5-AMINOLEVULINATE SYNTHASE: MODULATION OF THE COFACTOR CHEMISTRY BY THE PROTEIN SCAFFOLD

Ferreira G.C.

 

University of South Florida, College of Medicine, Tampa, FL, USA

 

 

5-Aminolevulinate synthase, a pyridoxal 5'-phosphate-dependent enzyme of the α-oxoamine synthase family, catalyzes the first step of the heme biosynthetic pathway in mammalian cells. This reaction entails the condensation of glycine with succinyl-coenzyme A to yield 5-aminolevulinate, carbon dioxide and CoA. In the past few years, rapid scanning-stopped-flow spectroscopy and chemical quenched-flow studies of the ALAS reaction, under single- and multi-turnover conditions, have provided important results for the interpretation of the catalytic mechanism. In particular, the role of the protein scaffold in modulating the chemical reactivity of the pyridoxal 5'-phosphate cofactor and, thus, the catalytic pathway of ALAS has been investigated in our laboratory using a combination of circular permutation, transient kinetics and global analysis of the kinetic data.