Effect of vanadium ions on ATP citrate lyase.
We have shown previously that vanadium ions (vanadate and vanadyl) inhibit autophosphorylation of histidine but not that of serine in ATP citrate lyase (ACL). Here we report the results concerning the effect of monovanadate (+ oligomers), decavanadate as well as vanadyl on the activity of ACL of the rat liver. Susceptibility of ACL to inhibition by vanadate was rather low. Vanadate at concentration 10(-4) mol/l inhibited ACL by only 10% and at 10(-3) mol/l concentration monovanadate inhibited ACL by 37%. Decavanadate had comparable potency to inhibit ACL. So was vanadyl which produced 20%, 32% and 66% inhibition at 10(-4) mol/l, 10(-3) mol/l and 10(-2) mol/l concentrations, respectively. From the kinetic data it appears that inhibition by mono- and deca-vanadate of ACL with respect to both ATP and citrate was of competitive nature. Vanadyl inhibited ACL noncompetitively with respect to these substrates. However, all three species of vanadium ions inhibited ACL noncompetitively with respect to CoA. Endogenous (auto)phosphorylation of the ACL histidine as well as its response to vanadate depended on the presence of he substrate (citrate + CoA). The kinetic characteristics of vanadium ions action of ACL was compared with that previously demonstrated for vanadium inhibition of succinyl-CoA synthetase. Plausibility of our hypothesis that inhibition of histidyl phosphorylation at the catalytic site may be a common mechanism by which vanadium ions suppress the activity of the histidyl containing enzymes catalyzing the phosphoryl transfer is discussed.
Krivánek
J
J
Institute of Physiology, Academy of Sciences of Czech Republic, Prague.
D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D003065:Coenzyme A / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D014638:Vanadates / Q000494:pharmacology*
D002951:Citrates; D019343:Citric Acid; D014638:Vanadates; D006639:Histidine; D000244:Adenosine Diphosphate; D001275:ATP Citrate (pro-S)-Lyase; D003065:Coenzyme A