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Consequences of the Inhibition of Cardiolipin Metabolism in Haemophilus parainfluenzae

Biochemistry Department, University of Kentucky Medical Center, Lexington, Kentucky 40506

ABSTRACT

Examination of phospholipid metabolism in Haemophilus parainfluenzae with inhibitors of various cellular functions indicated that macromolecular synthesis and lipid metabolism can be dissociated at least for a short time. Two classes of inhibitors have relatively specific effects on cardiolipin (CL) metabolism. Pentachlorophenol and p-hydroxymercuribenzoate blocked CL synthesis but allowed CL hydrolysis to phosphatidic acid and phosphatidyl glycerol (PG); 3,3',4,5'-tetrachlorosalicylanilide (TCS) and carbonyl cyanide m-chlorophenylhydrazone (m-CCCP) blocked CL hydrolysis with the stoichiometric accumulation of CL. It appeared as if TCS and m-CCCP inhibited a vital activity coupled with the hydrolysis of CL by the highly active, CL-specific phospholipase D found in this organism. Because TCS and m-CCCP are thought to act by destroying the proton gradient thereby interrupting energy-dependent transport, it is possible that a highly active portion of the cellular CL could be coupled to some phase of this process.