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...

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Published in:Alcohol & Alcoholism Vol. 44; no. 3; pp. 267 - 272
Main Authors: Badawy AA, Doughrty DM, Marsh-Richard DM, Steptoe A
Format: Journal Article
Published: Oxford University Press / USA May/Jun2009
Online Access:View this record in EBSCOhost
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      dt: May/Jun2009
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      pub: Oxford University Press / USA
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        atl: Activation of liver tryptophan pyrrolase mediates the decrease in tryptophan availability to the brain after acute alcohol consumption by normal subjects.
      aug:
        au:
          Badawy AA
          Doughrty DM
          Marsh-Richard DM
          Steptoe A
        affil: Cardiff School of Health Sciences, University of Wales Institute Cardiff (UWIC), Wales, UK. ABadawy@uwic.ac.uk
      sug:
        subj:
          Alcohol Drinking
          Brain Metabolism
          Liver
          Tryptophan Metabolism
          Oxidoreductases Metabolism
          Adult
          Biological Markers Blood
          Brain Drug Effects
          Biochemical Phenomena Drug Effects
          Biochemical Phenomena Physiology
          Ethanol Administration and Dosage
          Female
          Liver Drug Effects
          Male
          Time Factors
          Tryptophan Blood
          Oxidoreductases Blood
          Young Adult
          Adult: 19-44 years
          Female
          Male
      ab: 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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