Competing Methyltransferase Systems

Abstract

Abstract Large differences between the transfer RNA methyl-transferase capacity of adult organs and their fetal counterparts, as well as between tumor tissues and normal tissues, have been observed. This is in part due to the presence of natural inhibitors of the tRNA methyltransferases in normal adult tissues. An inhibitory system present in the liver, kidney, and pancreas of adult rabbit and rat has been identified. The inhibitory effect of extracts of these organs on the tRNA methyltransferases is due to the presence of an enzyme which methylates glycine to yield sarcosine and S-adenosylhomocysteine (S-adenosylmethionine: glycine N-methyltransferase). The glycine methyltransferase not only competes with the tRNA methyltransferases for the methyl donor S-adenosylmethionine but its product S-adenosylhomocysteine is a potent inhibitor of the tRNA methyltransferases and a relatively weak inhibitor of the glycine methyltransferase. The glycine methyltransferase is found only in those organs where elevated levels of S-adenosylmethionine-synthesizing enzyme have been observed. It is present at either very low levels or not at all in fetal organs and several tumor tissues. It is postulated that the glycine methyltransferase serves a role in regulating the relative levels of S-adenosylmethionine and S-adenosylhomocysteine, thus exerting some control over those methyltransferases whose activity is more sensitive to the action of S-adenosylhomocysteine.