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Identification of the gene encoding hydroxyacid‐oxoacid transhydrogenase, an enzyme that metabolizes 4‐hydroxybutyrate
Author(s) -
Kardon Tamas,
Noël Gaëtane,
Vertommen Didier,
Van Schaftingen Emile
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.02.082
Subject(s) - enzyme , biochemistry , gene , alcohol dehydrogenase , chemistry , biology , dehydrogenase , microbiology and biotechnology
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.