usmle medical biochemistry
TRANSCRIPT
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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:
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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(
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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
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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
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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
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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
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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
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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
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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
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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-
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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
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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-
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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,
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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)
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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
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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,
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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)
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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
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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)