Long-term alcohol intake enhances ADP-ribosylation of the multifunctional enzyme, phosphoglucomutase, in rat liver.
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.
Department of Clinical Pathology, Institute of Clinical Medicine, Tsukuba University, Ibaraki, Japan.
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Nomura
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Noda
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Miyake
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Nakai
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010733:Phosphoglucomutase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000246:Adenosine Diphosphate Ribose; D000431:Ethanol; D010733:Phosphoglucomutase