title: Stimulation in vitro of vitamin B12-dependent methionine synthase by polyamines.
abstract: Vitamin B12-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 and lipids. Consequently, studies aiming at exploring the control and regulation of methionine synthase are of particular interest. Here we report the modulation of enzyme activity in vitro by polyamines. Although putrescine, cadaverine, spermine and spermidine all stimulated enzyme activity, the last two were the most potent, causing increases in enzyme activity up to 400%. The EC50 for spermine was determined as 8 microM and for spermidine 40 microM. The physiological concentration for spermine has been reported to be 15-19 microM. Spermine was found to increase both the Km and the V(max) with respect to methyltetrahydrofolate for the enzyme. These data support the hypothesis that spermine and spermidine are feedback regulators of methionine synthase both in vivo and in vitro and are consistent with the polyamines' regulating cell signalling pathways.
authors.affiliation: University-Industry Centre for Pharmaceutical Research, School of Pharmacy, University of London, U.K.
authors.forename: S H
authors.initials: SH
authors.lastname: Kenyon
authors.forename: A
authors.initials: A
authors.lastname: Nicolaou
authors.forename: T
authors.initials: T
authors.lastname: Ast
authors.forename: W A
authors.initials: WA
authors.lastname: Gibbons
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002103:Cadaverine / Q000494:pharmacology; D004789:Enzyme Activation; D005246:Feedback; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008956:Models, Chemical; D011073:Polyamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology; D014805:Vitamin B 12 / Q000494:pharmacology*
chemical_list: D011073:Polyamines; D013096:Spermine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D002103:Cadaverine; D014805:Vitamin B 12; D011700:Putrescine