Further studies on the formation of cardiolipin and phosphatidylglycerol in rat liver mitochondria. Effect of divalent cations and the fatty acid composition of CDP-diglyceride

Abstract

The divalent cation requirement for mitochondrial cardiolipin biosynthesis has been further investigated. The relative order of divalent cation activity was Co2+ > Mn2+ > Mg2+.

Cardiolipin was not formed in the incubations with Zn2+, Fe2+, Cu2+, Hg2+, and Ca2+. Cardiolipin synthesis in the presence of optimal concentration of Co2+ was inhibited by Ca2+.

A series of CDP-diglycerides was synthesized having differences in fatty acid chain length and degree of unsaturation. These compounds were tested in mitochondrial cardiolipin and phosphatidylglycerol synthesis. Although there were some minor differences between phosphatidylglycerol and cardiolipin synthesis, in general, saturated shorter chain CDP-diglycerides (dilauroyl and dimyristoyl) were better substrates than the longer chain dipalmitoyl and distearoyl homologues. Introduction of double bonds into distearoyl CDP-diglyceride resulted in more rapid rates of synthesis (e.g. dioleoyl and dilinoleoyl CDP-diglyceride). Significance of the results is discussed with regard to possible mechanisms of linoleic acid incorporation into rat liver cardiolipin.