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.
Heme degradation & bilirubin (jaundice)
Hepatocyte bilirubin (ligandin)
Made from Bilirubin–albumin (plasma) by Sinusoidal uptake (OATP) → ligandin (Y protein)
Sinusoidal uptake (OATP) → ligandin (Y protein) — Heme degradation & bilirubin (jaundice)
Deficiency: Rotor syndrome (AR) — defective hepatic storage/OATP transport: benign conjugated hyperbilirubinemia, liver NOT pigmented (vs Dubin-Johnson)
Facilitated transport across the basolateral membrane; ligandin shuttles it to the smooth ER.
Condition cards:Rotor syndrome →
Becomes Bilirubin diglucuronide (conjugated, 'direct') via Bilirubin UDP-glucuronosyltransferase (UGT1A1)
Bilirubin UDP-glucuronosyltransferase (UGT1A1) · irreversible — Heme degradation & bilirubin (jaundice)
Cofactors: 2 × UDP-glucuronic acid
Activated by: Phenobarbital (induces residual enzyme — Crigler-Najjar II)
Deficiency: Gilbert (mild promoter polymorphism, ~30% activity, 3–7% of people; unconjugated bilirubin rises with fasting/illness; benign) · Crigler-Najjar I (complete absence, AR; severe unconjugated hyperbilirubinemia, kernicterus; phototherapy/transplant) · Crigler-Najjar II (partial; responds to phenobarbital) · physiologic neonatal jaundice (immature enzyme + high RBC turnover; days 2–3, resolves ~2 weeks; jaundice in the FIRST 24 h is never physiologic)
Conjugation makes bilirubin water-soluble and non-toxic. Physiologically immature for ~2 weeks after birth.
Condition cards:Hepatic (hepatocellular) jaundice →Gilbert syndrome →Crigler-Najjar syndrome type I →Crigler-Najjar syndrome type II →Physiologic neonatal jaundice →Breast milk jaundice →Breastfeeding jaundice →