Liver: mitochondria, then cytosol
Urea cycle
Two nitrogens in, one urea out.
Costs 3 ATP (4 high-energy bonds) per urea
This mnemonic, unpacked word by word →
The two nitrogens come from different places: one from free ammonia via carbamoyl phosphate, one from aspartate. The fumarate released links straight into the TCA cycle.
1
NH₃ + CO₂
Carbamoyl phosphate
Carbamoyl phosphate synthetase Irate-limiting 2 ATP
“Careless” → Carbamoyl phosphate
Rate-limiting. Activated by N-acetylglutamate. Do not confuse with CPS-II, which is cytosolic and belongs to pyrimidine synthesis.
2
Carbamoyl phosphate + Ornithine
Citrulline
Ornithine transcarbamoylase
“Crappers” → Citrulline
Deficiency is the most common urea cycle disorder: hyperammonemia with orotic aciduria.
3
Citrulline + Aspartate
Argininosuccinate
Argininosuccinate synthetase ATP
“Also” → Argininosuccinate
Aspartate donates the second nitrogen of urea.
4
Argininosuccinate
Arginine + Fumarate
Argininosuccinate lyase
“Frivolous / About” → Arginine + Fumarate
The fumarate joins the TCA cycle, the link that makes this the "Krebs bicycle".
5
Arginine
Urea + Ornithine
Arginase
“Urination” → Urea + Ornithine
Ornithine returns to the mitochondrion and the cycle repeats.