Induction of Differentiation of 3T3-L1 Fibroblasts to Adipocytes by 3-Deazaadenosine and Insulin

Abstract

3-Deazaadenosine (dzAdo), an analog of adenosine, is a potent proximal inhibitor of S-adenosylmethionine-dependent transmethylation reactions (1–3). A variety of transmethylation reactions have been shown to be inhibited by dzAdo because of its ability to act as an alternative substrate and also as an inhibitor of S-adenosylhomocysteine hydrolase, which hydrolyzes S-adenosylhomocysteine to adenosine and L-homocysteine. A unique feature of S-adenosylhomocysteine hydrolase is that it can synthesize a novel S-nucleosidylhomocysteine analog by condensing a nucleoside with L-homocysteine because the equilibrium of the reaction favors the synthetic direction (1–5). When dzAdo is administered to cells or animals, the net result is the accumulation of S-adenosylhomocysteine and S-3-deazaadenosylhomocysteine, both of which are known potent inhibitors of transmethylation reactions (6–11).