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

T. 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

Fingerprint

Hydroxybutyrates
Gene encoding
Enzymes
Genes
Oxidation
Proteins
Alcohol Dehydrogenase
Human Chromosomes
Succinic Acid
Chromosomes
Liver
Purification
Rats
Iron
Tissue
hydroxyacid-oxoacid transhydrogenase

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Identification of the gene encoding hydroxyacid-oxoacid transhydrogenase, an enzyme that metabolizes 4-hydroxybutyrate. / Kardon, T.; Noël, Gaëtane; Vertommen, Didier; Van Schaftingen, Emile.

In: FEBS Letters, Vol. 580, No. 9, 17.04.2006, p. 2347-2350.

Research output: Contribution to journalArticle

Kardon, T. ; Noël, Gaëtane ; Vertommen, Didier ; Van Schaftingen, Emile. / Identification of the gene encoding hydroxyacid-oxoacid transhydrogenase, an enzyme that metabolizes 4-hydroxybutyrate. In: FEBS Letters. 2006 ; Vol. 580, No. 9. pp. 2347-2350.
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