| Type: | Family | Name: | Porphobilinogen deaminase |
| Description: | Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway []. The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin [].The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase () to charge a tRNA with glutamate, glutamyl-tRNA reductase () to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase () to catalyse a transamination reaction to produce ALA.The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase, ) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase, ) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase () to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase () [].Porphobilinogen deaminase (also known as hydroxymethylbilane synthase, ) functions during the second stage of tetrapyrrole biosynthesis. This enzyme catalyses the polymerisation of four PBG molecules into the tetrapyrrole structure, preuroporphyrinogen, with the concomitant release of four molecules of ammonia. This enzyme uses a unique dipyrro-methane cofactor made from two molecules of PBG, which is covalently attached to a cysteine side chain. The tetrapyrrole product is synthesized in an ordered, sequential fashion, by initial attachment of the first pyrrole unit (ring A) to the cofactor, followed by subsequent additions of the remaining pyrrole units (rings B, C, D) to the growing pyrrole chain []. The link between the pyrrole ring and the cofactor is broken once all the pyrroles have been added. This enzyme is folded into three distinct domains that enclose a single, large active site that makes use of an aspartic acid as its one essential catalytic residue, acting as a general acid/base during catalysis [, ]. A deficiency of hydroxymethylbilane synthase is implicated in the neuropathic disease, Acute Intermittent Porphyria (AIP) []. A deficiency of hydroxymethylbilane synthase alters vegetative and reproductive development and causes lesions in Arabidopsis []. | Short Name: | HemC |
