| Question |
Answer |
| Essential amino acids |
Phe, Val, Trp, Thr, Iso, Met, His, Arg, Lys, Leu |
| What is interesting about arg |
can be synthesized in body, but not enough can |
| BV |
biological value |
| Products of AA |
body protein, gluconeogenesis, glycogen, ketone bodies, FA, steroids, porphyrins, creatine, neurotransmitters, purines, pyrimidines |
| Positive N balance |
N consumed>N excreted |
| Negative N balance |
Nconsumed
|
| When is there a positive N balance |
growth, pregnancy, lactation, recovery from emaciating illness |
| When is there a negative N balance |
trauma, burns, illness (cancer), post-surgery, starvation, kwashiorkor, lack of essential AA in diet |
| What lives longer, regulatory or structural proteins |
regulatory |
| How many g/day of protein do we eat |
70-100g |
| How many g/day of protein is from sloughed off intestinal cells |
35-200g |
| 3 phases of digestion |
gastric, pancreatic, and intestinal |
| gastric phase |
pepsin breaks down protein into small polypeptides; HCl denatures protein |
| pancreatic phase |
HCO3-, trypsin, chymotrypsin, elastase, caboxypeptidase A and B break polypeptides into AA and oligopeptides |
| intestinal phase |
digestive enzymes (Aminopeptidase, dipeptidase, and tripeptidase) from intestinal epithelial cells break oligopeptides into AA’s |
| 3 hormones that control protein digestion |
Gastrin, Cholecystokinin, and Secretin |
| Gastrin |
stimulates HCl secreation, serous cells secrete pepsinogen which is converted to pepsin in low pH |
| CCK |
stimulates gall bladder to release bile, stimulates release of degradative enzymes (zymogens) and the release of enteropeptidase which converts trypsinogen to trypsin |
| Secretin |
stimulates HCO3- release into intestine |
| Why have multiple enzymes with various specificities |
tightly regulated, efficient, and step-wise progression ensures safety and accuracy |
| Where does pepsin cleave |
Phe, Tyr, Glu, Asp |
| Where does trypsin cleave |
basic AA (Arg, Lys) |
| Where does chymotrypsin cleave |
aromatic AA (Phe, Tyr, Trp, Leu) |
| Where does elastase cleave |
small side chain AA (Ala, Gly, Ser) |
| Name the zymogens |
pepsinogen, trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase |
| How to prevent self-destruction of body proteins |
zymogens; quick turnover; trypsin inhibitor in pancreas controls enzyme activity |
| How do AA get into intestinal epithelial cells |
Na+ AA symport translocation system |
| How many brush border AA transport systems are there and where are they |
at least 7; in the intestinal and kidney epithelial cells |
| Cystinuria |
defective lys/arg/cys-cys/ornithine transporter; clinically important in kidney, not intestine; excretion of cysine and basic AA in urine; kidney stones; drink lots of water |
| Neutral amino aciduria |
hartnup disease; failure of renal/intestinal cells to absorb neutral AA; neutral AA in urine; pellagra-like rash, headache, psychiatric symptoms (reduced trp for niacin) |
| Where are AA converted to NH4+ |
liver |
| 3 steps of AA conversion to NH4+ |
1)Transamination 2)oxidative deamination 3)urea cylce |
| transamination step |
alpha AA + alpha ketoglutarate ->alpha keto acid + glutamate |
| oxidative deamination step |
glutamate + NAD + H2O ->alpha keto glutarate + NADH + NH4+ |
| glutamate to aspartate conversion |
glutamate + pyridoxal phosphate ->alpha ketoglutarate + pyridoxamine phosphate; pyridoxamine phosphate + oxaloacetate ->aspartate |
| PLP |
pyridoxal phosphate; a derivative of vit B6; linked to lys of aminotransferase and helps move amino group |
| Are transaminations irreversible |
no, they are reversible |
| How do you monitor liver cell damage caused by liver diseases |
monitor levels of plasma aminotransferases |
| hyperammonemia |
hyperammonemia-(impaired N excretion); reversal of glutamate; coma, brain damage, death |
| oxidative deamination rxn; depletes alpha ketoglutarate, ATP, NAD(P)H; glutamate=neurotransmitter; replace AA with alpha keto acids |
|
| Which AAs cannot participate in transamination rxs |
Thr, Lys, Pro |
| Where does oxidative deaminaton of glutamate occur |
mitochondria of liver (and kidney) |
| Regulation of oxidative deamination of glutamate |
-GTP/ATP, +GDP/ADP |
| Sum of urea cycle rxn |
Asp + NH4 + CO2 + 3ATP -> urea + fumurate + 2ADP + AMP + 2Pi + PPi + 3H2O; 4 ATP equivalent consumed; CO2 provides urea carbon; urea N’s come from free ammonia and aspartate |
| Regulation of urea cycle |
amount of enzymes and CPS I activity (more protein leads to more enzymes) |
| CPS I regulation |
absolute requirement for N-acetylglutamate whose production is activated by Arginine |
| What links the urea cycle and the TCA cycle |
fumurate |
| Hyperammonemia IA |
N-acetylglutamate synthase deficiency; autosomal recessive |
| Hyperammonemia I |
CPS I deficiency |
| Hyperammonemia II |
Ornithine Transcarbamoylase deficiency; X-linked |
| Where does N accumulate in hyperammonemia |
glycine and glutamine |
| Citrullinemia |
arginosuccinate synthase deficiency; citrulline can be excreted |
| Arginosuccinic aciduria |
arginosuccinate lyase (arginosuccinase) deficiency; arginosuccinate can be excreted |
| Argininemia |
arginase deficiency; arg excreted; rare; developmental abnormalities |
| General treatment regimens for urea cycle enzyme deficiencies |
low protein diet with keto acid supplement, arginine supplementation, benzoate/phenylacetate supplementation |
| Alternative nitrogen excretion route |
benzoate and phenylacetate |
| 6 sources of ammonia |
1)transamination/oxidative deamination of AA 2)glutamine -> glutamate 3)bacterial urease 4)other AA 5)amine oxidase 6)purine/pyrimidine metabolism |
| where does hydrolysis of glutamine to glutamate occur |
liver mitochondria, intestine, and kidney (to regulate pH) |
| where does bacterial urease act and what medical condition is linked to it |
intestine (urea is hydrolyzed to ammonia); important in renal failure |
| other than glutamine, what AA’s directly produce ammonia |
Asparagine (asparaginase), Serine/Threonine (dehydratase), Histidine (histidase), glycine (glycine cleavage complex) |
| how are ammonia and glutamate produced in extrahepatic tissues transported into the bloodstream and liver |
in the form of glutamine (liver, muscle, brain) and alanine (muscle to liver; convert to/from pyruvat) |
| ketogenic AAs |
leucine and lysine |
| both glucogenic and ketogenic AAs |
threonine, isoleucine, phenylalanine, tyrosine, tryptophan |
| 7 common products from AA carbon skeleton |
pyruvate, oxaloacetate, fumarate, succinyl CoA, alpha-ketoglutarate, acetyl CoA, acetoacetyl CoA |
| 2 common types of AA degradation rxns and what they require |
transaminations (PLP) and one-carbon transfer (biotin, B12, tetrahydrofolate, and/or SAM) |
| C3 family of AA and what they convert to |
Ala, Ser, Cys all go to pyruvate; Trp->Ala; Gly->Ser; Thr->Gly or Thr->Acetyl CoA or Thr->Propionyl CoA->Succinyl CoA |
| Fates of Gly and their cofactors |
either Serine (tetrahydrofolate) or CO2 + NH4+ (tetrahydrofolate) |
| Nonketotic hyperglycinemia |
defect in glycine cleavage, increased glycine in blood; mental retardation, death in infancy; glycine is an inhibitory neurotransmitter |
| C4 AA family |
Asparagine->Aspartate->Oxaloacetate or Aspartate->Urea Cycle |
| Asparaginase in cancer therapy |
normal cells but not cancer cells can synthesize asparagine; so, give asparaginase to change blood-born Asn to aspartate and cancer cells don’t have Asn |
| C5 AAs |
can convert to Glucose; Arg, His, Gln, Pro, Glu |
| C5 pathways |
Arg->Ornithine->Glutamate Semialdehyde->Glutamate->alpha ketoglutarate; proline->glutamate semialdehyde; histidine->FIGLU->Glutamate (FH4); Glutamine->Glutamate |
| Branched chain AAs |
Val, Leu, Ile |
| Where does branched chain AA catabolism occur |
muscle primarily |
| Branched chain AA catabolism pathway |
val/iso/leu-transamination(PLP)>branched chain alpha-keto-acid-oxidative decarboxylation(thiamine)>intermediate->succinyl CoA for val/iso or Acetyl CoA for Iso/Leu |
| Maple syrup urine disease |
defective branched chain alpha keto acid dehydrogenase; lots of branched chain AA and alphaKA in blood and urine; mental/physical retardation; short life-span; treat with diet low in branched AA or thiamine |
| Methionine catabolism |
met->SAM->S-adenosylhomocystein->L-homocystein [serine adds here]->cystathionine->cysteine + alpha-ketobutyrate + NH4 |
| Homocystein’s two fates |
cystein and methionine (50-80% of homocystein goes this route; it is methylated with vit B12 as a cofactor) |
| Why is SAM important |
it can methylate lots of stuff to deactivate them (DNA, proteins, etc.) |
| Where does the C, N, CH3, and S of methionine end up |
C-propionyl CoA; N->NH4; CH3->acceptors; S->Cys |
| Homocystinuria (=hyperhomocystinuria) |
deficiency of the homocys->methionine pathway or in the homocystein->cystein pathway;neurotube, mental, heart, lens problems; restrict met diet |
| AA that lead to propionyl CoA |
Thr, Met, Val, Ile |
| Propionyl CoA to Succinyl CoA requires what cofactor |
biotin and vitamin B12 |
| 2 rxns and 1 fxn that require vitamin B12 |
homocystein->methionine; methylmalonyl CoA->Succinyl CoA; regeneration of tetrahydrofolate |
| Phe/Tyr catabolism and the diseases if enzyme is missing |
Phe-PKU>Tyr-Tyrosinemia II>p-hydroxyphenylpyruvate->homogentisate-alcaptonuria>->-tyrosinemia I> Fumurate + Acetoacetate |
| Phenylalanine hydroxylase (Phe->Tyr) needs what |
BH4, O2, NADH |
| PKU |
phenylketonuria-deficiency of phenylalanine hydroxylase or H4; accumulation of Phe or phenylketones, 20X increase in Phe in blood; 1% of institutional patients, 1.5% of population; low Phe diet (Tyr becomes essential) |
| Alcaptonuria |
absence of homogentisate oxidase; black urine (homogentisate); mostly benign |
| What cofactor transfers CO2 |
biotin |
| What one carbon units can tetrahydrofolate transfer |
CH, CHO, CHNH, CH2, and CH3 |
| What cofactor transfers CH3 |
Tetrahydrofolate, B12, and SAM |
| One carbon pool |
all three of these can interconvert via met metabolism; SAM-(CH3), B12-CH3, THF-C |
| Sources of one-carbon units for THF |
serine, glycine, histidine, formaldehyde, formate |
| Recipients of carbon for THF |
dTMP, Serine, Purines, B12-CH3 |
| THF from folate synthesis |
folate (dihydrofolate reductase) dihydrofolate (dihydrofolate reductase) tetrahydrofolate |
| Remedy for deficiency of dihydrofolate reductase |
treat with 5-formyl THF |
| Consequences of no THF |
metabolism of certain AA defective; no purines in dTMP; no homocys-Met |
| Consequences of no B12-CH3 |
no homocys-Met; no THF regenseration |
| Methyl-folate trap |
the rxn that creates methyl tetrahydrofolate is non reversible and guarentees methyl-FH4 to go to THF (B12 is needed); this ensures methylation for nerves, brain, and not for purine/pyrimidine synthesis when methyl groups are scarce |
| Effect of THF metabolism on AA metabolism |
glycine cleavage and homocys->Met conversion (SAM production; B12 required) |
| Effect of AA metabolism and B12 on THF metabolism |
methyl-folate trap |
| 5 ways to produce homocystinuria |
1)defect in cystathionine formation 2)defect in B6 metabolism (cystathionine synthase uses it as a cofactor) 3)defect in homocys methyltransferase (or methionine synthase) 4)defect in B12 metabolism 5)defect in folate metabolism |
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