Nicotinamide N-methyltransferase (NNMT) is an enzyme which transfers a methyl group from S-adenosyl-l-methionine to nicotinamide, thereby producing S-adenosylhomocysteine and 1-methylnicotinamide (pictured). Although NNMT is highly expressed in different types of tumors, its metabolic functions in cancer remain unknown.
Olesya Ulanovskaya and colleagues, The Scripps Research Institute, La Jolla, California, USA, clarified this issue. The researchers demonstrated that, in contrast to adenosyl-l-methionine, 1-methylnicotinamide does not operate as a methyl unit donor, but rather as a stable storage of methyl groups. As a consequence, by generating 1-methylnicotinamide, NNMT consumes methyl groups and, thus, reduces the ability of tumor cells to methylate target proteins such as histones. Since histones methylation crucially regulates gene expression, NNMT ultimately causes an over-expression of genes which promote tumorigenesis. NNMT is, therefore, an attractive therapeutic target to control methylation in cancer cells.
- NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink,
O. A. Ulanovskaya, A. M. Zuhl, B. F Cravatt,
Nat. Chem. Biol. 2013.