Porphobilinogen synthetase

Elder GH, Urquhart AJ (1984) Human uroporphyrinogen decarboxylase. Do tissue-specific isoenzymes exist Biochem Soc Trans 12 663-664 Elder GH, Tovey JA, Sheppard DM (1983) Purification of uroporphyrinogen decarboxylase from human erythrocytes. Biochem J 215 45-55 Farant JP, Wigfield DC (1987) Interaction of divalent metal ions with normal and lead-inhibited human erythrocytic porphobilinogen synthetase in vitro. Toxicol Appl Pharmacol 89 9-18... 

The enzyme porphobilinogen synthetase is widespread in animal and plant tissues [73, 74] and is activated by sulphydryl compounds. It condenses two molecules of ALA to form the monopyrrole porphobilinogen (PBG) [75]. 

Beside the use of a single enzyme, a cocktail of different biocatalysts can also be used in performing a domino process, provided that the enzymes do not interfere one with another. This approach was used by Scott and coworkers in the synthesis of precorrin-5 (8-61) (Scheme 8.16) [24]. Starting from 6-amino levulinic acid (ALA) 8-60, a mixture of eight different enzymes including the ALA-dehydratase to form porphobilinogen (PBG), as well as PBG deaminase and co-synthetase to furnish the tetracyclic uroporphyrinogen III (8-62) as intermediates, was employed to provide precorrin-5 (8-61) in 30% yield. 

Excessive production of liver 5-amino levulinate synthetase causes two forms of congenital porphyria. These diseases are characterized by overproduction of porphyrins and excretion of large amonnts of 5-amino levulinate and porphobilinogen. Some populations, such as Turks, are susceptible to this disease, and in these people acute attacks are brought on by barbiturates and other compounds which induce synthesis of the enzyme. 

Figure 5.5. Proposed biosynthetic sequence of ALA synthesis from glutamate to the condensation of two ALA molecules, forming porphobilinogen. The enzymes catalyzing the steps in the pathway are (1) glutamyl-tRNA synthetase, (2) glutamyl-tRNA dehydrogenase, (3) ALA synthase (GSA aminotransferase), and (4) ALA dehydratase.

Strand, L. J., Felsher, B. F., Redeker, A. G., and Marver, H. S., 1970, Heme biosynthesis in intermittent acute porphyria Decreased hepatic conversion of porphobilinogen to porphyrins and increased delta-amino-levulinic acid synthetase activity, Proc. Natl. Acad. Sci. USA 67 1315. 

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