenes(matur-

n):spermatozoa

Menses cycle peaks

Estrogen peak before Ovul-n:+feedback to

hypothGnRH(pulsatile)://hypophLH:Ovul-n,(FH peaks

too);Progesteron(//secret)peaks before mens

3 Estrogens

common:4rings(ABCx6,Dx5) with OH- on A; Estrione=1OH- on

A(+ketone=O on D);EstraDiol (2 OH- onA&D), Estriol (3 OH-:

1onA,2 onD)

Menses & Estrous

cycles

estrous:endometrium reabsorb endometrium (if no concept-n),

menst-shed it:Greate Ape only:includes

human,chimpanzee,gorilla,orangutan)

Documents

Usmle Medical Biochemistry