Inhibition of the Mitochondrial Complex I Activity by Fatty Acid Derivatives of Vanillylamide
Fatty acid derivatives of vanillylamide were found to inhibit the mitochondrial NADH oxidase activity, but almost not the succinate oxidase activity. These results suggest that the compounds are specific inhibitors of the Complex I activity. A study using purified Complex I demonstrated that the compounds inhibit NADH-coenzyme Q reductase activity of the enzyme. However, these did not inhibit rotenone-insensitive NADH-menadione reductase activity and electron transfer from NADH through iron-sulfur centers in Complex I. Kinetic analyses with double-reciprocal plots showed that these compounds were competitive inhibitors with respect to coenzyme Q1. These findings suggest that the compounds bind to the coenzyme Q binding site of Complex I. The natures of acyl groups greatly affected the inhibitory potencies of the compounds, suggesting that the acyl group of compound is important for the binding of compound to the binding site of Complex I.
KeywordsReductase Activity Difference Spectrum Cholic Acid Mitochondrial Complex Fatty Acid Derivative
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