Uroporphyrinogen-III synthase

Formation of this intermediate step requires a second enzyme, uroporphyrinogen III synthase. If this enzyme is lacking, the wrong isomer, uroporphyrinogen I, is formed. 

This enzyme [EC 4.3.1.8], also known as hydroxymethyl-bilane synthase, catalyzes the dipyrromethane-depen-dent reaction of four porphobilinogen molecules with water to produce hydroxymethylbilane and four molecules of ammonia. In the presence of a second enzyme, uroporphyrinogen-III synthase [EC 4.2.1.75], the product is cycUzed to form uroporphyrinogen-III. 

Affected enzyme ALA-dehy- dratase Hydroxymethyl-bilane synthase Uroporphyrinogen III synthase Uroporphyrinogen decarboxylase Coproporphyrinogen oxidase Protoporphyrinogen oxidase Ferrochelatase... 

This disease is caused by a deficiency in uroporphyrinogen III synthase. 

Uroporphyrinogen III synthase 1 Uroporphyrinogen III Congenital erythropoietic porphyria (AR,10q26) J... 

Figure 3 The synthesis of heme from glycine and sucdnyl-CoA. The enzymes are ALAS, S-aminolevulinic acid (ALA) synthase ALAD, S-aminolevulinic acid dehydratase PBGD, porphobilinogen deaminase UROIIIS, uroporphyrinogen III synthase UROD, uroporphyrinogen decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase and FECH, ferrochelatase.

Mathews MA, Schubert HL, Whitby FG, Alexander KJ, 31. Schadick K, Bergonia HA, Phillips JD, Hill CP. Crystal structure of human uroporphyrinogen III synthase. EMBO J. 2001 20 5832-5839. 

The genes for all the enzymes of human heme biosynthesis have been characterized (Table 32-2), and the structures of 5-aminolevulinic acid dehydratase (ALAD), hydroxymethyl-bilane synthase (HMBS), uroporphyrinogen-III synthase (UROS), uroporphyrinogen decarboxylase (UROD), and ferrochelatase (FECH) have been determined by x-ray crys-tallography. - - ... 

Synthesis of uroporphyrinogen I and III. The latter is the biologically useful isomer, and its formation requires the action of uroporphyrinogen-III synthase. Ac, -CH2COOH P, -CH2CH2COOH. 

Figure 2-1 Schematic representation of the heme biosynthetic pathway in mammalian cells. ALAS, S-aminolevulinate synthase PBGS, porphobiUnogen synthase PBGD, porphobilinogen deaminase Uro III synthase, uroporphyrinogen III synthase Uro III decarboxylase, uroporphyrinogen III decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase FC, ferrochelatase.

Uroporphyrinogen III synthase (EC 4.2.1.75). This enzyme converts hydroxymethylbilane into uropor-... 

Warner CA, Yoo HW, Roberts AG, Desnick RJ (1992) Congenital erythropoietic porphyria identification and expression of exonic mutations in the uroporphyrinogen III synthase gene. J Clin Invest 89 693-700. 

Vannini, V, Rodriguez, A., Vera, J.L., et al. (2011) Cloning and heterologous expression of Lactobacillus reuteri uroporphyrinogen III synthase/methyltransferase gene (cobA/hemD) preUminary characterization. Biotechnol Lett... 

---