TY - JOUR
T1 - Inhibition by nicotinic acid of hepatic steatosis and alcohol dehydrogenase in ethanol-treated rats
AU - Baker, Herman
AU - Luisada-Opper, Anita
AU - Sorrell, Michael F.
AU - Thomson, Allan D.
AU - Frank, Oscar
N1 - Funding Information:
1 Supported in part by National Institutes of Health Grant TIAM 5236 to Division of Hepatic Metabolism and Nutrition. * Research Fellow in hepatology and nutrition. Present address: Liver Study Unit, University of Nebraska College of Medicine, 42nd and Dewey Avenue, Omaha, NE 68105. Recipient: Academic Career Development Award AM70016 from National Institutes of Health.
PY - 1973/8
Y1 - 1973/8
N2 - A single intoxicating dose of ethanol (6.0 g/kg) depressed the NAD: NADH2 ratio and increased the NADPH2: NADP ratio in rat liver. Nicotinic acid (NA) treatment prevented the accumulation of nonesterified fatty acid (NEFA), total fats, and neutral fats in the liver of rats given ethanol (EtOH); it also kept blood EtOH elevated. We postulate that NA acted by blocking EtOH oxidation-a block apparently exerted by inhibition of alcohol dehydrogenase (ADH), mediator of the principal oxidative pathway of ethanol metabolism. It was inferred that NA inhibits the enzyme by binding at the adenosine diphosphate ribose site since the addition of Zn2+ in vitro failed to reverse the NA inhibition of rat liver ADH. Blockage at the aforementioned site would thus inhibit coenzyme (NAD) binding to the apoenzyme, resulting in a block in the EtOH oxidation.
AB - A single intoxicating dose of ethanol (6.0 g/kg) depressed the NAD: NADH2 ratio and increased the NADPH2: NADP ratio in rat liver. Nicotinic acid (NA) treatment prevented the accumulation of nonesterified fatty acid (NEFA), total fats, and neutral fats in the liver of rats given ethanol (EtOH); it also kept blood EtOH elevated. We postulate that NA acted by blocking EtOH oxidation-a block apparently exerted by inhibition of alcohol dehydrogenase (ADH), mediator of the principal oxidative pathway of ethanol metabolism. It was inferred that NA inhibits the enzyme by binding at the adenosine diphosphate ribose site since the addition of Zn2+ in vitro failed to reverse the NA inhibition of rat liver ADH. Blockage at the aforementioned site would thus inhibit coenzyme (NAD) binding to the apoenzyme, resulting in a block in the EtOH oxidation.
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U2 - 10.1016/0014-4800(73)90044-0
DO - 10.1016/0014-4800(73)90044-0
M3 - Article
C2 - 4146514
AN - SCOPUS:0015830528
SN - 0014-4800
VL - 19
SP - 106
EP - 112
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 1
ER -