Uroporphyrinogen III synthase (UROS)

Uroporphyrinogen III synthase (UROS) is a cytosolic enzyme that catalyzes the fourth step in heme biosynthesis, converting hydroxymethylbilane (a linear tetrapyrrole) into uroporphyrinogen III via cyclization and inversion of the D-ring. This reaction creates the macrocyclic precursor essential for pathways forming heme, chlorophyll, siroheme, cobalamin (vitamin B12), and other biologically crucial tetrapyrroles[5][4][1][3][2]. UROS functions as a lyase (cyclase), folding into two structural domains with the active site between them, and employs a network of hydrogen bonding interactions for substrate orientation and catalysis[3][1]. Deficiency or genetic mutation of this enzyme causes congenital erythropoietic porphyria (Gunther's disease), characterized by accumulation of toxic porphyrins, leading to photosensitivity, hemolytic anemia, and cutaneous manifestations[6][5]. No therapies currently target UROS directly, but its activity is a diagnostic biomarker for related porphyrias and gene mutations are used in patient selection and disease confirmation[6].

Other names

uroporphyrinogen-III synthaseuro’gen III synthaseU3SURO-synthaseEC 4.2.1.75

Catalysis of cyclization and isomerization (D-ring inversion) of hydroxymethylbilane to uroporphyrinogen III