Rg. Matthews et al., METHYLENETETRAHYDROFOLATE REDUCTASE AND METHIONINE SYNTHASE - BIOCHEMISTRY AND MOLECULAR-BIOLOGY, European journal of pediatrics, 157, 1998, pp. 54-59
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.