Metabolism of alcohol (ethanol) in man.

It is well recognized that the primary alcohol, ethanol, can be absorbed unchanged along the whole length of the digestive tract, that absorption takes place rapidly from the stomach (about zo%), and most rapidly from the small gut (about 80%). T h e rate of absorption after drinking is affected by several factors, for example the volume, concentration (10-2074 solutions are most rapidly absorbed) and nature of the alcoholic drink, the presence or absence of food in the stomach, rate of gastric emptying, pylorospasm, permeability of the gastric and intestinal tissues, individual variations. After absorption into the blood-stream, alcohol is distributed quickly throughout the total body water (Berggren & Goldberg, 1940; Harger & Hulpieu, I 956; Pappenheimer & Heisey, 1963) and is subsequently metabolized at a steady rate. A method which makes use of this property of ethanol has been successfully employed for measuring the total body water volume in human subjects (Pawan & Hoult, 1963 ; Pawan, 1965). After equilibration, normally 1-1.5 h after drinking, the alcohol concentration in any body fluid depends on the water content of that fluid (Pawan, 1967, 1970; Pawan & Grice, 1968). Over 90% of the absorbed alcohol is metabolized in the body, yielding some 7 kcal/g on complete oxidation to carbon dioxide and water, with a concomitant fall in the respiratory quotient; the remainder is excreted unchanged in the urine, expired air and sweat. The main site of metabolism of ethanol is the liver, although some other tissues, for example kidney, muscle, lung, intestine and possibly even the brain, may metabolize smaller quantities. Fig. I shows the main pathways of ethanol metabolism. It is generally believed that the rate-limiting step in the metabolism of alcohol is its conversion to acetaldehyde, a reaction catalysed by the zinc-containing enzyme, alcohol dehydrogenase (ADH). This process occurs chiefly in the soluble cytoplasm of liver cells, with nicotinamide adenine dinucleotide (NAD) acting as the hydrogen acceptor. However, particularly in alcoholics, some ethanol may be oxidized by the peroxidase-xanthine oxidase-catalase system, and possibly other oxidases both in liver and plasma (TrCmolikres & CarrC, 1960, 1961). Small amounts of alcohol may also be converted to ethyl glucuronide (Kamil, Smith & Williams, 1952), ethyl sulphate and other esters, and excreted in the urine. Orme-Johnson & Ziegler (1965) have described a ‘mixed-function enzyme’, and Lieber and his colleagues (Lieber & DeCarli, 1968a,b, 1969; Rubin, Hutterer & Lieber, 1968; Baraona & Lieber, 1970; Rubin, Bacchin, Gang & Lieber, 1970) have found liver microsomes, which comprise the smooth endoplasmic reticulum (SER), capable of oxidizing