Abstract
Most of the ethyl alcohol consumed by humans is oxidized to acetaldehyde in the liver by the cytoplasmic alcohol dehydrogenase (ADH) system. For this ADH-catalyzed oxidation of alcohol, $NAD^+$ is required as the coenzyme and $NAD^+$becomes reduced to NADH. As the $NAD^+$becomes depleted and NADH accumulates, alcohol oxidation is reduced. For continued alcohol oxidation, the accumulated NADH must be quickly reoxidized to $NAD^+$, and it is this reoxidation of NADH to $NAD^+$that is known to be the rate-limiting step in the overall oxidation rate of alcohol The reoxidation of NADH to $NAD^+$is catalyzed by lactate dehydrogenase in the cytoplasm of hepatocytes, with pyruvate being utilized as the substrate. The pyruvate may be supplied from alanine as a result of amino acid metabolism via the urea cycle. Also, glutamine is thought to help with the supply of pyruvate indirectly, and to activate the urea cycle by producing $NH_3$. Thus, in the present study, we have examined the effects of alanine and glutamine on the alcohol oxidation rate. We utilized isolated perfused liver tissue in a system where media containing alanine and glutamine was circulated. Our results showed that when alanine (5.0mM) was added to the glucose-free infusion media, the alcohol oxidation rate was increased by 130%. Furthermore, when both glutamine and alanine were added together to the infusion media, the alcohol oxidation rate increased by as much as 190%, and the rate of urea nitrogen production increased by up to 200%. The addition of glutamine (5.0mM) alone to the infusion media did not accelerate the alcohol oxidation rate. The increases in the rates of alcohol oxidation and urea nitrogen production through the addition of alanine and glutamine indicate that these amino acids have contributed to the enhanced supply of pyruvate through the urea cycle. Based on these results, it is concluded that the dietary supplementation of alanine and glutamine could contribute to increased alcohol detoxification through the urea cycle, by enhancing the supply of pyruvate and $NAD^+$to ensure accelerated rates of alcohol oxidation.