1-15 Nitrogen Metabolism Flashcards
(34 cards)
role of glutamate in urea production
glutamate collects nitrogen from other AAs AA + a-ketoglutarate via TRANSAMINATION -> a-ketoacids + glutamate glutamate via GLUTAMATE DEHYDROGENASE -> NH4+ OR glutamate + OAA via TRANSAMINATION -> a-ketoglutarate + Aspartate NH4+ and aspartate feed into urea cycle = UREA :)
Transamination reaction
AA1 + alpha-ketoacid2 via TRANSAMINASE -> alpha-ketoacid1 + AA2 Aspartate + aketoglutarte -> OAA + glutamate AA that cannot do this: lys, thr, pro, HO-pro Requries vitamin B6 coenzyme (pyridoxal phosphate) to transfer Nitrogen
alanine aminotransferase rxn
glutamate + pyruvate via ALANINE AMINOTRANSFERASE -> alanine + alpha-ketoglutarate
aspartate aminotransferase rxn
glutamate + OAA -> aspartate + alphaketoglutarate able to feed in to TCA (OAA, AKG)
glutamate dehydrogenase
oxidative deamination, only AA that undergos rxn like this H2O + glutamate + NAD(P)+ via GLUTAMATE DEHYDROGENASE -> NH4+ + a-ketoglutartate + H+ + NAD(P)H NAD: oxidative deamination NADP: reductive amination
glucose/alanine Nitrogen transfering cycle
Liver: glucose exported to peripheral tissues Muscle: glucose->pyruvate/lactate->alanine (via Alanine aminotransferase) alanine exported to blood to liver Liver: alanine + a-ketoglutarate via ALT -> pyruvate + glutamate; glutamate via GLUTAMATE DEHYDROGENASE -> NH3 + a-ketoglutarate; NH3 -> urea
Purine nucleotide cycle in skeletal muscle
prolonged exercise induces ATP->ADP->AMP via AMP deaminase -> NH3 (to glutamine) + IMP IMP + Aspartate -> adenylosuccinate -> fumarate + AMP, cycles
glutamine transfer cycle between liver/peripheral tissues
peripheral tissue: a-ketoglutarate + NH4+ via GLUTAMATE DEHYDROGENASE -> glutamate; + NH4+ +ATP via GLUTAMINE SYNTHASE -> ADP + glutamine Blood: glutamine Liver: glutamine via GLUTAMINASE -> NH4+ + glutamate; via GDH -> NH4+ + a-KG both of the NH4+ feed in to urea cycle
sources of nitrogen for urea cycle
muscle: aspartate / purine nucleotide cycle -> fumarate + NH4+ Gut: AAs via bacteria -> urea -> NH4+ Glutamate via Glutamate dehydrogenase -> a-KG + NH4+ Glutamine via Glutaminase ->Glutamate + NH4+ Asparagine via Asparaginase -> aspartate + NH4+ Serine via SERINE DEHYDRATASE (PLP pyridoxal phosphate) -> pyruvate + NH4+ Threonine via PLP -> a-ketobutyrate + NH4+ Histidine ->urocanate + NH4+
Urea cycle
mito: 1. CO2 + H2O -> HCO3- + NH4+; +2ATP via CARBAMOYL PHOSPHATE SYNTHETASE 1 (CPS1) -> 2ADP + 2 Pi + carbamoyl phosphate 2. carbamoyl phosphate + ornithine via ORNITHINE TRANSCARBAMOYLASE -> citrulline 3. citrulline exits mito via channel to cytosol) cytosol: 4. citrulline + aspartate +2ATP via ARGININOSUCCINATE SYNTHETASE -> 2AMP + PPi + Argininosuccinate 5. Argininosuccinate via ARGININOSUCCINATE LYASE -> Fumarate + Arginine 6. Arginine + H2O via ARGINASE -> Urea + ornithine 7. ornithine enters mito via channel to continue cycle; urea excreted in urine Summary: ammonia input from aspartate and mitochondria respiration
Regulation of CPS1
Glutamate + AcetylCoA *+regulated by Arginine) -> N-acetyl glutamate (+ allosteric regulator of CPS1) CO2 + NH4+ + 2ATP via CARBAMOYL PHOSPHATE SYNTHETASE -> 2 ADP + 2Pi + carbamoyl phosphate
Krebs bicycle
essential AAs
Lysine
Isoleucine
Leucine
Threonine
Valine
Phenylalanine
Methionine
Histidine
Need to get from diet
degredation of branched chain AAs
Valine -> propionyl Coa
Isoleucine -> Acetyl COa + Propionyl coA
Leucine -> Acetyl Coa + Acetoacetate
If can form: propinoyl = gluconeogenic
If can form acetyl coa or acetoacetate = ketogenic
common process in muscles
Serine synth/degrade
glucose—-> 3-phosphoglycerate—-> serine
serine—-> pep->pyruvate
*involves intermeditates of glycolysis and self regulates
metabolism of glycine
serine <-via SERINE HYDROXYMETHYL TRANSFERASE PLP> glycine
threonine -> glycine -> CO2 + NH4+
glycine->*oxalate (kidney stones) or a-KG–>H2O + CO2
*major way to degrade
Cysteine synth/degrade
serine + methionine —> cysteine —>NH4 to urea, carbohydrates or GAGs, sulfate in urine
degradation of phenylalanine and tyrosine
phenylalanine via PHENYLALANINE HYDROXYLASE (PKU deficient enzyme) -> tyrosine —–> Fumarate (TCA) + Acetoacetate
Synth of non-essential AAs
Non-essential AAs (formed from)
Asparagine (glutamine)
aspartate (OAA)
Glycine (Glucose/serine)
Serine (glucose)
Cysteine (Glucose/serine)
Alanine (Pyruvate)
Tyrosine (phenylalanine)
Glutamine (a-KG/glutamate)
Glutamate (a-KG)
Proline (glutamate semialdehyde)
Arginine (glutamate semialdehyde)
Sources of carbones in purines:
Pyrimidines:
purines: aspartate, glycine, glutamine amide N
glutamine amide N, aspartate
purine synthesis
PPP -> ribose 5-phosphate + ATP via PRPP SYNTHETASE -> AMP + PRPP
PRPP + glumaine ——> IMP
IMP + GTP + Asparatate -> AMP*
IMP + ATP + Glutamine -> GMP*
*reciprocally regulate each other to keep synth levels equal
AAs that make carbon skeleton: aspartate, glutamine, glycine
Ribose to deoxyribose
must be done at Dinucleotide stage! (NDP->dNDP) via RIBONUCLEOTIDE REDUCTASE
purine nucleotide cycle in muscle
important source of E during exercise
Aspartate (enters) + IMP + GTP (enters) -> GDP (exits) + P (exits) + Adenylosuccinate -> fumurate (exits to TCA) + AMP -> NH3 (exits) -> IMP
