Vitamins, Sugars and Ethanol Metabolism in Man

Abstract

IT is generally accepted that the rate-limiting step in the metabolism of alcohol (ethanol) in man is the conversion of alcohol into acetaldehyde^1–3. This reaction is believed to occur chiefly in the soluble cytoplasm of liver cells^4,5, and is catalysed by alcohol dehydrogenase (ADH)⁶, NAD acting as hydrogen acceptor^7,8. The part played by the interesting ethanol-oxidizing system recently discovered⁹ in the microsomes of liver cells may be significant, but requires further evaluation. The availability of unreduced NAD in the cell sap seems to be important^10,11, because NADH competes with NAD for binding sites on the enzyme ADH and, in sufficient concentration, may inhibit the rate of ethanol dehydrogenation¹². The NADH produced in the initial oxidative step in ethanol metabolism must therefore be continually reoxidized by various oxidation-reduction systems for the reaction to proceed¹³. In the cell sap of liver cells the reoxidation of NADH may be coupled to the reduction of pyruvate to lactate^3,8, and to the reductive synthesis¹⁴, elongation and saturation of fatty acids; but perhaps the most important route for reoxidation of the NADH involves the mitochondrial flavoprotei–cytochrome electron transfer system coupled with phosphorylating oxidation^15–17. The “carrier” of the hydrogen equivalents from NADH across the relatively impermeable mitochondrial membranes may be substances like alpha-glycero-phosphate¹⁷, beta-hydroxybutyrate^18,19, malate and glutamate²⁰, which serve to “shuttle” hydrogen from the extramitochondrial NADH, across the mitochondrial membranes, for oxidation in the intra-mitochondrial compartment.