Reduced Triphosphopyridine Nucleotide Oxidase-catalyzed Alterations of Membrane Phospholipids

Abstract

Abstract Transient formation of phospholipid peroxides was observed during the TPNH-dependent cleavage of phospholipid-bound polyunsaturated fatty acids in liver microsomes. The peroxide functions are associated with the β position polyunsaturated fatty acids and appear to be intermediates in the chain cleavage process. The data support the conclusion that microsomes contain an enzyme system which promotes multiple peroxidative cleavage of endogenous membrane-bound polyunsaturated fatty acids, producing a variety of carbonyl-containing residues. Concomitant with the alteration of the membrane-bound phospholipids, there is evidence for major structural changes in the membrane itself. The reaction may represent an explicit metabolic function for unsaturated phospholipids during electron transport in the endoplasmic reticulum, as well as a possible alternative pathway for polyunsaturated fatty acid oxidation. On the other hand, the changes observed may be the result of chemical damage to the microsomal membrane as a consequence of TPNH-linked electron transport.