Mechanism of Methionine Biosynthesis in Rat Liver

Abstract

Synthesis of methionine in rat liver by the B,,-independent N5-methyltetrahydropterolyltriglutamate : homocysteine methyltransfcrase reported by Wang, Hoch and Stokstad has been investigated. I n agreement with their results it was found that methionine was formed by crude rat liver supernatant fraction and dialyzed mitochondrial extract on aerobic incubation with N5-methyltetrahydr~pteroyltriglutamate, homocysteine and magnesium chloride. However, the folate derivative could not have been involved in this process since N5-[14C]methyl-tetrahydropteroyltriglutamate did not incorporate I4C into the methionkie. I n the supernatant fraction, methionine was formed by the transmethylation of endogenous betaine with added homocysteine. Rat liver supernatant fraction was found to contain 250 nmoles/ml betaine. In the mitochondrial extract, methionine formation occurred by proteolysis. It is concluded that a B,,-independent N5-rnethyltetrahydropteroyltriglntamate homocysteine methyltransferase does not occur in rat liver.It has been generally considered that methionine is formed in mammalian liver by a vitamin B,2-dependent N6-methyltetrahydrofolate-homocysteine methyltransferase [I -61. Recently, however Wang et al. [7] reported that they had observed the formation of methionine on incubation of methyltetrahydropteroyltriglutamate, homocysteine and magnesium chloride with rat liver supernatant fraction or mitochondrial extract. They interpreted these observations as indication that rat liver also possesses the alternate mechanism of methionine synthesis, catalyzed by the €%,,-independent N5-methyltetrahydropteroyltriglutamate : homocysteine methyltransferase. The validity of the conclusion of Wang et al. [7] has been examined in the study reported in the present communication. ,MATERIALS AND METHODS N6-[14C]Methyl-H,PteGlu3