EC 2.5.1.61 - Hydroxymethylbilane synthase

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IntEnz Enzyme Nomenclature
EC 2.5.1.61

Names

Accepted name:
hydroxymethylbilane synthase
Other names:
HMB-synthase
porphobilinogen ammonia-lyase (polymerizing) [misleading]
porphobilinogen deaminase
pre-uroporphyrinogen synthase
uroporphyrinogen I synthase
uroporphyrinogen I synthetase
uroporphyrinogen synthase
uroporphyrinogen synthetase
(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)
Systematic name:
porphobilinogen:(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)

Reaction

Cofactor

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 4.2.1.75 (uroporphyrinogen-III synthase), which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00461
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004418
CAS Registry Number: 9074-91-3
UniProtKB/Swiss-Prot: (477) [show] [UniProt]

References

  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: 17-21 (1980). [PMID: 6769048]
  2. Frydman, R.B. and Feinstein, G.
    Studies on porphobilinogen deaminase and uroporphyrinogen 3 cosynthase from human erythrocytes.
    Biochim. Biophys. Acta 350: 358-373 (1974). [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: 4247-4253 (1967). [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: 9020-9030 (1988). [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: 915-918 (1988). [PMID: 3196304]
  6. Battersby, A.R.
    Tetrapyrroles: the pigments of life.
    Nat. Prod. Rep. 17: 507-526 (2000). [PMID: 11152419]

[EC 2.5.1.61 created 1972 as EC 4.3.1.8, transferred 2003 to EC 2.5.1.61]