METHYLENETETRAHYDROFOLATE REDUCTASE AND METHIONINE SYNTHASE - BIOCHEMISTRY AND MOLECULAR-BIOLOGY

Methylenetetrahydrofolate reductase and cobalamin-dependent methionine synthase catalyze the penultimate and ultimate steps in the biosynthe sis of methionine in prokaryotes, and are required for the regeneratio n of the methyl group of methionine in mammals. Defects in either of t hese enzymes can lead to hyperhomocysteinemia. The sequences of the hu man methylenetetrahydrofolate reductase and methionine synthase are no w known, and show clear homology with their bacterial analogues. Mutat ions in both enzymes that are known to occur in humans and to be assoc iated with hyperhomocysteinemia affect residues that are conserved in the bacterial enzymes. Structure/function studies on the bacterial pro teins, summarized in this review, are therefore relevant to the functi on of the human enzymes; in particular studies on the effects of bacte rial mutations analogous to those causing hyperhomocysteinemia in huma n may shed light on the defects associated with these mutations.