Cps 1 and cps2 difference
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CPS1 vs CPS2 carbamoyl phosphate synthetase differences location function
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Here is a complete comparison of CPS I vs CPS II (Carbamoyl Phosphate Synthetase I and II):
CPS I vs CPS II — Key Differences
| Feature | CPS I | CPS II |
|---|---|---|
| Pathway | Urea cycle | Pyrimidine biosynthesis (de novo) |
| Location | Mitochondrial matrix | Cytosol |
| Nitrogen source | NH₄⁺ (free ammonia) | Glutamine |
| Activator | N-acetylglutamate (NAG) | PRPP (5-phosphoribosyl-1-pyrophosphate) |
| Inhibitor | None (NAG is obligatory activator) | UTP (end-product feedback inhibition) |
| Rate-limiting? | Yes — rate-limiting step of the urea cycle | Yes — regulated step of pyrimidine synthesis |
| ATP consumed | 2 mol ATP per mol carbamoyl phosphate | 2 mol ATP per mol carbamoyl phosphate |
Details
CPS I — Urea Cycle
- Found in hepatic mitochondria; catalyzes condensation of CO₂ + NH₄⁺ + 2 ATP → carbamoyl phosphate
- Obligate allosteric activator: N-acetylglutamate (NAG), which enhances the enzyme's affinity for ATP
- Carbamoyl phosphate produced here enters the urea cycle, combining with ornithine (via OTC) to form citrulline
- Deficiency causes hyperammonemia (CPS I deficiency, estimated frequency ~1:62,000)
- Reaction proceeds stepwise: bicarbonate + ATP → carbonyl phosphate → carbamate → carbamoyl phosphate
CPS II — Pyrimidine Synthesis
- Found in the cytosol; uses glutamine (not free ammonia) as the nitrogen donor
- Part of a trifunctional enzyme (CAD complex: CPS II + ATCase + dihydroorotase) in mammals
- Activated by PRPP (substrate availability signal) and inhibited by UTP (end-product feedback)
- Carbamoyl phosphate produced here goes on to form orotic acid → UMP → all pyrimidines
Memory Hook
CPS I = Inner mitochondria, Inorganic ammonia (NH₄⁺), activated by N-Acetylglutamate → Urea cycle
CPS II = IIt's in the Cytosol, uses Glutamine, inhibited by UTP → pyrimidines
Sources: Harper's Illustrated Biochemistry, 32nd Ed., p. 297; Basic Medical Biochemistry, 6th Ed., Table 39.1, p. 1425
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