Uroporphyrinogen synthase

Figure 32-6. Conversion of porphobilinogen to uroporphyrinogens. Uroporphyrinogen synthase I is also called porphobilinogen (PBG) deaminase or hydroxy-methylbilane (HMB) synthase.

Subsequent reactions occur in the cytoplasm and they are irreversible. Two molecules of 8-aminolevulinate are condensed by the enzyme porphobilinogen synthase to form the trisubstituted pyrrole porphobilinogen. Two enzymes, uroporphyrinogen synthase and uroporphyrinogen cosynthase, condense four molecules of porphobilinogen to the porphyrin uroporphyrinogen III. 

ALA-dehydratase, urosynthase (syn. PBG-deaminase, hydroxymethylbilane synthase or pre-uroporphyrinogen synthase), uro-cosynthase or uro-decarboxylase. 

Figure 32-8. Steps in the biosynthesis of the porphyrin derivatives from porphobiiinogen. Uroporphyrinogen i synthase is aiso caiied porphobiiinogen deaminase or hydroxymethyibiiane synthase.

Acute Intermittent Porphyria Uroporphyrinogen-I Synthase Deficiency... 

The tetrapyrrole structure characteristic of the porphyrins is produced in the next steps of the synthetic pathway. Hydroxyme-thylbilane synthase catalyzes the linkage of four porphobilinogen molecules and cleavage of an NH2 group to yield uroporphyrinogen III. 

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

Porphobilinogen synthase Urocanate hydratase 3-Hydroxypalmitoyl-[ACP] dehydratase Uroporphyrinogen 111 synthase... 

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. 

The pyrrole monomer porphobilinogen arises from the condensation of two molecules of S-aminolevulinate with the ions of two water molecules. This reaction is catalyzed by S-aminolevulinate dehydrase. Condensation of four porphobilinogen molecules yields the branchpoint compound in tetrapyrrole synthesis, uroporphyrinogen III. This is a complex reaction requiring two enzymes Uroporphyrinogen I synthase, which catalyzes a head-to-tail condensation... 

Mechanism of polymerization in a linear tetrapyrrole. Four molecules of porphobilinogen undergo a head-to-tail condensation catalyzed by uroporphyrinogen 1 synthase to yield a tetrapyrrole. Asterisks indicate nitrogen and carbon atoms derived from glycine the others are derived from succinyl-CoA. 

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. 

D-12) Uroporphyrinogen I synthase deficiency (acute intermittent porphyria). 

Congenital erythropoietic porphyria CEP Uroporphyrinogen tit synthase autosomal recessive... 

Acute intermittent porphyria AtP Uroporphyrinogen I synthase autosomal dominant... 

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