LIGATION, INHIBITION, AND ACTIVATION OF CYTOCHROME-C-OXIDASE BY FATTY-ACIDS

Free fatty acids bind to beef heart cytochrome c oxidase and induce sp ectral shifts similar to those obtained with high spin ligands. Oleic (18:1(n-9)) and linoleic (18:2(n-6)) acids induce substantial blue shi fts of the Soret peak of oxidized enzyme. Small saturated fatty acids (<15 carbon atoms) shift the Soret peak to the red, and longer chain a cids induce smaller blue shifts. Formate-induced spectral shifts are m odified by short chain fatty acids but are unaffected by longer chain fatty acids for which effects are additive with those of formate. Inhi bition by formate is partially relieved by all fatty acids tested. Pal mitic and linoleic acids increase turnover at low cytochrome c levels and decrease the K-m for cytochrome c at high cytochrome c levels. Ole ic acid protects the enzyme against acid denaturation during turnover. Bovine serum albumin produces a red shift in the oxidase Soret peak a nd inhibits turnover of the isolated enzyme. Oleic acid and serum albu min modify the electron paramagnetic resonance spectrum of oxidized ox idase, oleic acid shifting the g = 3 (cytochrome a) peak towards low f ield and albumin towards higher field strengths. The oxidase may posse ss at least two fatty acid binding sites at one of which cytochrome c binding is modulated and at another spectral changes may be induced. O ne site is close enough to the binuclear centre to interact allosteric ally with ligand binding at that centre.