Isotope‐Reinforced Polyunsaturated Fatty Acids Protect Yeast Cells from Oxidative Stress

Abstract

Polyunsaturated fatty acids (PUFAs) are exquisitely sensitive to autoxidation damage. The enhanced vulnerability of PUFAs to such autoxidation stems from the labile nature of the bis‐allylic hydrogen atoms. PUFAs synthesized to contain Deuterium atoms uniquely at the bis‐allylic sites (termed isotope‐reinforced PUFAs) would be expected to be more resistant to autoxidation reactions due to the isotope effect. This hypothesis was tested by making use of yeast coq mutants with defects in biosynthesis of coenzyme Q (CoQ, or ubiquinone). CoQ plays a well‐known role in respiratory energy metabolism and also functions as a lipid soluble chain terminating antioxidant. Although yeast cannot synthesize PUFAs, they are able to incorporate exogenously supplied PUFAs. Yeast coq mutants incubated in the presence of linolenic acid (C18:3) exhibit profound loss of viability as ascertained by greater than 99% loss of colony formation at 4 hours. In contrast, the coq mutants treated with the isotope‐reinforced linolenic acid (bis‐allylic D4‐C18:3) retain 80–90% viability, a value similar to wild‐type or CoQ‐replete yeast. These results indicate that isotope reinforced PUFAs are stabilized as compared to standard PUFAs, and the coq mutant yeast cells containing the D4‐linolenic acid are protected against the toxic effects of lipid autoxidation products. This research was supported by NIH GM45952.