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Metabolic Fate of 1,3-Butanediol in the Rat: Conversion to ß-Hydroxybutyrate^{1 ,2}

Department of Biochemistry, University of Nebraska Medical Center and Veterans Administration Hospital, Omaha, Nebraska 68105

High speed supernatants of extracts of rat liver exhibited an NAD⁺-dependent oxidation of both 1,3-butanediol (BD) and ethanol at pH 10 similar to that shown by crystalline horse liver alcohol dehydrogenase. Inhibition of rat liver alcohol dehydrogenase in vivo by intraperitoneal injection of pyrazole or n-butyraldoxime prior to sacrifice for liver slice experiments brought about inhibition of ketone body production from BD. Ethanol and BD oxidation by rat liver extracts in vitro was also strongly inhibited by pyrazole. The ethanol and BD dehydrogenase activities of rat liver extracts were coincident as judged by cellulose polyacetate strip electrophoresis. The products of the BD oxidation catalyzed by either rat liver extracts or crystalline horse liver alcohol dehydrogenase yielded azine derivatives with N-methyl benzothiazolone hydrazone hydrochloride which were identical to the corresponding derivative of 3-hydroxybutenal (aldol). The formation of D-ß-hydroxybutyrate from BD by rat liver extracts was strongly dependent on NAD⁺ and was nearly completely inhibited by pyrazole. It is therefore concluded BD is catabolized to ß-hydroxybutyrate in the liver; liver alcohol dehydrogenase catalyzes the initial oxidative step in the cytosol, yielding aldol as an intermediate. Aldol is then further oxidized to ß-hydroxybutyrate where it enters known metabolic sequences.

KEY WORDS: • 1,3-butanediol • ß-hydroxybutyric acid • acetoacetic acid • liver • metabolism

¹ This study was supported by Public Health Service Grant AM 13782-02 from the National Institute of Arthritis and Metabolic Diseases and by a grant from the Celanese Corporation and V.A. Hospital.

² Presented in part at the 1970 Midwest Regional Meeting of the American Chemical Society, Lincoln, Nebraska, October, 1970.

Manuscript received 27 May 1971.