Tryptophan and 5-hydroxytryptamine metabolism in alcoholism

Alcohol (ethanol) exerts a variety of effects on tryptophan (Trp) and 5-hydroxytryptamine (5-HT, serotonin) metabolism in man and experimental animals. In human healthy volunteers, acute ethanol consumption lowers circulating Trp availability to the brain, almost certainly leading to inhibition of cerebral 5-HT synthesis, possibly by enhancing liver Trp pyrrolase activity. In non-abstinent chronic alcoholics, however, Trp pyrrolase activity may be inhibited; here acute ethanol intake fails to lower circulating Trp concentration. Hepatic Trp degradation seems to be greater during abstinence, and chronic alcoholics then exhibit a decrease in Trp availability to the brain. It is, however, not clear whether this decrease and the likely associated higher liver Trp pyrrolase activity in abstinence are due to previous long-term alcohol consumption, or are inherent biological determinants of the low brain 5-HT in alcoholism. The latter possibility is supported by the recent implication of the Trp pyrrolase gene in alcoholism. In alcohol-preferring C57BL mice, the low brain [5-HT] is due to a higher liver Trp pyrrolase activity associated with a higher circulating [corticosterone]. Activity or expression of liver Trp pyrrolase and/or their induction by glucocorticoids may be important biological determinants of predisposition to alcohol consumption, and further work in this area may therefore be fruitful.