Figure 1.

Enzymatic conversion of uroporphyrinogen III to coproporphyrinogen III. At physiological substrate concentrations, the four acetate groups of uroporphyrinogen are decarboxylated in a clockwise fashion, starting with the acetate group on the asymmetric D ring (37). The enzyme will use any of the uroporphyrinogen isomers as substrates, but only the III isomer is used for heme production. Under conditions of substrate excess, decarboxylations occur in a random fashion (38). URO-D, a cytosolic 80-kDa homodimer, functions without the need for a cofactor (17, 18).