Reactome | ALAD condenses 2 dALAs to form PBG

ALAD condenses 2 dALAs to form PBG

Stable Identifier

R-HSA-189439

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

2 5-aminolevulinate => H(+) + 2 H2O + porphobilinogen, Two molecules of ALA condense to form porphobilinogen (PBG)

ReviewStatus

5/5

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5-Aminolevulinic acid dehydratase (ALAD aka porphobilinogen synthase, PBGS), catalyzes the asymmetric condensation of two molecules of ALA to form porphobilinogen (PBG). The substrate that becomes the acetyl side chain-containing half of PBG is called A-side ALA; the half that becomes the propionyl side chains and the pyrrole nitrogen is called P-ALA (Jaffe 2004). PBG is the first pyrrole formed, the precursor to all tetrapyrrole pigments such as heme and chlorophyll. There are at least eight bonds that are made or broken during this reaction. The active form of the ALAD enzyme is an octamer complexed with eight Zn2+ ions, four that are strongly bound and four that are weakly bound. The four weakly bound ones are dispensible for enzyme activity in vitro (Bevan et al. 1980; Mitchell et al. 2001).
Deficiencies of ALAD enzyme in vivo are associated with 5-aminolevulinate dehydratase-deficient porphyria (e.g., Akagi et al. 2000).

Literature References

PubMed ID	Title	Journal	Year
11032841	Mechanistic implications of mutations to the active site lysine of porphobilinogen synthase Martins, J, Mitchell, LW, Volin, M, Jaffe, EK	J Biol Chem	2001
10706561	Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria Akagi, R, Sassa, S, Doss, MO, Furuyama, K, Shimizu, R	Hepatology	2000