urea cycle Flashcards
where does urea cycle take place? (tissue + organelle)
- primarily in liver
- mitochondria & cytosol
what is the purpose of the urea cycle?
eliminate NH3 from the body by converting it to urea
what is the structure of urea?
NH2–C=O–NH2
where are urea’s C and N atoms derived from?
C: CO2
N: ammonia (NH3), aspartate
which enzymes of urea cycle are found in the mitochondria? (2)
- CP synthase 1
- OTC
which enzymes of urea cycle are found in the cytosol? (3)
- ASS
- ASL
- Arginase
true/false: the same transport protein carries ornithine & citrulline across inner mitochondrial membrane?
true
how is the urea cycle regulated? (4)
- Compartmentalization
- Transcriptional and Translational Control (increase enzymes to upregulate urea cycle)
- Feed-Forward Regulation
- Allosteric Control
what is the rate limiting enzyme of the urea cycle?
CP synthase 1
what is the substrate, and allosteric activator for CP synthase 1?
substrate: NH3
activator: N-acetylglutamate
how is N-acetylglutamate produced?
- Glu→ N-acetylglutamate
- allosterically controlled manner too: acetylglutamate synthase/N-acetyl-transferase (upregulated by Arg)
- increase Arg→ increase acetylglutamate synthase→ increase N-acetylglutamate→ activate CPS1→ increase carbamoyl phosphate
what is the overall equation of urea synthesis?
NH4+ + HCO3- + Aspartate→ Urea + Fumarate + H+
3ATP→ 2ADP + AMP + 2Pi + PPi
how is urea cycle and TCA cycle linked?
fumarate produced from urea cycle→ enters TCA cycle→ malate→ oxaloacetate→ re-enters urea cycle via conversion by aspartate transferase→ aspartate
what disease causes defect in carbamoyl phosphate synthethase 1 (CPS1)?
hyperammonemia 1
what disease causes defect in ornithine transcarbamoylase (OTC)?
hyperammonemia 2
what disease causes defect in argininosuccinate synthetase (ASS)?
citrullinemia
what disease causes defect in argininosuccinate lyase? (ASL)
argininosuccinic aciduria
what disease causes defect in arginase?
argininemia
how does ammonia get eliminated? (7)
assimilation (incorporated into organic compounds)
1. by glutamine synthetase (glutamate→ glutamine)
2. by glutamate dehydrogenase (a-KG→glutamate)
3. by carbamoyl phosphatate synthetase (CPS1)
excretion:
4. as NH4+ ions
5. as urea
6. as creatinine
7. as uric acid
