EFFECTS OF ADENOSINE DIALDEHYDE ON S-ADENOSYLHOMOCYSTEINE HYDROLASE AND S-ADENOSYLMETHIONINE-DEPENDENT TRANSMETHYLATIONS IN MOUSE L929 CELLS
- 1 January 1984
- journal article
- research article
- Vol. 25 (3) , 418-424
Abstract
Adenosine dialdehyde (2''-O-[(R)-formyl(adenin-9-yl)methyl]-(R)-glyceraldehyde), which is formed by periodate oxidation of adenosine, was a potent inhibitor of S-adenosylhomocysteine hydrolase (AdoHcy hydrolase) in mouse [neoplastic fibroblast] L929 cells. The inhibitory effects of adenosine dialdehyde on AdoHcy hydrolase were time-dependent, having a rapid onset with complete inhibition occurring with a 15-min incubation period. When mouse L929 cells were preincubated with adenosine dialdehyde for 15 min, then transferred to fresh medium, the AdoHcy hydrolase activity returned to control values within 16 h. When cycloheximide, an inhibitor of protein synthesis, was included in the incubation medium, recovery of AdoHcy hydrolase activity was not prevented, suggesting that the recovery of enzyme activity was probably due to slow reversal of the inhibitor-enzyme complex. The inhibition of AdoHcy hydrolase by adenosine dialdehyde resulted in a time-dependent increase in endogenous AdoHcy levels. After an initial 15-min lag time, the concentration of AdoHcy continued to increase, reaching a maximum of 1200 pmol/mg of protein in 12 h. A slight increase in AdoMet levels was observed. Incubation of mouse L929 cells with adenosine dialdehyde also caused an inhibition of lipid methylation and protein carboxylmethylation which resulted from the compound''s effect on AdoHcy hydrolase and the subsequent buildup of endogenous AdoHcy levels. Under the conditions that produce inhibition of AdoHcy hydrolase and AdoMet-dependent methyltransferase, adenosine dialdehyde had no effect on RNA or DNA synthesis. Therefore, adenosine dialdehyde appears to be a useful chemical probe with which to study the physiological role of AdoMet-dependent methylations.This publication has 13 references indexed in Scilit:
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