L9 prot and aa metab Flashcards
LO2: def glucogenic and ketogenic AA.
-glucogenic eg alanine. Ketogenic eg lysine. Both eg threonine. Deps on s/c.
-AA breakd if excess. Maj in liver. Us start rem NH2 trans/deamin.
Fate of C, conv to:
Pyruv, OAA, fumarate, aKG, succin coA- prod by the 14 glucogenic AA.
ACoa, acetoacyl coA- prod by leucine and lysine ketogenic.
Us prods oxid to H2O, CO2 and energ. Starvat/diab- used to prod gluc and ketone bods.
LO3: desc how AA are catab in bod.
-mob prot reserves. Extra stress eg Starvat. Horm contr. AV man 6kg musc prot.
Insulin and GF incr prot synth, decr deg. Glucocorticoids decr synth, incr deg. Cushings high cortisol= weak dermis=striae.
-9 seen AA- isoleucine, lysine, threonine, histidine, leucine, meth, phe, tryp, valine. Some condit Essen eg if growing or preg need Arg, tyrosine (from Phe), cys (from met). Anim vs pl ori.
AA pool=tot free AA in bod. 100g in 70kg man. Fast conc= 3mM. 50% pool= glutamine, ala, pro, gly. 75% rel dur breakd for prot synth. 25% oxid for energ or used to synth N comps.
-AA synth- non Essen. C from glycol (C3). PPP (C4+5). TCA (C4+5). Animo grp from transamin of NH3.
-AA funcs- prot synth reqs all, other N comps req specif ones. Excess conv to intermed so far carb/lip metab or oxid for energ.
Synth sig molecs- NO from L-Arg. Hydrogen sulphide from Lcys.
-synth N comps- eg tryp to 5-HT. His to histamine. Tyrosine to melanin, thyr horms, catecholamines eg adren, Na, drop. Gly to purines, GSH, porphyrins, creatine.
Fate of N atoms- rem NH2 by trans or deamin allow oxid metab of C skel. Then N to other comps to urea excret.
-transamin- (see diags)
Most a/t use aKG to funnel NH2 to glutamate. Excep asp a/t uses OAA to funnel NH2 onto asp.
All a/t req coenzyme pyridoxal phosphate- vit B6 deriv. Glut and asp can rem NH2 in paths other aa’s can’t ent. Feed to urea cyc. Cortisol stims transaminase synth in liver.
-imp a/t’s- alanine a/t (ALT)- ala and aKG to glutamate and Pyruv.
AST- OAA and glutamate to asp and aKG.
Meas in liv func. High in plasma if lot necrosis eg vir hep, autoimm liv dis, tox inj. Death cap shroom 20x.
-deamin- NH2 to free NH3. Main liv and kidn. Keto acid can prod energ. Imp in deamin diet D-AA in plant and microorg. NH3+4 v tox must rem. Conv to urea for excret in urine. At phys pH NH3 rap forms NH4+.
Sev enzs deamin- AA oxidises, glutaminase, glutamate DH.
AA oxidises- low specif. AA to keto ac and NH3. Liv lot D-AA oxidase. non func as prot synth.
Glutaminase- specif. Glutamine to glutamate and NH3.
Glutamate DH- glutamate+NAD+H2o to aKG+NH4+NADH+H+.
Imp in dispos AA and synth non Essen. Direc determ by S and P.
LO4: desc how NH3 metab in bod.
-pH7.4 mostly NH4 as reac with H2O. Tiss prod it and abs GIT. Blood 25-40uM. Detox:
Urea- 47% N, non tox. V sol. Inert in hum to end breakd to rel NH3. Most excret in urine. Osmot role in kidn tubules. HyperNH3 in liv dis.
Detec by synth N comps eg glutamine OR urea. Can be excret direc too.
Glutamine synth- NH4+glutamate+ATP to glutamine+ADP+PI via glutamine synthetase. Glutamine then to liv and kidn where conv to NH4 for excret/ urea and glutamate- by hydrol glutaminase.
-Urea cyc diag.
Liv 5 enz- amnt rel to conc NH3, not direc regul, high prot diet= incr enzs. Starvat decr. Inducib not regul. Refeed synd- maln decr enz=incr tox. RF BMI under 16, loss 15% weight in 3-6 mnth, 10d or more with little or no nutr. Need refeed 5-10kcal/kg/d. Incr grad dur 1wk.
-defec urea cyc- autos recess enz defic. 1/30000 LB. mut= part LoF, compl=die.
Causes- hyperNH3. Accum/excret of urea cyc intermeds. Clinic sev NH3 tox deps on: which enz defec, amnt prot eaten. Sev symp 1d old, untreated die. Mild defic symp early childhood.
Symps- vom, lethargy, irrit, ment retard, seiz, coma.
Managem- low prot diet. Repl AA in diet with keto ac no NH2. Keto AV conv to AA using NH4=decr conc.
HyperNH3 also secondary to liv dis eg cirrhosis- can’t rem NH3 from portal blood.
-fate of urea- diff hepatoc to blood. To kidn filt and excret. Some diff X int wall-bact breakd to NH3 then reabs. Kidn fail= incr urea= prod NH3 from it= hyperNH3.
-NH3 tox- read diff, xBBB, tox to brain. Blood lev 25-40uM. Sev tox effs:
Interf AA transp and prot synth. Disrup cereb blood flow. Incr blood pH. Interf metab of excit at aa neurot’s eg glutam/asp. Alt BBB. Interf TCA (aKG to glutamate)=decr energ brain. Blurry vis, haemorr, slurr speech, coma. May aff pH in CNS cells.
-NH3 transp 2 mechs- NH3 tiss to dispos.
Glutamine- form from NH3 and glutamate. Glutamine to liv and kidn cleaves by glutaminase to glutamate and NH4. In liv NH4 to urea cycle, kidn to urine.
Alanine- in periph tiss by transamin Pyruv. Ala to liv to Pyruv by transamin. NH2 fed via glutamate to urea cyc for dispos. Prov to gluc to tiss. (See diag).
LO5: desc clinic conseqs Phe metab defec.
-clinic probs AA metab- over 50 Inher dis. Us part loss enz activ. Under 1/250000 but is sig propor paed genet dis. Untreated= intell imp. Tx restric AA diet. In W countries screen- heel prick- SC, CF, congenital hypothyr. Inborn err aa metab eg PKU, maple syrup urine dis, isovaline audura, homocystinuria.
Only us clinic conseq when aff enz is in AA breakd as synth defec. Tx by diet. AA/prods of breakd accum=tox or metab to tox=retard/dev abn.
-PKU- most comm. 1/15000. Defic Phe hydrolase. Autos recess chrom 12. Accum Phe in tiss, plasma, urine. Phenylketones in urine. Musty smell.
Tx- low Phe diet. Avoid artif sweetener. Avoid high prot food. (See diag).
Homocystinuria
-prob breakd met. Excess homocystine (2 homocysteine linked by S-S)= Oxidised homocysteine excret in urine. Autos recess. 1/344000. Defec cystathionine beta synthase most comm. affs CT, musc, CNS, CVS. Tx low met diet, avoid dairy, meat fish, egg, nuts. Supplem cys, vitB6 and B12, betaine, folate.
(See diag)
Kids homocystinuria sim symp marfans where lack exp fibrillin 1 in CT. as fibrillin 1 struc disrup.
LO1: expl N bal and prot t/o
-Maj N cont compons- AA, prot, purine and pyrim.
Smaller amnts- porphyrins (haem), creatine, neurot eg drop, some horms eg adren, carnitine.
-creatinine clinic marker- breakd of creatine and cP in musc. Prod const rate norm dep on musc mass unless musc wasting. So excret/24hr propor to musc mass. Filt via kidn to urine. Incr if renal dam. Nephrons- glomerular filt rate.
Ref range men 14-26mg/kg. fem 11-20. 3% bod weight is N.
-N bal- N eq norm- no change tot bod prot.
Pos N bal if intake more than output=incr bod prot. Eg growth, preg, post malnutr.
Neg N bal if intake less than output= net decr bod prot. Eg trauma, infec, maln.
Norm 70kg male diet prot 16g (in 100g/d 16%). AA pool 16g N prot synth into bod prots cont 2kg N. Or makes N cont comps 60gN. Loss in eg skin, hair, nails 2g N. Excret NH3 and N waste prod in faeces and urine 14g N.
Over 90% N intake as prot. 85% leaves as urea, 5% creatinine, 3% NH3, Uric ac.
-prot t/o- all bod prots contin breakd and resynth. Norm eq. Not rand, rate deps on prot , var dur growth and aging. AV t1/2 80d. Tot t/o ad 300-400g/d. Of this 100-150g musc prot and dig enz.
(See diag). AA from diet or de novo forms cellu prot eg musc. Or to liver to form urea, ketone bods, or ent glucoeneogen.
