INHIBITION OF METHIONINE ADENOSYLTRANSFERASE BY THE POLYAMINES

The effect of the polyamines, putrescine, spermine, and spermidine, on the activity of extrahepatic methionine adenosyltransferase (MAT II) was studied. The polyamines inhibited MAT II activity at concentration s equal to or greater than 5 mM. Combinations of polyamines were more effective than individual polyamines in inhibiting MAT activity; maxim um inhibition approached 80% with combinations of all three polyamines . S-Adenosylmethionine (AdoMet), P-i, and PPi, the products of the MAT reaction, are known to be synergistic inhibitors of the nonhepatic fo rm of the enzyme. Combinations of polyamines plus P-i and/or PPi induc ed an additive inhibition of the enzyme. AdoMet plus polyamines also r esulted in significant inhibition, but inhibition plateaued at about 8 0%, indicating the presence of a protective mechanism to maintain AdoM et synthesis. Extrahepatic MAT from human and rat tissues was inhibite d by the polyamines, indicating that this phenomenon is not species sp ecific. In addition, we examined the effect of polyamines on MAT activ ity in resting and activated human lymphocytes that were shown to diff er in the relative expression of MAT II subunits. Although MAT from mi togen (phytohemagglutinin, PHA)- and superantigen (Staphylococcal ente rotoxin B, SEB)-stimulated lymphocytes were similarly inhibited by 10 mM polyamines, at lower concentrations of polyamines (1-5 mM), MAT fro m SEB-stimulated cells appeared to be more susceptible to inhibition b y the polyamines. Inasmuch as SEB is a more physiological stimulator o f T cells than PHA, the data suggest a possible role of polyamines in regulating MAT activity. (C) 1997 Academic Press.