Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption by normal subjects.
OBJECTIVE
We have previously suggested that acute ethanol consumption by normal subjects decreases the availability of circulating tryptophan (Trp) to the brain by activating liver Trp pyrrolase, the first and rate-limiting enzyme of the (major) kynurenine pathway of Trp degradation. The aim of the present study was to examine this hypothesis further by measuring plasma levels of kynurenine metabolites following alcohol consumption.


METHODS
After an overnight fast and a light breakfast, each of 10 healthy subjects received one of five drinks (placebo and doses of ethanol of 0.2, 0.4, 0.6 and 0.8 g/kg body weight in tonic water) on five different occasions. Blood samples were withdrawn 2 h later and plasma was analysed for concentrations Trp, competing amino acids (CAA) and kynurenine metabolites.


RESULTS
Along with the depletion of plasma Trp and the decrease in its availability to the brain, as expressed by the ratio of [Trp]/[CAA], plasma kynurenine was elevated by doses of ethanol of 0.2-0.8 g/kg body weight. The ratio% of [kynurenine]/[Trp], an index of the expression of Trp pyrrolase activity, was also increased by all doses of ethanol.


CONCLUSIONS
We conclude that activation of liver Trp pyrrolase mediates the depletion of plasma Trp and the decrease in its availability to the brain induced by acute ethanol consumption.
Badawy
Abdulla A-B
AA
Cardiff School of Health Sciences, University of Wales Institute Cardiff (UWIC), Wales, UK. ABadawy@uwic.ac.uk
Doughrty
Donald M
DM
Marsh-Richard
Dawn M
DM
Steptoe
Alex
A
D000328:Adult; D000428:Alcohol Drinking / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D013997:Time Factors; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers; D000431:Ethanol; D014364:Tryptophan; D014366:Tryptophan Oxygenase