title: Tryptophan metabolism in alcoholism.
abstract: Acute and chronic alcohol (ethanol) intake and subsequent withdrawal exert major effects on tryptophan (Trp) metabolism and disposition in human subjects and experimental animals. In rats, activity of the rate-limiting enzyme of Trp degradation, liver Trp pyrrolase (TP), is enhanced by acute, but inhibited after chronic, ethanol administration, then enhanced during withdrawal. These changes lead to alterations in brain serotonin synthesis and turnover mediated by corresponding changes in circulating Trp availability to the brain. A low brain-serotonin concentration characterizes the alcohol-preferring C57BL/6J mouse strain and many alcohol-preferring rat lines. In this mouse strain, liver TP enhancement causes the serotonin decrease. In man, acute ethanol intake inhibits brain serotonin synthesis by activating liver TP. This may explain alcohol-induced depression, aggression and loss of control in susceptible individuals. Chronic alcohol intake in dependent subjects may be associated with liver TP inhibition and a consequent enhancement of brain serotonin synthesis, whereas subsequent withdrawal may induce the opposite effects. The excitotoxic Trp metabolite quinolinate may play a role in the behavioural disturbances of the alcohol-withdrawal syndrome. Some abstinent alcoholics may have a central serotonin deficiency, which they correct by liver TP inhibition through drinking. Further studies of the Trp and serotonin metabolic status in long-term abstinence in general and in relation to personality characteristics, alcoholism typology and genetic factors in particular may yield important information which should facilitate the development of more effective screening, and preventative and therapeutic strategies in this area of mental health.
authors.affiliation: Cardiff and Vale NHS Trust, Biomedical Research Laboratory, Whitchurch Hospital, Cardiff CF14 7XB, UK. abdulla.badawy@cdffcom-tr.wales.nhs.uk
authors.forename: Abdulla A-B
authors.initials: AA
authors.lastname: Badawy