Tryptophan Metabolism and Disposition in Relation to Alcohol and Alcoholism

Abstract

Tryptophan (Trp) metabolism and disposition in relation to alcohol and alcoholism are briefly reviewed. The changes observed could generally be classified into those: (1) exerted by acute or chronic alcohol administration and/or subsequent withdrawal; (2) already present in the absence of alcohol consumption, such as in naive alcohol-preferring animals or in abstinent alcoholics. In normal rats, acute ethanol administration activates liver Trp pyrrolase and exerts a biphasic effect on brain 5-HT (5-hydroxytryptamine or serotonin) synthesis, whereas chronic ethanol administration and subsequent withdrawal exert opposite effects on 5-HT synthesis mediated by corresponding changes in liver Trp pyrrolase activity. A cerebral 5-HT deficiency has been demonstrated in the alcohol-preferring C57BL mouse strain and in a number of alcohol-preferring rat lines, the mechanism of which is understood only in two models; the C57BL mouse strain has a higher liver Trp pyrrolase activity and the P rat line from Indiana has a lower density of serotonergic fibres in cerebral cortex. In man, acute ethanol intake lowers circulating [Trp] and its availability to the brain, almost certainly by activating liver Trp pyrrolase. Some evidence exists for possible inhibition of pyrrolase activity in non-abstinent chronic alcoholics. Evidence in recently abstinent alcoholics suggests that Trp availability to the brain may be impaired and that this may be particularly so in patients with positive family history. Exploration of this latter possibility may be important in understanding the biological basis of predisposition to alcoholism.