4-Hydroxynonenal inhibits Na+-K+-ATPase

Werner G. Siems, Sharon J. Hapner, Frederik J.G.M. Van Kuijk

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Hydroxynonenal binds rapidly to Na+-K+-ATPase, and this was accompanied by a decrease in measurable sulfhydryl groups and a loss of enzyme activity. The I50 value for Na+-K+-ATPase inhibition by 4-hydroxynonenal was found to be 120 μM. Although the sulfhydryl groups could be completely restored with β-mercaptoethanol during the reaction of the Na+K+-ATPase-HNE- adduct, the Na+-K+-ATPase activity was only partially restored by this reducing agent. A combination of hydroxylamine and β-mercaptoethanol yielded the greatest recovery of enzyme activity, 85% of original. Thus, 4- hydroxynonenal binding to Na+-K+-ATPase led to an irreversible decrease of enzyme activity under the conditions employed. It is hypothesized that 4- hydroxynonenal reacts with sulfhydryls at sites on the enzyme that are inaccessible by β-mercaptoethanol. Furthermore, evidence was obtained that 4-hydroxynonenal reacts with other amino acids such as lysine to form adducts that also interfere with protein function.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalFree Radical Biology and Medicine
Issue number2
StatePublished - Jan 1 1996


  • 4-Hydroxynonenal
  • Aldehydes
  • Free radicals
  • Lipid peroxidation
  • Na-K-ATPase
  • Sulfhydryl groups
  • β-Mercaptoethanol

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