Figure 44-2. Heme biosynthetic pathway involving (1) ALAS, (2) ALAD,
(3) PBGD, (4) UROS, (5) UROD, (6) CPO, (7) PPO, and (8) Ferrochelatase.
HMB = hydroxymethylbilane; CM = carboxymethyl; CE = carboxyethyl; M =
methyl; V = vinyl.
steps, uroporphyrinogen decarboxylase (UROD) recognizes either isomer
URO I or III and removes specific carboxyl groups leaving coproporphyrino-
gen I or III, respectively. Coproporphyrinogen oxidase (CPO) acts exclu-
sively on the type III isomer of coproporphyrinogen; after its substrate enters
the mitochondrion CPO catalyzes the conversion of COPRO III to protopor-
phyrinogen III. This intermediate is oxidized by protoporphyrinogen oxi-
dase (PPO) to form protoporphyrin IX. In the final step of heme synthesis, the
enzyme ferrochelatase inserts a ferrous iron into water-insoluble protopor-
phyrin IX. The excess protoporphyrin IX not converted to heme is removed via
biliary excretion into the intestine.