Identification of the gene encoding hydroxyacid-oxoacid transhydrogenase, an enzyme that metabolizes 4-hydroxybutyrate

Tamas Kardon, Gaëtane Noël, Didier Vertommen, Emile Van Schaftingen

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

To identify the sequence of hydroxyacid-oxoacid transhydrogenase (HOT), responsible for the oxidation of 4-hydroxybutyrate in mammalian tissues, we have purified this enzyme from rat liver and obtained partial sequences of proteins coeluting with the enzymatic activity in the last purification step. One of the identified proteins was 'iron-dependent alcohol dehydrogenase', an enzyme encoded by a gene present on human chromosome 8q 13.1 and distantly related to bacterial 4-hydroxybutyrate dehydrogenases. The identification of this protein as HOT was confirmed by showing that overexpression of the mouse homologue in HEK cells resulted in the appearance of an enzyme catalyzing the α-ketoglutarate-dependent oxidation of 4-hydroxybutyrate to succinate semialdehyde.

Original languageEnglish
Pages (from-to)2347-2350
Number of pages4
JournalFEBS letters
Volume580
Issue number9
DOIs
Publication statusPublished - Apr 17 2006

Keywords

  • Organic acidurias
  • Transhydrogenase
  • d-2-Hydroxyglutarate
  • α-Ketoglutarate
  • γ-Hydroxybutyrate

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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