Porphobilinogen deaminase is a cytoplasmic enzyme that exerts its action in the heme biosynthesis pathway. It's function is to assemble a linear tetrapyrrole, called preuroporphyrinogen, from four molecules of porphobilinogen. Preuroporphyrinogen then undergoes a series of reactions where it is circularized, selectively decarboxylated and oxidized to protoporphyrin IX, the direct precursor to heme.

Porphobilinogen deaminase was first described by Bogorad in 1958 and has since been isolated from a variety of sources including human, rat, mouse and pea among others. However, most of the structural information about this enzyme has come from recombinant strains of E. coli(2,8).

A high amount of sequence homology between species(45%) suggests that the enzymes all have similar tertiary structures and mechanisms of action. They have similar properties with optimal pH's of 8.0-8.5, turnover numbers of about .5 mol/sec*mol and Mr's of 34,000-44,000. As expected, most of the invariant residues are located in or around the active site(these are discussed in detail in the Active Site section). Other conserved residues away from the active site are important for structural stability. Leucine and alanine residues form the hydrophobic core of the enzyme, while invariant glycines reduce steric hindrance and allow for more compact folding. In addition, the enzyme contains a dipyrromethane cofactor, made from two molecules of porphobilinogen, which is a component of the active site and is essential for it's activity(2,5,8).

Porphobilinogen deaminase has also been pinpointed as the cause of the inheritable disease Acute Intermittant Porphyria. Insufficient amounts of functional porphobilinogen deaminase lead to abnormally high amounts of porphobilinogen and 5-aminolevulinic acid, which affects brain and nervous tissue(5,8). It has been shown that most mutations in the human porphobilinogen deaminase gene are single base substitutions in exons 10 and 12 resulting in amino acid substitutions in the enzyme. Any alterations in the active site, especially arginine residues, affect cofactor assembly and substrate binding making the enzyme nonfunctional. Other substitutions impair the stuctural stability of the enzyme by disrupting salt bridges or domain to domain hydrophobic interactions(1,5,6,8).