Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis

Abstract

5-Aminolaevulinate synthetase catalyses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C—C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate ( a ) undergoes decarboxylation to give the carbanion ( b ) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine. In pathway B, loss of a C2 hydrogen atom gives another type of carbanion ( c ) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C—C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine. Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.