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 synthesis (porphyrias)
δ-Aminolevulinic acid (ALA)
Made from Glycine + succinyl-CoA by ALA synthase (ALAS1 liver / ALAS2 erythroid) ★
ALA synthase (ALAS1 liver / ALAS2 erythroid) ★ rate-limiting · irreversible — Heme synthesis (porphyrias)
Cofactors: Pyridoxal phosphate (B₆)
Activated by: Drugs & hormones that induce P450 (barbiturates, anticonvulsants, rifampin, alcohol, OCPs/progesterone); Fasting / low carbohydrate
Inhibited by: Heme (represses ALAS1 transcription and blocks its mitochondrial import); Glucose (the 'glucose effect')
Deficiency: ALAS2 (erythroid isoform) — X-linked sideroblastic anemia: microcytic anemia with ring sideroblasts and iron-loaded mitochondria; responds to pyridoxine
Mitochondrial matrix; ties heme to the TCA cycle via succinyl-CoA. ALAS2 (X-linked, erythroid) is iron-regulated — its mutations cause X-linked sideroblastic anemia, not a porphyria. Isoniazid antagonises B₆ and can impair the step.
Condition cards:X-linked sideroblastic anemia →Isoniazid-induced vitamin B6 (pyridoxine) deficiency →IV hemin (hematin) for acute porphyria →Givosiran →
Becomes Porphobilinogen (PBG) via ALA dehydratase (porphobilinogen synthase)
ALA dehydratase (porphobilinogen synthase) — Heme synthesis (porphyrias)
Cofactors: Zn²⁺
Inhibited by: LEAD (displaces zinc) — lead-sensitive step #1
Deficiency: ALA dehydratase-deficiency porphyria (rare, AR) — neurovisceral only; ALA ↑ with normal PBG, like lead poisoning
2 ALA → PBG. Cytosol.
Condition cards:Lead poisoning →ALA dehydratase deficiency porphyria →