ALAD condenses 2 dALAs to form PBG

Stable Identifier
R-HSA-189439
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
Two molecules of ALA condense to form porphobilinogen (PBG)
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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
10706561 Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria

Akagi, R, Shimizu, R, Furuyama, K, Doss, MO, Sassa, S

Hepatology 2000
11032841 Mechanistic implications of mutations to the active site lysine of porphobilinogen synthase

Mitchell, LW, Volin, M, Martins, J, Jaffe, EK

J Biol Chem 2001
Participants
Input
Participant Of
Catalyst Activity
Catalyst Activity
Title
porphobilinogen synthase activity of 8x(ALAD:Zn2+) [cytosol]
Physical Entity
Activity
Orthologous Events
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Created