MEDICAL BIOCHEMISTRY

USMLE step 1 Last moment revision

www.gims-org.com

Also included harmone related topics

Terms
Glucosid

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

3 G-genoses with \\ liver P-rylase, liver debrancher, vonGierke, fasting G blood glucose norm 70-90mg/dL from 1)diet 2)fasting Cori Cycle for range gluconeogenesis from Lactate 3)Glutamine of muscle wasting TCA:extra AcAc+SuccinylCoA+thioXase=AcAcCoA; +HMGsynthase=HMG; +reductase=mevalonic:Chol-ol vs TCA:extra citric:AcAc:Malonic:FA Glycerol+H2O2=DHA(aceton OH,=O,OH)+GA(aldehyge OH,OH,=O) Gal-to-G: Gal+Gal-kinase=Gal1P; +GalT+UDP-G=G1P; +Gmutase=G6P:G6pase=G Hered-ry Fructose Intoler(aldolaseB def://F1P) * Dietary FI (F malabsorp-n) enterocyte FK def:bloat,diarrh,constip-n vs Hepat FK=Clinitest

extra AcAc path

Glycerin mild oxidation= G1P path

HFI vs DFI vs EFI

aldolase A vs B def- A:G-neogenes(GA3P+DHAP=F1,6-biP):severe hypoglycaemia; cy vs B:F+Fkinase=F6P,+aldB=DHAP+GA(GA+3ose kinase=..) /ketoacids: \pH: kaussmaul="Produvka" to \\CO2 to /pH),vomit,abdom pain,flu,confus-n: lethargy:obtund-n/dull alert/conscious),brain edema:coma glycerid+3FA: further 3keton bodies: aceton, acetoacetate,bOH-butirate (mistake:b-OH-butirate not keton{R-(C=O)-R}):1o muscle fuel,2/3brain brain-2/3 ketons,1/3 G, muscle-FA,including branched, RBC-G, immune cells & kidney-Glutamate in fasting: as muscle wasting:1o fuel, but not in starving: saved for RBC only! both fasting (some for muscle) & starving(marked:1o for muscles as keton bodies)

prolonged DKA

fat(=3-glycerids) lipolysis

starvation 1o fuel

Gluconeogenesis

lipolysis

brain fuel @ starv-n 3 ketobodies Gluconeogenesis enzymes PC-PEPC-F1,6biPase(rate lim)-G6Pase(vonGierke)

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 debrancher deficiency G-gen 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; ENH2=a-ketoacid (vs b-keto in FA)

Apo100 & 48 from Apo100 from liver, 48 from intestine liver & ketones for fuel why folate \\ in alcoholics Liver canNOT use AcAc as cardiac: SuccinylCoA+AcAc+AcAcCoA(thio)X-ase=AcAcCoA; +HMGsynthase=HMG; +lyase=AcAc folate (B9) loss in urine/stool (bear offset loss providing extra folate!)

P-lat-n by Insulin vs fed:Insulin deP-lates(activates)P-ase:G6P loose P:bond to Glucagon glycogen chain:fasting:Glucagon P-lates(activates)P-kinase NADPH source & target most ""&"+"(basic)AA from PPP for reducing stressed RBC Glutamine:"-"=acidic:travel farthest in e-phoresis; most"+"=basic:Arginine remain at anode("-"pole giving ""electrons) adipose:hormon-sens lipase:TG:FA; mito:FA b-oxidn:AcCoA:AcAcCoA

ketobodies source

hepat GlycogenP-rylase; G6P-tase(Glycogen store d-se); FA b\G,/k; \\\G,/k; \\G,\k; oxid-n block; FAcylCoADH=AR (aut/reces) MCAD in homozig /diCOO+\\G,\k N.Europe kid fasting:FA:AcylCoA:carntin shuttle:b-oxid:keto(save G for brain);N.Europe aut-rec homozig kid can't utilize own fat:G<20:seizure:20% SIDS prim or 2ry (too much AcylCoA accumul-d) carnitin block

MCAD

\\\keton

no/G,hyperAmmone Ornithine X-carbamoylase def mia,/diCOO 5yo: gastroenterit: seizure:coma Hepat Glycogen P-rylase

fasting overnight vs Glycogenolys:Gluconeogenesis vs 2d Proteolys:lactate:G6P:G:FA:keto norm fasting G=4.2-6.1 (64 - 128 mg/dL) vs 20%MCAD(white Glucose norm level kid):SIDS: <0.11mM (20mg/dL); urine:norm=0 (overflow when vs SIDS DM blood>250) energy for protein synth energy for cardiac muscle GTP

FA b-oxid-n to ketone bodies

galactose to G=G- lactose+lactase=G+Gal;+galactokinase+Gal1P;+GALT+UDPneogenes G=UDP-Gal+G1P;+PG-mutase=G6P;+G6P-ase=G AR: GALT def: excess Gal-to-galactitol (polyol=sugar alcohol):act as sorbitol:// plasma osmos:damaged lens,CNS,liver toxic: retard,cirrhosis,ren damage, benign AR:+"urine Clinitest"(detect all reducing sugars=all but "G+F" sucrose)

Galactosemia

Gal1P excess Gal-kinase def

Gal//: benign:\GalK: /urine Gal:Clinitest, benign & toxic //Gal tox:GALT(retard,cirrhos,renal); vs F//: vs //F benign:Essential(\hepaticFK), tox:Heredit(\AldB):cirrhos reducing sugars F metab-m all monosugars with free aldo- (not cyclic), NOT sucrose (G+F) sucrose+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 Essential F-uria hered-ry F intolerance sperm in seminal vesicles AR: hepatic fructokinase def-cy(+Clinitest),less severe than hereditary fructose 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 excess F traps P:cell \\P:\\ATP:RBC hemolysis, //AMP(accum& cell P n)://purines://uric:gout; Rx:table sugar(sucrose)-free diet seminal tubules:GG +aldose reductase=Sorbitol; +sorbitol DH(DeHydrogenase)=F Sorbitol-F

tissues w/aldose reductase

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

DM:///G:///Sorbitol:// lens:cataract; retina:microaneurism&pericytes osmos:? destructionSchwann:perif neuropathy Gaucher vs Guerke [gosh'ei]: \\cerebrosidase:cerebrosid accumul-n (brain OK) vs \\G6Pase:no Gluconeogenesis from hepat.glycogen 20yo:cant utilize muscle glycogen(liver can):on exercise:muscl cramps+hematuria Glutamine(immun,kidney,guts),G(RBC),1/3G+2/3ketone(brain), FA(muscles) unRx DM(often 1st time DS): hyperglycemia but starvation+stress(infection)=hyperketos+acidos:denatur, fruity smell=nail polish remover \\\insulin(unRx DM mostly Type1)+//stress hormons(infectn):///ketobodies:pH\\:severe acidos(6.9-7.1),under 6.7=permanent denatur:death xx tired,aceton breath,/// thirst+const urin-n,muscle waste: ///weight-loss,oral/genital thrush(bact on xx glucose),aggress,agit-n,irrit-n b-cell:insulin:6min in blood: tyrosin-receptors: GLUT-4 synthes:takes glucose from blood; after 6min \\\insulin: \\Glut4:no Gluc uptake unRx DM Type1:beta-cell \\insulin: in 6 min \\insulin://glucagon:mostly act on hepatocyte:glycogenolysis:keep sugar in blood for RBC in 6min blood insulin\\:no Tyr signal:\\newGLUT4 synth & old\\:\\G uptake:sugar stays in blood & //:starv-n:ketobodies:\\pH norm7.35-7.45; :DKA:severe acidos 6.9-7.1 rapidly in 24h; under 6.7:death (permanent denatur-n of blood proteins)

McArdle

fasting fuel

DKA=after 24h starvation

DKA

DKA symp

Glucose uptake mechanism

glucagon role

if b-cell inhibited norm pH,severe acidosis,death

insulin-independent not usual GLUT-4, but GLUT-?:brain,liver,b-cells,intestine cells urine sugar ///gluc:tubule SGLT overused:spill to urine:take water:water loss (=Diabetes):dehydration:thurst sorbitol isomer:osmotic diuretic,weak renal vasodil-r,sugar alcohol(polyol)~sorbitol but lose H+in sol-n=acidic:needs bicarb

Mannitol,Mannite,M

anna Sugar Mannitol

to norm pH IV \\ acutely raised intracranial P:fiter,no reabs:pulls H2O in urine:\\POsm:ECF:ICF:\\brain cell edema; >20g=kids laxative

Mannose-G-Gal vs 3 aldoses(=O on 1stC):Man:2d, G:3d, Gal:4th -OH on LF side(up); vs F=ketose (=O on 2d) # of G for Palmitic synth eachG gives 2AcetylCoA x4G=16C

ATP # from Palmitic C16={8AcetylCoA(each=2CO2&2H2O=12ATP)=96ATP; addit-ly oxid-n 7NADHx3ATP+7FADH2x2ATP=35ATP}=131 aldoses Hexoses aldolase B def galactokinase def 1stC=O: (2d=ketose F) G:3d -OH left-up; Mannose:2,3; Gal:3.4 Hered Fructose Intolerance (aldolase B +fructose-1P =glyceraldehyde+dihydroacetone) galactosemia

\PPP(=HMS-hexose-mono shunt): \\NADPH synth: no gl6P Glutathionine restored: // radicals: \RBC defense: if Oxid stress: dehydrogenase def hemolitic anemia ALT:AST=1:2 alcoholic "alphabetic" hepat Alcohol(ALT:AST=1:2, toxic=Fatty Liver); Drug-induced: fever,rush,arthralg,/eosinophil; WD:\\cerulloplasmin+KayserFleischer ring; HepB degrades NOT in liver but muscle only, by "Branched-chain AADH-ase", if deficit: Maple syrup in urine vonGierke:aut.recess:accum glycogen:\\G,1yo /// Uric,lactic,TG,Ch-ol,keto(from FA),liver damage:fail:bleed diates, liver adenoma //uric:gout,retard,selfmutil-n:Lesch-Hyhan (1 of 10 X-link) accum Gal://galactitol(//osmos:damaged lense,CNS):Heredit Galactosemia accum fenylKetone,\\Y:PKU not oxidized homogentisic=toxic tyrosine byproduct:harmful to bone/cartilage,urine black:Alcaptonuria(=ochronosis) AR://Y:cabbage odor,cirhosis to hepatocellular carcinoma:

Hepatic d-ers

muscle branchchain AA-DH \\

G6P-ase \\

HGPRTv \\ GALT \\ f-OH-ase \\ homogentisic acid oxidase \\ fumarylAcAc

hydrolase \\

hereditory Y-osis

hepatic F-kinase \\ mild Essential F-uria Aldolase B \\ Ascites in alcoholosm yellow greesy enlarged liver //F takes all P:\\ATP:weak RBC:hemolysis,//AMP:gout:hered-ry F intolerance //hydrostat P in Splanchnic capillares #1alcoholism:steatosis=fatty liver (less:CCl4,DM,obesity,malnutrition):lipid accumul in hepatocyte displacing nucleus

lysosomal storage AR:accum GAG, sphingolipids,G-gen(Pompei d-se); 2 d-es exceptions:not AR but X-linked:Fabry & Hunter mistake@Golgi post-translational modif-n of enzyme:no lysosomal storage Mannose P-lation:no receptor bond/pinch/vesicle X-port/fuse d-es w/lyzosome iHMG-CoA reductase(rate-limiting step in cholesterol synth:AcAcCoA:Mevalonic:Cholesterol):sole major cholesterollowering drugs major cholesterol-lowering drugs=iHMG-CoA reductase(ratelimiting step in cholesterol synth) vs antiFungal 3-hydroxy-3-methyl-glutaryl-CoA reductase,8-transmembrane domain anchored in membrane of ER (endoplasmic reticulum) Cholesterol-HMG-AcAc-23ATP

statins

statins vs Nystatin HMG-CoA reductase HMG-CoA lyase

Hyperlipoproteinemi 1:chylo, 2:LDL, 3:dis-b("remnant d-se"), 4:VLDL, 5=1+4 as (chylo+VLDL) CH & fasting fasting do not effect Cholesterol (all in HDL); norm CH<3% of chylomicron; fasting is Unnecesserary for CH measure LDL=CH-HDL-TG/5, where TG // from diet chylomicrons: LDL measured in fasting 1of 5 Lipoprot:Liver:nascent (apoB100, no apoC2&E yet) 3080nm,>97% of blood Chol-ol(<200); HDL gives apoC2&E=mature,(-)TG=IDL Liver:b100(nascent)+HDLapoC&E=mature; +muscle & adipose capillary LPL:--TG; HDL:+ChE,take back apoC(keep E),TG&P-

LDL & fasting

VLDL

VLDL exchanges

lipids=IDL VLDL vs Chylomicr liver synthes-d endogen fats 30-80nm with 1/5of total blood TG,broken in blood to LDL(Friedewald estim-n) vs exo-(diet) fats

LDL on HMG CoA Ch-rol uptake:\\LDL-rec-tor synth(=B100r-or,recycles, w/clatrin): reductase \\HMG CoA reductase x-cription: \\ Mevalonic (1st in C-ol synth) Cholesterol (norm<200-border-240-high)>97% as VLDL, <3% diet chylomicron, 3,500 cal/lb=day of hard physical labor=3.5lb of fish or 19lb of carrots

Human fat=

A1 & 2 (Acyl):cleave 1st or 2d; B-Both; C="Signal X-ductor (2nd major 4 classes of mess-r):before P=DAG+P-head= Inositol3P, D-after P-lipases P=phosphatiDic+alcohol I-cell d-se enzyme for lysosome can't P-late mannose residue while in Golgi:lysosome can't degrade:accumulate aminosugar(G&Gal-amines)+acid sugars(Glucuronic&iduronic) long chain chondroitinS(most abundant):cartilage (w/collagen2); heparanS:"-"GBM (w/collag4); heparin:*coag; hyaluronic:synovial fluid; dermatanS:heart valve AR:\\a-iduronidase;lyzosomal accum dermatanS,heparanS:severe retard,corneal clouding,vessel fat,perif leukocyte vacuoles,Lamin-d mito XR:iduronate2sulfatase(I2S)severe progressive life-limiting //facial features,//head,abdomen,liver,spleen,\\hearing,thick heart valves:\\CO,COPD, sleep apnea Sph-myelin(NS membr),cerebrosid,gangliosid [Sphingosine+FA=ceramide]+P-choline

GAG structure

GAG types

Hurler

Hunter Hunter sympt Sphingolipids Sph-myelin structure

ceramid+...G or Gal ..+G or Gal=G-/Galacto-cerebroside; or oligosaccharide +oligosaccharide=ganglioside Niemann-Pick Gaucher def spingomyelinase:accum sph-myelin:bubbly macrophages & neuron,lyzosomal zebra stripes, retard,hepatosplenomeg [gosh'ei] def G-cerebrosidase:accum G-cerebroside:crumble

newspaper(=fibrillary) in macrophage,//serum acid P-ase from macrophage Krabbe Galactosyl-ceramidase:abnorm myelin:retard,CNS histiocytes(multinucleated globoid) def a-GalactosidaseA:accum ceramid-3-hexoside, X-linked recessive inherited lysosomal storage:skin angiokeratomas,HT,ren fail AR: liver&kidney G-neogenesis: G6P-ase def:accum G6P:accum G-gen:1yo://uric:tubule\\\excret uric(gout) & lactic(acidosis) give F,Gal or Glucagon: NO blood G// (missing G6Pase:1yo://uric) a-1,4G-idase=acid maltase=only G-genosis lyzosomal storage d-se: accum G-gen in lyzosomes in many tissues: G-gen depo in heart:restrictive cardiomyopathy ///blood protein synthesis:depo protein fibrills in heart(restrictive cardiomyopathy:\\CO) & kidney(fail) AR:4-nucleotide insert-n:frame shift in hexoAminidaseA://GM2=Sph-lipidos;norm birth:6mo:blind,cherry macula,retard,lamellar lyzosom hexoAminidaseA \\ :Sph-lipidos:accum GM2 in ganglion=gangliside:swallen retina ganglions="macular Cherry Spot" macular change,seizure,spasticity,mental retard-n Tay-Sachs:hexoAminidaseA \\ :Sph-lipidos:accum GM2 in ganglion=gangliside:swallen retina ganglions="macular Cherry Spot" point mutation(silent,missense,nonsense), frameshift:insrtion/delition not 3 nucleotides(insert4 in hexoaminidase=Tay-Sachs); AA lost(as F in CF) Hurler:mucopolysaccharidosis:heparan & dermatan sulfate & Sunfilippo:heparan s vs GM2 ganglioside in Tay-Sach Gaucher's [gosh'ei],Niemann-Pick

Fabry

von Gierke

von Gierke load test

Pompe Pompe & heart myeloma

Tay-Sachs(NO hepatosplen)

Tay-Sachs

Tay-Sachs sympt

gangliosidosis

mutation: 3 types

laminated mito vs lamellar lyzosome lipid storage disorders

Gaucher Newmann-Pick

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

1of10X-link: gout mom:norm birth,late sit,most never walk,//uric Leschacid:gout,stone(allopurinol!),retard,~palsy,~Huntington,selfmutilNyhan:boy\\HGPRT n Foam cell P-Lipids Sphingolipid parts yellowish tendon depo FH Nieman-Pick (Glycerol+2FA+P=Phosphatidic Acid)+Serin,Inositol,Ethanolamin,Cholin(Lecithin) (Serin+2FA+P=Ceramid)+Cholin(Sphingomyelin) Greek: yellow=xanthoma=xanthomata=xanthomatosis):yellowish cholesterol-rich depo in tendons Familial hypercholesterolemia 2:genet dis-r: //LDL, //"bad cholesterol" 1)mut LDLR gene encoding protein(LDL rec-r (removes LDL from the circul-n); 2)apolipoprotein B (ApoB)

FH reasons

def LDL r-tor (recognizor of B100 of VLDL synthesized in liver) Xanthoma+Xanthe in Clathrin pit: \\endocytos of Cholesterol: cholesterol accum mia+corneal arc outside of cells allopurinol physostigmine iXO (Xanthine oxidase): reversible non-comp-ve inhib of XO+purin=hypoxanthin, +more XO=uric iCholinestherase:AcetylCholin// (reversible non-comp-ve inhib)

organophosphates iCholinestherase:AcetylCholin// (irreversible inhib) VLDL & chylomicron main part LDL estim-n

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

Freidewald: LDL(2.4-4)=Tot Chl(3-5.2 or <200)-HDL(0.71.9,fem0.9-2.4)-VLDL(=1/5 fasting TG)

Ch-ol ("Total") ## & norm <200(5.2)<border<240(6.2)<high; need for 4: need for bile,VitD,corticosteroids,sex hormons Sterols phytosterols(plant) & zoosterols (animal:cholesterol,steroid hormones); diet phyto block zoo absorption:reduce cholesterol

excess Lypofuscin age

excess Hemosiderin heart fail:pulm capillary:macrophage Hemos-n laden("heart (Fe-store) 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

ochronosis=alkaptonuria(block PA-to-Tyr: // homogentisic 38yo heredit acid:degenerative arthropathy 40th, X-ray:lumbar disc degenerjointpain,blue ears n & Ca+-n Heme synthesis in Gly+SuccinylCoA(ALA-synthase)=sigma-ALA; +Porphobilinogen RBC synthase=P-gen; +Ferrochelatase=Heme Hered-ry Fructose Intoler(aldolaseB def://F1P) * Dietary FI (F malabsorp-n) enterocyte FK def:bloat,diarrh,constip-n vs Hepat FK=Clinitest

HFI vs DFI vs EFI

aldolaseA: G-neogenes (GA3P+DHAP=F1,6-biP): severe aldolase A vs B defhypoglycaemia; vs B in F+Fkinase=F6P, +aldB =DHAP+GA cy (then GA+3ose kinase..) kaussmaul="Produvka" to \\CO2:return pH),vomit,xx abdom pain,flu,confus-n:lethargy:obtund-n(dulled alert/consciouss),diab.coma,brain edema glycerid+3FA:further 3keton bodies:aceton,acetoacetate,b-OHbutirate(mistake:b-OH-butirate not keton{R-(C=O)-R}):1omuscle fuel,2/3brain brain-2/3 ketons,1/3 G, muscle-FA,including branched, RBC-G, immune cells & kidney-Glutamate in fasting: as muscle wasting:1o fuel, but not in starving: saved for RBC only! AcetylCoA CO-ase: AcetylCoA to MalonylCoA (very 1st step) Carnitine Acyl x-ase: AcylCoA x-port from outer to inner mitoch membr by carnitine

prolonged DKA

fat(=3-glycerids) lipolysis

starvation 1o fuel

Gluconeogenesis FA synth rate lim: FA b-oxid rate lim:

Glycogenolysis rate LiverP-rylase:cleaves a-1,4link:release G1P (stops 4G before lim: branch) Glycogenesis(synth G-gen synthase: form a-1,4 glycosidic link G(from UDP-G) to G)rate lim: gen chain Glycogen synth & Glycogenolys (hepatic or muscle)GlycogenSynthase:Glycogen:(Liver)GlycogenP-rylase

Glyconeogenesis rate lim: Glycolysis rate lim: PPP rate lim:

F1,6biPase: F1,6biP back to fructose6P PFK1(links P to 1st C vs PFK2 which link P to 2d C): fructose6P to F1,6biP (PentosePhosphPathw): G6PD: G6P to 6PG-conate "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 CarbamoylPsynthase1(2=Pyrimidin):CO2+freeNH4+2ATP=CarbamoylP

Lipolysis rate lim:

Urea cycle rate lim:

Pyrimidin metab-sm CarbamoylP-synthase2(1=Urea):CO2+ NH2- of rate lim: glutamine+2ATP=CarbamoylP Heme synthesis rate lim: ascobic ALA synthase:succinylCoA+Glycine=gamma-Aminolevulinic proline OH-lation in collagen, DOPA-to-NE(diet in pheochromacytoma) //vitA (Retinol=Opsin cofactor for epithel develop): //b-carotene depo=yellow skin \\B12: 2 functions only:MMA-to-SuccinylCoA with MMM & CH3 from B9 (Folate), then regenerate B9 a-ketoacid Ox-deCOO H+ mitoch RedOx H+ Ox-Phosph, NADP protein synth CoA (FA synth) with Thiolase (4th step in b-oxid-n) trans-Amin (ALA synth) aCOO- (odd-to-propionic-to-SuccinylCoA) 1C-to-DNA synth (gives out CH3 by B12, then regenerated by B12) CH3 from N-MethylTHF-to-MMA (2 funct-ns only: both to give CH3 to MMA and then to regenerate Folate) Proline HO (collag x-link) in cell vs lysin OH-lation w/Cu+ extracell

excess vitA short mem\\,leg sens\\,MMA// B1-Thiamine B2-Riboflavin B3-Niacin B5-Pantothenate B6-Pyridoxine B7-Biotin B9-Folate

B12-Cobalamin

C-Ascorbate

A-Retinol D-CholeCa+ferol E-Tocoferol K-'Koagul-r'

Opsin cofactor, epithel develop Ca+ absorb antiOxidant (unsat membr fat) "Antisteril vitamin" COO-n of E in clott protein 2,7,9,10,CSZ to bind Ca+ to catch Canadian oil,low acid(1978)=LEAR=Low(1%)Erucic Acid Rapeseed oil, 61Oleic(w9),21Linoleic(w6),11Linolenic,7satur(Palm,Stear,trans ) Turnip(ka),cabbage,Brussels sprout:mustard,Rapeseed oil(sharp-tasting glucosinolates,greenish chlorophyll,erucic acid=heart damage) Ricinus seed 50%=oil(90%=ricinolein=TG with unsatur w-9 Ricinoleic FA=18C, 12-OH-9-cis-octadecenoic acid poison from Ricinus (Lat "tick") seed coat,& low concentrations throughout the plant,grain size seed part kills adult.Castor oil=same seed propanon=simpest keton=carbonyl(-C=O)between 2 C Acetone, AcAc and b-OH-butyrate=ketones=ketone bodies from carbohydrates, FA & AA Acetone, level much lower than other 2 ketone bodies. Unlike the other 2, can't back to acetyl-CoA only excreted (urine) & exhaled

canola

Brassica rapa

Castor oil

ricin

Aceton ketobodies

spontaneous deCOO-n of AcAc

1)FAD Oxid-n=double bond; 2)Hydr-n= -OH; 3)NAD-Oxid-n= =O FA b-oxid-n 4-step keton; 4)Thiolysis:thiol between C-2&C-3; every oxid-n cycle=14 cycle ATP aut-rec AApathology aut-dom lipid d-er acute interm porphyria vit for a-ketoacid oxidative deCOO PKU \\ LDL receptors: Famil HyperCholesterolEmia:early ateroscl-s, infarction AD def Porphobilinogen-deAminase

B1 TPP

vit for AA degradation Vit for Methionine synthase Vit for MMM

B6 for Aspartate-aminoX-ase

B12 for homocysteine to Met FA(including branched)-MMCoA+MMM+B12=SuccinylCoA

a-ketoglutaric acid ketone derivatives of glutaric acid de-amination of glutamate=? starvation 1o fuel muscle 1o fuel a-ketoglutarate (-ate=anion in water from -ic acid) brain-ketons, muscle-FA, RBC-Glucose fed:glucose; fast:some FA, starv:1o:FA; vit D abuse: hyperCaemia: kidney Ca-fication glycerid+3FA:further 3keton bodies:aceton,acetoacetate,b-OHbutirate(mistake:b-OH-butirate not keton{R-(C=O)-R}):1omuscle fuel,2/3brain both fasting (some for muscle) & starving(marked:1o for muscles as keton bodies) kaussmaul to \\CO2:return pH),vomit,xx abdom pain,flu,confusn:lethargy:obtundation(dulled alert/conscious-s),diab.coma,brain edema protective:a-linolenic C18:3w3=canola; notprotective:linoleic:C18:2w6=sunflower,corn (vs18:1 w9 with OH on 12=Ricinoleic=castor oil) //P-450://GGT alcohol //SER://NADH:pyruvate->lactate:lactic acidosis & \\avail pyruvate:\\G-neogenesis:fasting hypoG-emia:starving:///TG

fat(=3-glycerids) lipolysis

lipolysis

prolonged DKA

ess-l FA:cardioprotect alcoholic liver marker alcoholics lab

alcoholic //TG path starving:///TG:1,3biPGlycerate:DiHO-AcetonP:Glycerol3P://TG metab:AcCoA alcohol path & keto x2=AcetoAcetylCoA:HMGCoA:AcetAcetate:convert to b-OHbutiric(b-OHB) by extra NADH(revved SER)://keto:acidos alcohol & FA level alcohol & uric level extra AcCoA://FA synth(used only by heart) keto & lactic compete w/uric for kidney excretion: hyperURICemia

alcohol & pH MMA MMM

extra keto & lactic acids: acodosis odd propyl: MMA: succ ( if not: MMAemia+MMAuria) B12 2 functions only:CH3 to regenerate Folate & CH3 to MMAto-Propyl by MMM-MethylMalonicMutase CH3 to MMA from N-MethylTHF (with MethylMalonylCoAMutase) MMCoA to succinyl-CoA by MMM (enzyme methylmalonyl-CoA mutase) AcAc & SuccinylCoA+thioXase=AcAcCoA; +HMGsynthase=HMG; +reductase=mevalonic ...=CH

MMM

MMM

extra from TCA fate

f:Y;+OH=Hg-sic;+HgF-Y-Hg-maleylCoAoxydase(def=Alkaptonuria)=maleylAcAc;+fumarylAcAc fumarylCoA hydrolase(def=Y-emia)=fumarylAcAc:AcAc+fumaric homogentisic(from AR=def homogentisate oxidase breaks homogentisic(toxic tyrosine) tyrosine byproduct):harmful to bone/cartilage,makes urine black PKU S #1 reaction AR:\\ f-OH-ase:newborn exposure to f:///PKetone,\\tyrosine: mousy odor+projectile vomit(~congen pyloric stenosis!) S+HomoC=Cystathionine: C+a-ketoButirate

hepatic hepatit://aromAA F,Y,W://false neurotransmitters; Rx:branchencephalopathy Rx chain AA (they inhibit FYW) Met fate (-SAMSAH) SAH fate Met+ATP=SAM(S-AdenosylMet=CH3 donor); +Methyl acceptor+methylX-ase=SAH(S-AdenosylHomocisteine) +H2O=adenosine+Homocystine; +serine+cystathionine syntase=cystathionine AR: cystathionine synthase(def)+Homocysteine+Serine (has OH) ://Met & homocysteine both in plasma & urine (includes Marfan) both Met & Homocysteine// in serum, ~Marfan (//plasma homocysteine:vessel damage:AMI,stroke,ment retard //serum Met&Homocysteine(~Marfan):vessel damage:AMI,stroke,retard:Homocystinuria 3AA=glycine+glutamate+"thion"=cysteine (rate-limiting substrate with -SH)=Glutathion:restore RBC stressed by O2

Homocystinuria

Homocystinuria cystathionine synthase GSH (G-SH)

AA-SH

thiol(sulfhydryl) of Cysteine is donor of H+ in GSH(Glutathion) of RBC, recover (reduce) by NADPH of PPP ess-l: SAM:methyl donor:SAH:homocystein:+Cysteine+Cystathionine synthase=cystathionine as GluGlyCyst vs HomoSer; GSH restore R-O-O-R in RBC,diSulf bond restored by G6PD:NADPH; Cystath=Homocyst+Ser:Homo clearance +Adenosine=SAM,donate -CH3(with Ascorbic)=Homocystine, +Serine=Cystathionine to clear from blood Met+ATP=SAM -SAH -homocyst; +Ser=cystathionine+c.lyasa =cysteine+a-ketobutyric: propionylCoA: methylmalonylCoA: succinylCoA:TCA

Met

Glutathione vs Cystathionine

Met fate

Met fate

ATP+Met+met.adenosyl-Xase=SAM; +SAM-dep SAM cycle (back to Metylase=SAH; +5CH3THF=Met; or SAM) +hydrolase=Adenosine+Homocys, +Serine=Cystathionine 1)FAD Oxid-n=double bond; 2)Hydr-n= -OH; 3)NAD-OxidFA 4-step b-Oxid-n n=(=O)keton; 4)Thiolysis: thiol inserts between C-2&C-3; =5ATP & ATP# yield (NADH=3ATP, FADH=2) too long FA oxid-n too long for mitoch FA oxid-n in peroxisomes till octanyl CoA G-Sorbitol-F Gal-Galactitol G6Pase G +aldose reductase+NADPH=S; +sorbitolDH+NAD-=F Gal+aldose reductase+NADPH=Galactitol Glyconeogenesis:liver,kidney,intestine epithelium, absence=vonGuerke's 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)

shuttles

fasting: muscle/liver: Glucagon/E: adenylate cyclase: cAMP: signals chain for Gprotein-kinaseA:P-ase kinase:G-genP-rylaseA (& \\Glycogengenolys to start Synthase) G-genolysis @ G-genP-rylaseA fasting: rate-limiting G-genesis (fed) G+G-kinase=G6P;+PGmutase=G1P;+UDP-Grylase=UDP-G(+UDP+PPi);+G-gen synthase(rate-lim,insulin-

enhanced):a1,4 link G-syl 4:6 X-ase X-fer 5-8 G from non-reducing linear end to branch point as a1,6 link postprandial="fed"://G:insulin//:hepatocyte//G-gen synth:granule w/both enzymes P-rylase&synth &membr G-genin(Tyr-to-G reducing end)

G to G-gen

60K dendrimer G-gen a1,4&a1,6=12:1 in hepatocyte granule G to G-gen & back (8% of liver weight, 1% of muscle)starts degrn 4h after meal, to G depletes in 12h 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 PC-PEPC-F1,6biPase(rate lim)-G6Pase(vonGierke)

Glucogenin

Gluconeogenesis enzymes

galactose to G=G- lactose+lactase=G+Gal;+galactokinase+Gal1P;+GALT+UDPneogenes G=UDP-Gal+G1P;+PG-mutase=G6P;+G6P-ase=G iHMG-CoA reductase(rate-limiting step in cholesterol synth:AcAcCoA:Mevalonic:Cholesterol):sole major cholesterollowering drugs

statins

A1:cleaves SN-1 acyl; A2:cleaves SN-2 acyl; B-both SN-1/SN-2; major 4 classes of C:before P=DAG+P-head; C:signal X-ductor (2nd mess-r P-lipases Inositol3P) Phospholipase D HGPRT GALT f-OH-ase homogentisic acid oxidase fumarylAcAc hydrolase hepatic F-kinase Aldolase B Phospholipase D - cleaves after P=phosphatidic+alcohol //uric:gout,retard,selfmutil-n:Lesch-Hyhan accum Gal://galactitol(//osmos:damaged lense,CNS):Galactosemia accum fenylKetone,\\Y:PKU not oxidized homogentisic=toxic tyrosine byproduct:harmful to bone/cartilage,urine black:Alcaptonuria(=ochronosis) AR://Y:cabbage odor,cirhosis to hepatocellular carcinoma: hereditory Y-osis mild Essential F-uria //F takes all P:\\ATP:weak RBC:hemolysis,//AMP:gout:hered-ry

F intolerance Ascites in alcoholosm //hydrostat P in Splanchnic capillares

bilirubin //: uncon-& \\GlucuronylX-ase(massive RBC destruct-n): // unconjugated; conjugated common bile block: // conjug; hepatocyte damage: // both any reactions=3 substances 3 reactions Substrate+Enzyme=Product metabolism=anabolism & catabolism, mutation Isol,Val,Thre,Met,Thymine,Uracil,Cholesterol,odd-chainFA: propionyl-CoA: Methylmalonyl-CoA; +Methylmalonyl-CoA mutase=MMA

MMA comes from

AcAc:.....CH HMG-CoA reductase HMG-CoA lyase branch-chain AA metab,d-se branch-chain AA: V,L,I degrad-n maple syrup urine disease

extra from TCA:AcAc & SuccinylCoA+thioXase=AcAcCoA; +HMG-synthase=HMG; +reductase=mevalonic ...=CH 3-hydroxy-3-methyl-glutaryl-CoA reductase,8-transmembrane domain anchored in membrane of ER (endoplasmic reticulum) Cholesterol-HMG-AcAc-23ATP Dehydrogenase: in muscle only, deficit:Maple Syrup urine d-se 3 essen-l: Val, Leu, Iso; degrades NOT in liver but muscle by branched-chain AA-DH-ase (if not:Maple syrup) V,L,I:branched-chain -keto acid dehydrogenase complex of 5:Thiamin,FAD,NAD,CoA,Lipoate (same as PyruvDH,a-ketoGDH) vit B3=nicotinic acid=pyridine(heterocycle:benzene,1C substit by N)-3(=3d place from N)-carboxylic acid; precursor for NADH,NADP,NADPH

Niacin

Niacin vs identical as Vit B3:prevents pellagra; but niacin=conversion nicotinamide, norm side-effects:flushing,\\cholesterol; nicotinamide:>3g/day liverg/day,extra? toxic; pandemic def-cy d- 4Vit def-cies: ABCD: A-retinol, B1=thiamin (beriberi), B3=niacin se (pellagra), vit C (scurvy), vit D (rickets), 2 forms of B3 vit B3 Niacin=pyridine(benzene w/1N hetero-ring) +COOH @3d-

pos-n from N; if +NH2 on COO=carboxamide group CONH2=nicotinamide child's fear of procedure & pain autistic Mobius pain \\ by diversion (parents presence // reaction by displaying concern) infant don't visually track pediatrician congenital facial diplegia+ocular palsy+clubfoot+syndactily+mentally retarded

reactive attachment severe parent-child bond interruption(foster home or immature dr of inf-cy parents):malnutrition:die Rett autism infant Colic precipitous development deterioration after 6mo norm development avoid human contact cry >3h/d >3d, Rx:hold,\\stimul-n,*spasmodic West:prot in mix, SW:prot-radiolabl DNA, S:DNA-DNA epidem, N:RNA-radiolabl DNA (as letter U on map)

blots ("U4")

CVS vs CVP

(Chorionic Villus Sampling)16-18 wk amniotic fluid cells>FISH,other vs Centr Vein Pressure (fluoresc in situ hybridization)DNA probe labeled w/fluoresc, uneuploidy, delition,structur abnormalities shy Autistic: hand bite/flap, Hyperactivity, \\attention, LanguageDelay, Perseveration (action/word repetition), \\eye contact vision\\, long face,ears&testicles,Flat feet,High palate, Hyperextensible joints, \\ muscle tone Restriction fragment lenth polymorphism; restr endonuclease recognize unique RFLPs pattern on DNA near centromere "AT-gene": Ataxia+Telangiectasia Testes Determ Factor=protein coded on SRY gene of Y chromosome; unfluenses gametes to develop into Testes (if TDF deficient:stay as ovaries) Duchenne,Lesch-Nyhan,Wiscott-Aldrich, HemophA,B,G6PDHdef, chr granulomatos,aGglobEmia,

FISH

Fragile X: Behavioral:

Fragile X: Physical:

RFLP Savitski gene

TDF

X-link: 10 Recessive +2

Domin Wiscott-Aldrich ?meios comb-ns from?possible

colorBlind,DI,Fragile X (Hunter,Fabry:domin) 1 of 10 X-link recessive: immunodeficiency+thrombocytopenia+eczema 2 from 4

n2=46chrsynth:(23chrom mom x2 chromatides w/1centromere=46chrsom(23mom+23dad tides)+23chrom dad:synth=46chr-tides,Total:n=4,chr) somes46,chr-des92 C1 estherase recurr colit atacks+laringoedema=AutDom Heredit Angioedema inhibitor def-cy clinic 1 c-mere for 2 sister chromatides: 46chsom(23m+23dad):meios1:each chr:2sist chr-tid(duad),2 homol duads=tetrad:recomb:align equator plate:pulled,cytokines,meios2: 2 c-meres(1 for each sister chromatid)=2 sep-ted chrtides(monades)pulled:4 cells 1n=23chr-id=23chr-somes each with 2 Allele comb-ns from 4 possible each sister cromatid got own centromere (in meo1 only 1 centrom for 2 sist,meo2 each sis get centomere but after alleles separ-d) cetromere not dubbed:duad:synapse in tetrad:crossover,pulled in 2 duads(mei2:pulled in 2monads) vs mit:each cr-id gets centromere 5:Cri-Du-Chat, 11:Wilms'(UTI tumor) 15:Angelman(mom)/Prader(dad), 22:DiGeorge (=Thymus aplasia:\\T-cell,hypoprathyroid: \\PTH) chromosom 22 deletion: Thymus aplasia:\\T-cell,hypoprathyroid: \\PTH Reciprocal(between non-homolog in meiosis 1) vs Robertsonian (long-to-long with smalls lost) Testes Determ Factor on Y: gametes become testis; w/out: stay as ovaries SRY is gene for TDF; Sex-determining Region on Y encodes TDF (protein binding in gametes to DNA for Xscription: ovaries Xform in testes)

meiosis 1

meiosis 2

mitosis

Meiosis vs mitosi

5 deletions

DiGeorge

2 translocations

TDF on ovaries

SRY vs TDF

SRY vs TDF

SRY=intronless gene encodes Xcript-n factor=DNA-binding protein=Testis Determining Factor=TDF=SRY protein, initiates male sex determ-n 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 male phenotype (look) but female genotype (XX):SRY in 1 or both X. These males are infertile females with an XXY or XY genotype, but defective (=mutated) or no SRY on Y

SRY vs TDF Mutations SRY-to-X chrom-l X-location muted SRY on Y

Int'l Olympic Com-tee 1992:"No SRY female allowed". Summer gender verification Olympics1996:detected ruled FP & were not disqualified. 2000:no screen AIS why men more Parkinson/Schizo deletions WAGR extra 21 chromos probability androgen insensitivity sdr: XY+SRY+female phenotype SRY makes a protein controling concentrations of dopamine 3=codon deletion(3extra:codon expansion),not 3:frame shift,large :Exon skip, wrong read:missense 11th chromosome:Wilm,Aniridia,Genital\\,retard mom age 20-24=1/1562; at 35-39=1/214, above 45=1/19

polydactyly,cleft lip/palate,Rocker feet,dye 1st year; retard survived 3-somias: ment&growth,low ears,micrognatia,Rocker feet,dye 1st year; 13,18,21; Down:retard,short more boy, retard, large testis; Turner:short+ovary dysgenes; Fragile X, 45,X(XO); Klinefelter:tall,small penis(hypogonadism),testicular 47XXY(XYY) atrophy,eunuchoid,may retard mut-ns: point vs frameshift 3 point: silent,missense(HbS),nonsense(Thalas) vs frameshift:3deletion(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

DNA1 vs mRNA

DNA1="sence"=non-transcribed, same nucleic bases sequense, but T bases in DNA are substituted with U bases in RNA (5'end) Cap--5'UTR(intron)--start--CDS(Coding Sequense)-Stop--3'UTR(intron)--PolyA tail (3'-end) CoDing Sequence "5 prime untranslated region"="leader sequence"=section of mRNA & DNA intron located in the 5' prime UTR

human mRNA parts CDS 5' UTR 5' UTR intron

platelet membrane Peicosanoid derivate lipid:PLA2(Cortisol!):ARA:COX(Aspirin!):endoperoxide:TXAsynt full path hase:6-ring TXA2(Thromboxane): bind rec-r:G-protein Clopidogrel vs Ticlopidin skin denudation after infect-n honey crust on eroded pustula patchy hyper & hypopigment-n both stop platelet receptors: ADP receptor modificator \\ATS vs gp IIb,IIIa (Fibrin r-r) binder (life-thretening bleed:only if Aspirin intolerance) staph:toxin:Scalded Skin S-m(exfoliation) a-hemolytic Str or Staph:Impetigo on skin, if+RBC cast=RPGN, if+hemoptys=Goodposture Melasma (pregnant face) & Vitiligo (autoimmune,trigger NOT sun, but stress)

expanding erythem Tinea Corporis (fungal "RingWorm") circul border rash DM type 1 DM type 2 embrio cell ## changes any change of skin affecting color, appearance, texture; itch,warm,bumpy,dry,cracked,blistered,swell,painful 1.Juvenile:\\production:death from DKA(KetoAcidosis): 2.Adult:\\GLUT:hyperOsmolar coma(//sugar):death from AMI(#1) 1=zigota,2=blastomere,16=morula(cleavege,no growth),128(epiblast=inner mass,trophob=outer)=blastula,3layer(ekt,mes,end)=gastrula

Gastrula: 3-layer embrio cell ecto(skin,neuro,pigment),meso(muscle,connective,includes blood),endo(alveoli,Thiroid & pancr) germ cell origin mesoderma edge in 3-layered Gastrula

gametes vs gonades 4 basic tissues types give all

germ cell w/haploid n=1(ova=egg cell & spermatazoa); vs organ (testes & ovaries) making gametes muscle, nervous, connectiv, epithelial. Any tissue will be subtype of these 4 types (blood cells=connective tissue, since originate in bone marrow) lining of glands, bowel, skin and some organs like the liver, lung, kidney lining of blood and lymphatic vessels lining of pleural and pericardial spaces cells filling the spaces between the organs, including fat, muscle, bone, cartilage, and tendon cells red and white blood cells, including those found in lymph nodes and spleen any of the conducting cells of the nervous system reproductive cells (spermatozoa in men, oocytes in women) endocrine secr-n+selective exchange of soluble blood substances through an apposition of uterine & trophoblast vascular cells able to turn into one or several of the above types always asymmetric:"animal pole"(future 2 of 3 primitive tissue types: ectoderm+mesoderm) +"vegetal pole" (future endoderm)

Epithelium Endothelium Mesothelium Mesenchyme

Blood cells Neurons Germ cells

Placenta

Stem cells egg cell asymmetry

1st protective 1st=contacting egg membr=vitelline membrane=zona envelope covering pellucida=glycoprotein egg qwerty all 3 lines strabismus QWER ty UIOP ASDF g HJKL ZXC v BNM asymmetrical eye alignment initial in kid, years later latent in nerve cell bodies/ganglion;immun\\:axonal spread:dermatomal rush 2-4w, residual postherpetic neuralgia mo-years Persistent Truncus arteriosus: congen heart d-se @ birth: truncus arteriosus never divides into Pulm a. & aorta by neural crest (50%:22q11 del-n)

VZV

PTA

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 in septum primum: for.secundum, in septum secundum: heart for.ovale Teratology study of abnormalities of physiological development 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 divides: epi(further into ecto-,meso,endo=entoderm)+hypoblasts

Birth defects %

inner mass fate

kids 3 age divisions infancy - toddler (learns to walk=12-18mo) - childhood placenta disfunction or other: general-d damage to maternal endothelium,kidney(protein in urine),liver: 2ry // vasopressive frs: //BP=PIH pregnancy-induced hypertension as result of Preeclampsia (placenta disfunction:general-d damage to mom's endothelium,kidney,liver) birth (labour,parturition) starts from contractions: sudden, with water break, or gradual // of uterus contraction (long muscle) contractions, path(cervix fully dilated, desire to push), afterbirth (placenta expelling); total:13h 1st-timers("primiparae") & 8h 2nd birth amniotic sac(amnion+chorion) rapture

Preeclampsia

PIH

partus onset

partus stages

water breaking

latent:cervix effeces 3cm;active labour:freq 3-4/10min(1min contractions phases contr+2min rest);transition:dilation 8-10cm,freq1 in 2min,7090sec each emotional phases of transition is most intense(but short): exited-focused-"self-doubt transition bouts"(giving up) indic-n for induct-n: 42w w/out labour(contraction); Apgar induction indication =assesement score (HR,resp,m.tone,skin color,response on & Apgar 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,

transverse(arm 1st) posterior baby posface fwd n 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 3 stages(divid 2phases):Period=d1, Ovulation=d14("mittelschmerz" if pain), Premens d28(glandular degeneration)

menstr cycle 3 stages

7div-ns in 7days from ovul-n~128 (2power7)=cell implant-n day & cell blastocyst(inner mass,trophoblast,blastocele=cyst) burry during # 24h, d11:maternal circul days # for implantblastocyst: 7-8-11 burry-circulation FSH:testes/ovary func-n;LH:Progesteron;hCG keep FSH,LH,hCG,Prolac LH;PL(Prolactin):menstr,lact-n; Oxitocin:contract breast(milking) tin,Oxitocin & Uterus(orgasm) hypophis://FSH(//testes:sperm; follic:ova) & hypothalam:GnRH:/ LH(theca:Estradiol,Leidig:desmolase:Ch-ol-to/? pregnenolon...:testosteron both regulate mens: Inhibin//FSH: //Inhibin: \\FSH; 2 Inhibins: Atype peaks @mid-luteal; B:2 types: peak @mid-follic & ovul-n; Activin=*Inhibin 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 Ch-ol:ovaries'theca interna:androstenedione:cross basal memb to granulosa cell:testosterone+arom-ase=Estradiol(2 -OH A,D ring,strong) liver,adren,breast: androstenedione+aromatase: estrone (ketone=O on D-ring,weak) FSH+LH:1o:ovaries' theca interna:follicle+corp.luteum+placenta:estradiol;2o:liver,adren,bre ast:estrone(>estradiol postmenop)

Inhibin vs Activin

Estrogen

estrogen 1o synth mech-m estrogen 2o synth mech-m

Estrogen path

Estrogen for women women:2ry sex characteristics; men:brain mascul-n,sperm vs men matur-n, libido oral contraceptives Estrogen \\ circulating FSH & LH Estrogen loss breast cancer hormonal Rx hormonal Rx vs horm-replacem Leydig interstitial cell Leydig interstitial cell bone minerals\\,45%alveoli\\,cholesterol//:cardiovasc d-ers 80% breast cancer need estrogen to//("hormonreceptor+","hormon sens-ve"):Rx:estrogen suppression hormonal=anty-estrogen; replacement=estrogen 0.3-0.6-1.2mg (Premarin+Provera="PremPro"),topical avoid liver 1st pass:\\clotting small eosinophilic (from //SER) cells adjacent to outsid of seminiferous tubules: testosteron \\ LH pituit:FSH://Leyd.membraneLHreceptors;FSH:activatesLeyd.cholesterol desmolase:cholest-l to pregnenolone(testosterone synth) fetal Chorion Frondosum (vs non-placental but surrounding fetus avascular Smooth Chorion)+maternal Decidua Basalis(vs Capsularis around fetus)

placenta 2 parts

shallow placent:inflam:vasoactiv:PIH(pregnancypreeclampsia 20wk inducedHT)+signif-nt(>300mg/d)urine protein (no protein=Gestational HT)both=emergency shallow placent:inflam:vasoactiv:PIH(pregnancyinducedHT)+signif-nt(>300mg/d)urine protein (no protein=Gestational HT)both=emergency

PIH vs GHT

med eminence+ant.lobe(post=neuro:ADH,Oxytocin) no arter, postpartum pituitary only Long Portal veins between Sup(1o) & Inf(2ry) hypophyseal ishemia plexi 1)ant:basophil(GnTH=FSH+LH,Thyrotr:TSH,Corticotr=ACTH),ac pituit cells by lobes idophil(Somatotr=GH,Mammotr=PL); 2)post:Oxytocine,ADH=Vasopressin pituit cells of intermed lobe milk synth vs milking hormons chromaphob(stem,degranulated,supporting=folliculostellate) 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

hormons Oo- & spermatogenesis start 2 principal gonadotropins Sperm cell mitos

by PIH=DOPA oogenesis:meiosis starts before birth,arrest at prophase1 till puberty; spermatogenesis:starts only at puberty LH,FSH (2peptide chains: nearly identical alpha chain & specific beta w/disulfide bonds) & 3d placental hCG Spermatogonia(primitive germ):repeated mitos to Prime spermatocyte 1ry spermatocyte:DNAReplic-n:1st divis-n(Meios=Reducn):paired homolog(NOTsister)chromatides:Transpositn=crossover(Meios1Prophase) 2ry spermatocyte:2d meiot div-n=4 small spermatides w/haploid chromosome# seminiferous tubules:spermiogenes(maturn):spermatozoa

Sperm cell w/crossover

Sperm cell w/haploid

Estrogen peak before Ovul-n:+feedback to Menses cycle peaks hypothGnRH(pulsatile)://hypophLH:Ovul-n,(FH peaks too);Progesteron(//secret)peaks before mens 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)

3 Estrogens

estrous:endometrium reabsorb endometrium (if no concept-n), Menses & Estrous menst-shed it:Greate Ape only:includes cycles human,chimpanzee,gorilla,orangutan)