Uroporphyrinogen

Uroporphyrinogen refers to a class of porphyrinogen intermediates in the tetrapyrrole biosynthesis pathway that leads to heme, chlorophyll, and related compounds. These molecules are colorless precursors that contain multiple carboxyl side chains and exist mainly in two stereoisomeric forms: uroporphyrinogen I and uroporphyrinogen III. The biologically productive route in most animals produces the III isomer, which is then converted downstream to heme and other essential porphyrin products.

In the heme biosynthesis pathway, porphobilinogen is linked to form hydroxymethylbilane, which is cyclized by uroporphyrinogen III synthase to yield uroporphyrinogen III. If hydroxymethylbilane cyclizes nonenzymatically, or if the synthase is defective, uroporphyrinogen I can form instead. The III isomer is the substrate for subsequent decarboxylation and oxidation steps that produce coproporphyrinogen III, protoporphyrin IX, and finally heme, whereas the I isomer is not efficiently incorporated into heme and tends to accumulate in certain porphyrias.

Clinical relevance includes disorders of porphyrin metabolism. Deficiency of uroporphyrinogen III synthase causes congenital erythropoietic porphyria, characterized by accumulation of uroporphyrinogen I and photosensitivity. Deficiencies or dysfunction in uroporphyrinogen decarboxylase can lead to porphyria cutanea tarda, featuring elevated porphyrins and light sensitivity. Outside disease, uroporphyrinogens are typically oxidized to colored porphyrins, which can be measured in diagnostic porphyrin testing.