Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme (EC 4.2.1.24) that in humans is encoded by the ALAD gene. 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. Porphobilinogen synthase is the prototype morpheein. Function
It catalyzes the following reaction, the second step of the biosynthesis of porphyrin:

2 5-Aminolevulinic acid 
  
    
      
        ⇌
      
    
    {\displaystyle \rightleftharpoons }
   porphobilinogen + 2 H2OIt therefore catalyzes the condensation of 2 molecules of 5-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). This reaction is the first common step in the biosynthesis of all biological tetrapyrroles. Zinc is essential for enzymatic activity. Structure
The structural basis for allosteric regulation of Porphobilinogen synthase (PBGS) is modulation of a quaternary structure equilibrium between octamer and hexamer (via dimers), which is represented schematically as 6mer* ↔ 2mer* ↔ 2mer ↔ 8mer. The * represents a reorientation between two domains of each subunit that occurs in the dissociated state because it is sterically forbidden in the larger multimers. PBGS is encoded by a single gene and each PBGS multimer is composed of multiple copies of the same protein.
Deficiency
A deficiency of porphobilinogen synthase is usually acquired (rather than hereditary) and can be caused by heavy metal poisoning, especially lead poisoning, as the enzyme is very susceptible to inhibition by heavy metals.Hereditary insufficiency of porphobilinogen synthase is called porphobilinogen synthase (or ALA dehydratase) deficiency poprhyria. It is an extremely rare cause of porphyria, with less than 10 cases ever reported. All disease associated protein variants favor hexamer formation relative to the wild type human enzyme. PBGS as the prototype morpheein
The morpheein model of allostery exemplified by PBGS adds an additional layer of understanding to potential mechanisms for regulation of protein function and complements the increased focus that the protein science community is placing on protein structure dynamics.This model illustrates how the dynamics of phenomena such as alternate protein conformations, alternate oligomeric states, and transient protein-protein interactions can be harnessed for allosteric regulation of catalytic activity. References
External links
Human ALAD genome location and ALAD gene details page  in the UCSC Genome Browser. delta-Aminolevulinic+Acid+Dehydratase at the US National Library of Medicine Medical Subject Headings (MeSH)
http://www.omim.org/entry/125270?search=pbgs&highlight=pbgs


== Further reading ==