Figure 2.

Inhibition of UROD by uroporphomethene leads to the accumulation of porphyrins and manifestations of disease in PCT. Under normal conditions, UROD converts uroporphyrinogen to coproporphyrinogen by a series of 4 sequential decarboxylations. In the presence of iron and free radicals, uroporphyrinogen is partially oxidized, leading to the formation of a uroporphomethene inhibitor of UROD. Decarboxylated uroporphyrinogen intermediates subsequently accumulate and auto-oxidize to their corresponding porphyrins, predominantly uroporphyrins. Photosensitive porphyrins accumulate in the plasma and are responsible for the cutaneous manifestations of PCT. Fe, iron; PCT, porphyria cutanea tarda; UROD, uroporphyrinogen decarboxylase; ROS, reactive oxygen species. Professional illustration by Patrick Lane, ScEYEnce Studios.