Synthesis of Cardiolipin Derivatives with Protection of the Free Hydroxyl: Its Application to the Study of Cardiolipin Stimulation of Cytochrome c Oxidase

Marsha P. Dale, Neal C. Robinson

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Abstract

Cardiolipin derivatives retaining the free hydroxyl on the polar head group were synthesized. With the use of a tetrahydropyranyl ether to protect this hydroxyl, fatty acyl substitutions were made at both of the 2-positions of cardiolipin (CL). The disubstituted derivatives were obtained in high yields. The stimulation of delipidated cytochrome c oxidase activity shows a hyperbolic dependence on the concentration of these CL derivatives. Both activation parameters, the apparent dissociation constant (&Kd,app) and the maximum change in molecular activity (ΔActmax), depend on the chain length of the tails, with less dependence on the degree of saturation. Natural CL (92% C18;2, 8% C18:1) and CL disubstituted with oleic acid (47% C18:2, 52% C18;1) were equally effective at stimulating cytochrome c oxidase activity, with an apparent dissociation constant of approximately 1 μM when incubated in 0.3% Triton X-100 and assayed in lauryl maltoside. CL disubstituted with hexanoic acid, however, is a poorer activator, with an apparent dissociation constant of 6.8 μM and a ΔActmaxthat is 50% of that achieved with natural CL. Dilysocardiolipin, with complete removal of two of the fatty acid tails, shows negligible stimulation of cytochrome c oxidase activity.

Original languageEnglish (US)
Pages (from-to)8270-8275
Number of pages6
JournalBiochemistry
Volume27
Issue number21
DOIs
StatePublished - Oct 1 1988

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ASJC Scopus subject areas

  • Biochemistry

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