Learn / Metabolism
Metabolic pathways
Every FMK pathway as a clickable map. Pick one pathway to hammer it — next step, enzyme, regulator, cofactor, and the facts that get tested (NADPH and who needs it, rate-limiting steps, deficiencies) — or set it to all pathways for a mixed drill. Every answer says which enzyme and which pathway.
Urea cycle (+ the CPS-II collision)
Carbamoyl phosphate (mitochondrial)
Made from N-acetylglutamate (NAG) by NAG — obligate allosteric activator of CPS-I
NAG — obligate allosteric activator of CPS-I — Urea cycle (+ the CPS-II collision)
Without NAG, CPS-I is essentially inactive (s12). This is why the cell bothers with an obligate cofactor at all: it creates one dedicated lever that turns urea synthesis on and off with protein intake, without having to change enzyme levels.
Made from NH₄⁺ (free ammonia) + HCO₃⁻ by Carbamoyl phosphate synthetase I (CPS-I) ★
Carbamoyl phosphate synthetase I (CPS-I) ★ rate-limiting · irreversible — Urea cycle (+ the CPS-II collision)
Cofactors: 2 ATP → 2 ADP, HCO₃⁻
Activated by: N-acetylglutamate (obligate)
Deficiency: CPS-I deficiency (AR) — neonatal hyperammonemia with LOW citrulline and LOW/NORMAL orotic acid. The absent orotic acid is what separates it from OTC deficiency: the carbamoyl phosphate is never made in the first place
THE rate-limiting, committed step of the urea cycle. Mitochondrial matrix; nitrogen source is FREE ammonia. Costs 2 ATP and consumes bicarbonate — which is why urea synthesis is suppressed in acidosis in favour of glutamine (s17).
Condition cards:Carbamoyl phosphate synthetase I (CPS-I) deficiency →
Becomes Citrulline (matrix) via Ornithine transcarbamylase (OTC)
Ornithine transcarbamylase (OTC) · irreversible — Urea cycle (+ the CPS-II collision)
Deficiency: OTC deficiency — the MOST COMMON urea cycle disorder and the ONLY X-LINKED one (every other is autosomal recessive). Hyperammonemia + LOW citrulline + HIGH orotic acid. Classically a full-term male newborn, well at birth (the mother's liver cleared his nitrogen in utero), lethargic and TACHYPNEIC by 24–48 h once he metabolises his own protein, then seizing
Carbamoyl phosphate + ornithine → citrulline. This is the gate that fails in the commonest urea cycle disorder.
Condition cards:Ornithine transcarbamylase (OTC) deficiency →
Becomes Carbamoyl phosphate LEAKS into the cytosol via Spillover when OTC is blocked — carbamoyl phosphate leaks to the cytosol
Spillover when OTC is blocked — carbamoyl phosphate leaks to the cytosol — Urea cycle (+ the CPS-II collision)
CPS-I is not broken in OTC deficiency; it keeps making carbamoyl phosphate normally. With OTC unable to consume it, carbamoyl phosphate accumulates and is small enough to leak out of the mitochondrion (s15).