ETHANOL METABOLISM IN THE LIVER

Summary: Ethanol elimination by the liver, a relatively constant process, may be increased at high concentrations of ethanol, when certain substances like fructose or pyruvate are metabolized together with ethanol or after prolonged exposure for ethanol. The metabolic effects on the liver are different at high and at low concentrations of ethanol. A number of enzymes or enzyme systems, – liver alcohol dehydrogenase, catalase and mixed-function oxidase – can in vitro catalyze the oxidation of ethanol, but little is known about the actual role of each enzyme at different metabolic conditions. The existence of more than one pathway for ethanol metabolism in the liver is now becomming increasingly evident, but whether the non-ADH mediated ethanol oxidation occurs via catalase, or mixed-function oxidase system, or both, cannot at present be decided. The activity of liver alcohol dehydrogenase cannot be induced by continuous use of ethanol. The ADH-mediated ethanol oxidation may be increased when the steady state concentration of free NADH in the cytoplasm is lowered. The rate of ethanol oxidation under in vivo conditions seems not to be determined by the rate of acetaldehyde elimination, although acetaldehyde is a product of ethanol metabolism. The reoxidation of NADH may proceed by NADH-linked substrate system, by transhydrogenation to NADP⁺ or by transporting reducing equivalents into mitochondria where they are oxidized. In this review an attempt is made to examine the effects of a number of substrates or metabolic conditions which may enhance ethanol oxidation (concentration of ethanol, fructose, pyruvate, D-glyceraldehyde, oxygen, CO₂ and 2,4-dinitrophenol) and to discuss the mechanisms involved in this action. It is concluded that the effect of pyruvate and fructose (maybe also CO₂ and D-glyceraldehyde) proceeds via ADH-mediated pathway (possibly involving the so-called “malic enzyme shuttle”) whereas the acceleration in ethanol metabolism, observed in rat liver preparations when high concentrations of ethanol are metabolized, is associated with the participation of non-ADH pathway (s) in ethanol metabolism.