Inhibition and regulation of rat liver L-threonine dehydrogenase by different fatty acids and their derivatives.
Rat liver L-threonine dehydrogenase is a mitochondrial enzyme which transforms L-threonine either into aminoacetone or into acetyl-CoA. We show that it is inhibited by several fatty acids and their derivatives: short chain fatty acids, L-2-hydroxybutyrate and D-3-hydroxybutyrate, long chain fatty acids, such as lauric acid, myristic acid, palmitic and stearic acids, bicarboxylic acids such as malonic acid and its derivatives methyl- and hydroxymalonic acids. The inhibition occurs at low and physiological concentrations of such compounds, which are normally present and metabolized in mitochondria. It presumably plays a role in the physiology of acetyl-CoA-dependent formation of fatty acids and ketobodies, in L-threonine-dependent gluconeogenesis, and in the regulation of L-threonine metabolism by L-threonine dehydrogenase and L-threonine deaminase.
Guerranti
R
R
Institute of Biochemistry and Enzymology, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Pagani
R
R
Neri
S
S
Errico
S V
SV
Leoncini
R
R
Marinello
E
E
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D006885:Hydroxybutyrates / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008956:Models, Chemical; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D003998:Dicarboxylic Acids; D005227:Fatty Acids; D006885:Hydroxybutyrates; D000429:Alcohol Oxidoreductases; C023159:L-threonine 3-dehydrogenase; C031570:2-hydroxybutyric acid; D020155:3-Hydroxybutyric Acid