Methionine adenosyltransferase in man: evidence for multiple forms.

Optimum conditions are presented for the assay of methionine adenosyltransferase (ATP:l-methionine S-adenosyltransferase, EC 2.5.1.6) in human erythrocytes and in human cultured fibroblasts and long-term lymphoid cell lines. The enzymes are similar in having an acidic pH optimum (5.2–5.7) and in being inhibited by more than 10 mm Mg²⁺ in excess of ATP. In contrast, the transferase of human liver, studied previously, is most active at pH 6.8 and requires 100 mm excess Mg²⁺ for greatest activity.Chromatography on DEAE-cellulose has been utilized to demonstrate that the transferases of liver, erythrocytes, cultured fibroblasts, and cultured lymphoid cell lines are different molecular forms. The liver enzyme, which chromatographs mainly as a single sharp peak, is less tightly bound to DEAE-cellulose than are the transferases of the three types of cells. Each type of cell contains a characteristic mixture of active forms of methionine adenosyltransferase; there are two major forms, present in different relative proportions.It is proposed that the liver enzyme is under separate genetic control from the transferases of erythrocytes and cultured cells. This would explain the presence, in two children with persistent hypermethioninemia and demonstrated deficiency of hepatic methionine adenosyltransferase, of normal amounts of transferase activity in erythrocytes, cultured fibroblasts, and cultured lymphoid cell lines.