Reaction: 4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
For diagram click here.
Other name(s): HMB-synthase; porphobilinogen deaminase; pre-uroporphyrinogen synthase; uroporphyrinogen I synthase; uroporphyrinogen I synthetase; uroporphyrinogen synthase; uroporphyrinogen synthetase; porphobilinogen ammonia-lyase (polymerizing); (4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)
Systematic name: porphobilinogen:(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)
Comments: The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 18.104.22.168 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 22.214.171.124 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9074-91-3
1. Battersby, A.R., Fookes, C.J.R., Matcham, G.W.J. and McDonald, E. Biosynthesis of the pigments of life: formation of the macrocycle. Nature 285 (1980) 17-21. [PMID: 6769048]
2. Frydman, R.B. and Feinstein, G. Studies on porphobilinogen deaminase and uroporphyrinogen 3 cosynthase from human erythrocytes. Biochim. Biophys. Acta 350 (1974) 358-373. [PMID: 4847568]
3. Levin, E.Y. and Coleman, D.L. The enzymatic conversion of porphobilinogen to uroporphyrinogen catalyzed by extracts of hematopoietic mouse spleen. J. Biol. Chem. 242 (1967) 4247-4253. [PMID: 6061709]
4. Warren, M.J. and Jordan P.M. Investigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase. Biochemistry 27 (1988) 9020-9030. [PMID: 3069132]
5. Miller, A.D., Hart, G.J., Packman, L.C. and Battersby, A.R. Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound to the protein through the sulphur atom of cysteine-242. Biochem. J. 254 (1988) 915-918. [PMID: 3196304]
6. Battersby, A.R. Tetrapyrroles: the pigments of life. Nat. Prod. Rep. 17 (2000) 507-526. [PMID: 11152419]