Hydroxymethylbilane synthase (HMBS)

Hydroxymethylbilane synthase (HMBS) is a monomeric enzyme (EC 2.5.1.61), also known as porphobilinogen deaminase, responsible for the third step in heme biosynthesis. It catalyzes the stepwise condensation of four porphobilinogen molecules into hydroxymethylbilane, releasing ammonia in the process[1][3][4][5][7][9]. HMBS is essential for heme synthesis; mutations cause the metabolic disorder acute intermittent porphyria (AIP) by leading to the accumulation of toxic precursor molecules and can also lead to a distinctive, well-differentiated subtype of hepatocellular carcinoma when biallelic inactivation occurs[6][8]. HMBS structure consists of three distinct domains, coordinated by a covalently attached dipyrromethane cofactor, with several key residues regulating the catalytic process and product release[1][5][7][9]. Disease management includes avoiding precipitating drugs and the use of intravenous hematin, while diagnosis typically relies on clinical symptoms, accumulation of heme precursors, and genetic analysis[8][9].

Other names

Porphobilinogen deaminasePBGDPBG-DHMBSPre-uroporphyrinogen synthaseuroporphyrinogen I synthaseHEM3ENCEPLENCEPPORCUPS

Hematin: Downregulates hepatic heme biosynthesis, reducing accumulation of porphyrin precursors in cases of HMBS deficiency