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Identification of N-Acetyltaurine as a Novel Metabolite of Ethanol through Metabolomics-Guided Biochemical Analysis
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Identification of N-Acetyltaurine as a Novel Metabolite of Ethanol through Metabolomics-Guided Biochemical Analysis

Identification of N-Acetyltaurine as a Novel Metabolite of Ethanol through Metabolomics-Guided Biochemical Analysis
News

Identification of N-Acetyltaurine as a Novel Metabolite of Ethanol through Metabolomics-Guided Biochemical Analysis

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Abstract
Histological and biochemical examinations of ethanol-exposed mice indicated that the Cyp2e1-null mice were more resistant to ethanol-induced hepatic steatosis and transaminase activity than the wild-type mice, suggesting CYP2E1 contributes to ethanol-induced toxicity. Metabolomic analysis of urinary metabolites revealed time- and dose-dependent changes in the chemical composition of urine. Along with ethyl glucuronide (EtG), ethyl sulfate (EtS), N-acetyltaurine (NAT) was identified as a urinary metabolite that is highly responsive to ethanol exposure. Subsequent stable isotope labeling analysis using deuterated ethanol determined that NAT is a novel metabolite of ethanol. Among three possible substrates of NAT biosynthesis (taurine, acetyl-CoA and acetate), the level of taurine was significantly reduced while the levels of acetyl-CoA and acetate were dramatically increased after ethanol exposure. In vitro incubation assays suggested that acetate is the main precursor of NAT, which was further confirmed by the stable isotope labeling analysis using deuterated acetate. The incubations of tissues and cellular fractions with taurine and acetate indicated that the kidney has the highest NAT synthase activity among tested organs while the cytosol is the main site of NAT biosynthesis inside the cell. Overall, the combination of biochemical and metabolomic analysis revealed NAT is a novel metabolite of ethanol and a potential biomarker of hyperacetatemia.

The article is published online in the Journal of Biological Chemistry and is free to access.

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