Tryptophan metabolism in alcoholism.
Studies of tryptophan (Trp) metabolism in relation to the serotonin status in alcoholism are of 2 types: (1) those related to the pharmacological effects of ethanol; (2) those concerning the serotonin status in the absence of alcohol intake. In experimental animals, acute and chronic ethanol administration and subsequent withdrawal exert a variety of effects on brain serotonin synthesis and turnover mediated by corresponding changes in Trp availability to the brain secondarily mainly to modulation of liver Trp pyrrolase (TP) activity. Alcohol-preferring mice and rats exhibit a central serotonin deficiency caused by, or in some cases associated with, a higher TP activity. Liver TP also appears to be a target of ethanol in man and evidence has recently emerged that alcoholics with positive family history are serotonin-deficient because of a lower availability of circulating Trp to the brain. Acutely, ethanol depletes brain serotonin in normal subjects, which may explain alcohol-induced aggression in susceptible individuals and also the incidence of depression in alcoholism. Trp availability to the brain is increased before the appearance of the alcohol-withdrawal syndrome in man, raising the possibility that the associated behavioural disturbances may involve the excitotoxic Trp metabolite quinolinate. Further studies of the Trp and serotonin status in relation to these important clinical features of alcohol dependence and alcoholism may therefore yield fruitful results.
Badawy
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Cardiff Community Healthcare NHS Trust, Biomedical Research Laboratory, Whitchurch Hospital, Wales, United Kingdom.
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D051381:Rats; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D012701:Serotonin; D014364:Tryptophan; D014366:Tryptophan Oxygenase