Involvement of the lipid and protein components of (Na(+) + K(+))-adenosine triphosphatase in the inhibitory action of alcohol.
The relative involvement of the lipid and protein moieties of (Na(+) + K(+))-activated adenosine triphosphatase in the inhibitory action of alcohol on this enzyme was investigated, using an enzyme preparation derived from the cerebral cortex of mice. Two classes of lipids are envisioned to be associated with this enzyme. One is essential for the activity of the enzyme, while the other is not. Purification or treatment with the nonionic detergent Lubrol WX increased the ATPase sensitivity to ethanol, possibly as a result of the removal of hindering lipids and contaminating proteins from the enzyme. Delipidization with deoxycholate removed both the essential and bulk lipids, and drastically reduced the activity of the enzyme. This could be subsequently reactivated with phosphatidyl serine (PS). The ethanol sensitivity of the reactivated ATPase varied with the ratio of PS to protein, and is most sensitive at 12.5mumoles PS Pi/mg when it is half-reactivated. Increasing the PS concentration cannot completely reverse the inhibition of ethanol on the reactivation. These data suggest that ethanol inhibits (Na(+) + K(+))-ATPase activity by interacting with its protein moiety. Furthermore, the sensitivity of the enzyme to ethanol is probably related to its conformation, which, in turn, is affected by its essential lipid.
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Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D008055:Lipids / Q000145:classification / Q000502:physiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011092:Polyethylene Glycols / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D008055:Lipids; D000431:Ethanol; D011092:Polyethylene Glycols; C005092:lubrol; D000254:Sodium-Potassium-Exchanging ATPase