Mechanism of the control of (Na+ + K+)-ATPase by long-chain acyl coenzyme A.
Long-chain fatty acid esters of CoA activate (Na+ + K+)-ATPase (the sodium pump) when ATP is suboptimal. To explore the nature of the interactions of these CoA derivatives with the pump, reversible effects of palmitoyl-CoA on the purified membrane-bound kidney enzyme were studied under conditions where interference from the irreversible membrane-damaging effect of the compound was ruled out. With 50 microM ATP, while saturating palmitoyl-CoA increased (Na+ + K+)-ATPase activity, it caused partial inhibition of Na+-ATPase activity without affecting the steady-state level of the phosphoenzyme. Palmitoyl-CoA did not change the K0.5 of ATP for Na+-ATPase, but it altered the complex Na+ activation curve to suggest the antagonism of the low-affinity, but not the high-affinity, Na+ sites. At a low ATP concentration (0.5 microM), K+ inhibited Na+-ATPase as expected. In the presence of palmitoyl-CoA and 0.5 microM ATP, however, K+ became an activator, as it is at high ATP concentrations. The activating effect of palmitoyl-CoA on (Na+ + K+)-ATPase activity was reduced with increasing pH (6.5-8.5), but its inhibitory effect on Na+-ATPase was not altered in this pH range. The data show two distinct actions of palmitoyl-CoA: 1) blockade of the extracellular "allosteric" Na+ sites whose exact role in the control of the pump is yet to be determined, and 2) activation of the pump through increased rate of K+ deocclusion. Since in their latter action the fatty acid esters of CoA are far more effective than ATP at a low-affinity regulatory site, we suggest that these CoA derivatives may be the physiological ligands of this regulatory site of the pump.
Huang
W H
WH
Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Wang
Y
Y
Askari
A
A
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004285:Dogs; D004789:Enzyme Activation; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000214:Acyl Coenzyme A; D010171:Palmitoyl Coenzyme A; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium