Leucine and Ethanol Oxidation

Abstract

Ethanol is metabolized to acetaldehyde by catalase in the peroxisome, by the microsomal ethanol oxidation system (MEOS) containing cytochrome P-450, which is located in the endoplasmic reticulum, and by the alcohol dehydrogenase (ADH) pathway of cytosol or the soluble fraction of the cell [1, 2]. Among these metabolic processes, ADH is a key enzyme for metabolizing ethanol, and the role of non-ADH enzymes in systemic alcohol metabolism is unclear [3]. Ethanol absorption is primarily controlled by gastric emptying because the primary region of ethanol absorption is the small intestine, and ethanol is absorbed via simple diffusion [4]; for example, slow gastric emptying leads to increases in the first-pass metabolism of ingested ethanol. Ingested ethanol is primarily metabolized in the stomach and liver. In the stomach, ADH, including the isoenzymes ADH I, III, and IV, oxidizes the ingested ethanol, but most of the ethanol (approximately 90 %) is absorbed in the small intestine. Absorptive ethanol is metabolized by ADH, including the isoenzymes ADH I, II, and III, and primarily oxidizes in the liver. In comparison, the MEOS shares many properties with other microsomal drug-metabolizing enzymes, such as P-450; therefore, MEOS pathway activity increases under high ethanol concentrations and/or after chronic ethanol consumption. Ethanol and acetaldehyde are toxic and damage cells. Catalase can oxidize ethanol in vitro with H2O2, but it may not be a major system for ethanol oxidation [2]. ADH and/or catalase, MEOS enzyme pathways metabolize ethanol to produce acetaldehyde. Acetaldehyde is a harmful compound that causes hangovers and flush. It is detoxified by aldehyde dehydrogenase (ALDH), which is primarily composed of mitochondrial low Km ALDH, including the isoenzymes ALDH I, II, III, and IV, in the liver. The acetaldehyde metabolized by ALDH is converted to acetic acid and water, resulting in detoxification. The enzymatic activities of both of ADH and ALDH are regulated by the availability of the coenzyme nicotinamide adenine dinucleotide (NAD). NAD is reduced to NADH when ethanol and acetaldehyde are oxidized by ADH and ALDH, and NADH oxidation is the limiting factor of ethanol metabolism [2]. In addition to metabolizing ethanol, NAD and NADH regulate several metabolisms as coenzymes. However, ethanol metabolism is preferable to other metabolic pathways in terms of the resulting toxicity of ethanol and its metabolite, acetaldehyde; therefore, ethanol and acetaldehyde intake affect some metabolic pathways, such as lipid, hormone, protein, and amino acid metabolism, and induce disorders such as liver failure and muscle wasting.