Kinetic studies of the regulation of mitochondrial malate dehydrogenase by citrate.
Mitochondrial malate dehydrogenase shows a complex regulation pattern in the presence of citrate. Previously published results indicate that this enzyme is activated by citrate in the NAD(+)----NADH direction and inhibited in the opposite direction. Moreover, high concentrations of L-malate or oxaloacetate produce deviations from the Michaelis-Menten behaviour. Results reported in this paper clearly show that citrate both activates and inhibits mitochondrial malate dehydrogenase in the same direction (NAD(+)----NADH), and in the same reaction medium, depending on substrate concentration. This surprising effect has made it necessary to propose a new kinetic mechanism that extends those previously suggested and allows us to explain both the citrate effect (activating or inhibitory) and the effect of high concentrations of L-malate and oxaloacetate.
Gelpí
J L
JL
Department de Bioquímica i Fisiologia, Facultat de Química, Universitat de Barcelona, Spain.
Dordal
A
A
Montserrat
J
J
Mazo
A
A
Cortés
A
A
D000818:Animals; D001667:Binding, Competitive; D002645:Chickens; D002951:Citrates / Q000378:metabolism* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D008432:Mathematical Computing; D008930:Mitochondria, Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010071:Oxaloacetates / Q000378:metabolism
D002951:Citrates; D008293:Malates; D010071:Oxaloacetates; D009243:NAD; C030298:malic acid; D008291:Malate Dehydrogenase