Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption by normal subjects.

Aims: 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 pres...

Descripción completa

Detalles Bibliográficos
Publicado en:Alcohol & Alcoholism Vol. 44; no. 3; pp. 267 - 272
Autores principales: Badawy AA, Doughrty DM, Marsh-Richard DM, Steptoe A
Formato: Journal Article
Publicado: Oxford University Press / USA May/Jun2009
Acceso en línea:Ver este registro en EBSCOhost
Descripción
Sumario:Aims: 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 Blood samples were withdrawn 2 h later and plasma was analysed for concentrations Trp, competing amino acids (CAA) and kynurenine metabolites.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 Tip 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 Tip pyrrolase activity, was also increased by all doses of ethanol. Conclusions: We conclude that activation of liver Tip pyrrolase mediates the depletion of plasma Tip and the decrease in its availability to the brain induced by acute ethanol consumption.