PERTURBATION OF BIOCHEMICAL TRANSMETHYLATIONS BY 3-DEAZAADENOSINE INVIVO

Elevated levels of adenosylmethionine (AdoMet) and adenosylhomocysteine (AdoHcy) were observed in livers of rats injected with 3-deazaadenosine, an inhibitor of adenosylhomocysteine hydrolase. A marked appearance of 3-deazaadenosylhomocysteine was observed. The ratio of AdoMet/AdoHcy in the liver was reduced from a normal value of 4.5 to 1.6 after two injections, and to 1.3 after three injections. Perturbation of biochemical transmethylations was achieved in rats injected with 3-deazaadenosine, as evidenced by: (a) a reduction in the level of creatine in the liver; (b) a decrease in the urinary excretion of 3-methoxy-4-hydroxymandelic acid; and (c) a drastic reduction in the methylation of lipids, as measured by methyl-3H-incorporation from [methyl-3H]AdoMet. These observations support the hypothesis that the ratio AdoMet/AdoHcy may be of critical importance in the regulation of biological methylations. The enzyme, adenosylhomocysteine hydrolase, therefore, may be considered a prime biological target in terms of in vivo regulation of transmethylation reactions. © 1979.