Identification of the gene encoding hydroxyacid-oxoacid transhydrogenase, an enzyme that metabolizes 4-hydroxybutyrate.
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.
Kardon
Tamas
T
Université catholique de Louvain and ICP, UCL 7539, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Noël
Gaëtane
G
Vertommen
Didier
D
Schaftingen
Emile Van
EV
D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D002460:Cell Line; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D051381:Rats; D017386:Sequence Homology, Amino Acid
D006885:Hydroxybutyrates; D024101:Mitochondrial Proteins; D000429:Alcohol Oxidoreductases; C072878:hydroxyacid-oxoacid transhydrogenase