Porphobilinogen synthase

porphobilinogen synthase
Identifiers
EC number 4.2.1.24
CAS number 9036-37-7
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Delta-aminolevulinic acid dehydratase
Identifiers
Symbol ALAD
Entrez 210
HUGO 395
OMIM 125270
RefSeq NM_001003945
UniProt P13716
Other data
EC number 4.2.1.24
Locus Chr. 9 q32
ALAD
high resolution crystal structure of a mg2-dependent 5-aminolevulinic acid dehydratase
Identifiers
Symbol ALAD
Pfam PF00490
Pfam clan CL0036
InterPro IPR001731
PROSITE PDOC00153
SCOP 1aw5

Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate dehydratase) synthesizes porphobilinogen through the asymmetric condensation of two molecules of aminolevulinic acid. All natural tetrapyrroles, including hemes, chlorophylls and vitamin B12, share porphobilinogen as a common precursor.

It is involved in the second step of the metabolism of porphyrin.

Deficiency

A deficiency of porphobilinogen synthase is usually acquired (rather than hereditary) and and can be caused by heavy metal poisoning, especially lead poisoning, as the enzyme is very susceptible to inhibition by heavy metals.[1]

Hereditary insufficiency of porphobilinogen synthase is called porphobilinogen synthase (or ALA dehydratase) deficiency poprhyria. It is an extremely rare cause of porphyria,[2] with less than 10 cases ever reported.[3]

Lead poisoning works on the cellular level by binding to this enzyme, rendering it useless.

References

  1. ^ ALA dehydratase reaction, from NetBiochem at the University of Utah. Last modified 1/5/95
  2. ^ Jaffe EK, Stith L (February 2007). "ALAD porphyria is a conformational disease". Am. J. Hum. Genet. 80 (2): 329–37. doi:10.1086/511444. PMC 1785348. PMID 17236137. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1785348. Retrieved 2008-12-10. 
  3. ^ Overview of the Porphyrias at The Porphyrias Consortium (a part of NIH Rare Diseases Clinical Research Network (RDCRN)) Retrieved June 2011

External links

Porphyrin biosynthesis
Heme degradation
to bile

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

M: MYL

cell/phys (coag, heme, immu, gran), csfs

rbmg/mogr/tumr/hist, sysi/epon, btst

drug (B1/2/3+5+6), btst, trns
Carbon-oxygen lyases (EC 4.2) (primarily dehydratases)
4.2.1: Hydro-Lyases
4.2.2: Acting on polysaccharides
4.2.3: Acting on phosphates
4.2.99: Other
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6