Vitamin B-12-dependent methionine synthase is an important enzyme for
sulphur amino acid, folate polyamine metabolism, S-adenosylmethionine
metabolism and also in the methylation pathway of DNA, RNA, proteins a
nd lipids. Consequently, studies aiming at exploring the control and r
egulation of methionine synthase are of particular interest. Here we r
eport the modulation of enzyme activity in vitro by polyamines, Althou
gh putrescine, cadaverine, spermine and spermidine all stimulated enzy
me activity, the last two were the most potent, causing increases in e
nzyme activity up to 400 %. The EC(50) for spermine was determined as
8 mu M and for spermidine 40 mu M. The physiological concentration for
spermine has been reported to be 15-19 mu M. Spermine was found to in
crease both the K-m and the V-max with respect to methyltetrahydrofola
te for the enzyme. These data support the hypothesis that spermine and
spermidine are feedback regulators of methionine synthase both in viv
o and in vitro and are consistent with the polyamines' regulating cell
signalling pathways.