Disposition of Endogenous S-Adenosylhomocysteine and Homocysteine Following Exposure to Nucleoside Analogues and Methotrexate
S-Adenosylhomocysteine (AdoHcy) is a product from and an inhibitor of S-adenosylmethionine-dependent transmethylation reactions. This compound is degraded to adenosine and L-homocysteine (Hcy) in the cell through the action of the enzyme AdoHcy hydrolase (EC 22.214.171.124.) (de la Haba & Cantoni, 1959). The view is held that the AdoHcy hydrolase reaction is the only source of Hcy in vertebrates (Cantoni & Chiang, 1980). Hcy is converted to cystathionine or is salvaged to methionine. In all tissues, except liver and kidney, the latter pathway is catalyzed by a single enzyme, which requires 5-methyl -tetrahydrofolate as methyl donor (Mudd & Levy, 1983). These metabolic relations are depicted in figure 1.
KeywordsNucleoside Analogue Extracellular Medium Cl16 Cell Adenosine Analogue Transmethylation Reaction
- Cantoni, G.L. and Chiang, P.K. (1980) in Natural Sulfur Compounds: Novel Biochemical and Structural Aspects (Cavallini. D., Gaull, G.E., and Zappia, V., Eds.) pp. 67–80, Plenum Press, New York and London.Google Scholar
- Chiang, P.K., Richard, H.H. and Cantoni, G.L. (1977) Mo1. Pharmacol. 13,939–947.Google Scholar
- de la Haba, G. and Cantoni, G.L. (1959) J. Biol. Chem. 234,. 603–608.Google Scholar
- Mudd, S.H. and Levy, H.L. (1983) in Metabolic Basis of Inherited Diseases (Standbury, J.B., Ed.) pp. 522–559, McGraw-Hill, New York.Google Scholar
- Ueland,. P.M., Refsum, H., Male, R. and Lillehaug, J.R. (1985) Cancer Res., submitted.Google Scholar