Long–Term Alcohol Intake Enhances Adp–Ribosylation of the Multifunctional Enzyme, Phosphoglucomutase, in Rat Liver

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Adenosine diphosphate (ADP)–ribosylation is a posttranslational protein modification that, in turn, alters several regulatory proteins in mammalian cells. We demonstrated that long–term alcohol intake enhanced the ADP–ribosylation of a 58–kd protein in rat liver plasma membranes. To assess the biological significance of this phenomenon, we partially purified the 58–kd acceptor protein from solubilized rat liver homogenates by two sequential preparative high–pressure liquid chromatographies. Microsequencing revealed that it was phosphoglucomutase (PGM) (EC 5,4,2,2). This enzyme underwent negligible auto ADP–ribosylation, but the ADP–ribosylation was remarkably increased by adding rat liver plasma membranes. The extent of the increase was greater in alcohol–fed rats than in pair–fed controls, suggesting enhanced enzyme activities toward ADP–ribosylation of PGM after chronic alcohol consumption. Several important enzymes are ADP–ribosylated, after which their activities are modified. The results of this study showed that PGM is a novel substrate for ADP–ribosylation in the liver and that the ADP–ribosylation is increased after chronic alcohol consumption. In view of the variety of roles of PGM in the liver (carbohydrate metabolism and Ca2+ homeostasis), specific roles of this modification in terms of the effects of alcohol on hepatocytes may deserve further investigation.