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.

Pathway

Heme degradation & bilirubin (jaundice) · Macrophages of spleen, liver (Kupffer) and marrow → plasma (albumin) → hepatocyte smooth ER → bile → colon → stool and urine. Enzymes sit beside the arrows; a ★ marks the rate-limiting step. The map scrolls inside its panel.

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Heme degradation & bilirubin (jaundice)

Bilirubin diglucuronide (conjugated, 'direct')

Made from Hepatocyte bilirubin (ligandin) by 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 →

Becomes Bile → small intestine via Canalicular excretion (MRP2, active transport) ★

Canalicular excretion (MRP2, active transport) ★ rate-limiting — Heme degradation & bilirubin (jaundice)

Deficiency: Dubin-Johnson syndrome (AR, MRP2) — benign conjugated hyperbilirubinemia with a grossly BLACK liver

Rate-limiting for hepatic bilirubin handling and the step most easily overwhelmed by obstruction — conjugated bilirubin backs up into blood and urine (dark urine, bilirubinuria).

Condition cards:Intrahepatic cholestasis →Dubin-Johnson syndrome →