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

Kardon, Tamas;Noël, Gaëtane;Vertommen, Didier;Van Schaftingen, Emile
(2006) FEBS Letters — Vol. 580, n° 9, p. 2347-2350 (2006)

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Authors
  • Kardon, TamasUCLouvain
    Author
  • Noël, GaëtaneUCLouvain
    Author
  • Author
  • Van Schaftingen, EmileUCLouvain
    Author
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 alpha-ketoglutarate-dependent oxidation of 4-hydroxybutyrate to succinate semialdehyde.
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Citations

Kardon, T., Noël, G., Vertommen, D., & Van Schaftingen, E. (2006). Identification of the gene encoding hydroxyacid-oxoacid transhydrogenase, an enzyme that metabolizes 4-hydroxybutyrate. FEBS Letters, 580(9), 2347-2350. https://doi.org/10.1016/j.febslet.2006.02.082 (Original work published 2006)