Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 50, Issue 1, Pages 130-138Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2010.10.690
Keywords
Isotope effect; Lipid autoxidation; Oxidative stress; Coenzyme Q; Ubiquinone; Free radicals
Funding
- National Institutes of Health, General Medical Sciences [GM45952]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM045952] Funding Source: NIH RePORTER
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The facile abstraction of bis-allylic hydrogens from polyunsaturated fatty acids (PUFAs) is the hallmark chemistry responsible for initiation and propagation of autoxidation reactions. The products of these autoxidation reactions can form cross-links to other membrane components and damage proteins and nucleic acids. We report that PUFAs deuterated at bis-allylic sites are much more resistant to autoxidation reactions, because of the isotope effect. This is shown using coenzyme Q-deficient Saccharomyces cerevisiae coq mutants with defects in the biosynthesis of coenzyme Q (Q). Q functions in respiratory energy metabolism and also functions as a lipid-soluble antioxidant. Yeast coq mutants incubated in the presence of the PUFA alpha-linolenic or linoleic acid exhibit 99% loss of colony formation after 4 h, demonstrating a profound loss of viability. In contrast, coq mutants treated with monounsaturated oleic acid or with one of the deuterated PUFAs, 11,11-D-2-linoleic or 11,11,14,14-D-4-alpha-linolenic acid, retain viability similar to wild-type yeast. Deuterated PUFAs also confer protection to wild-type yeast subjected to heat stress. These results indicate that isotope-reinforced PUFAs are stabilized compared to standard PUFAs, and they protect coq mutants and wild-type yeast cells against the toxic effects of lipid autoxidation products. These findings suggest new approaches to controlling ROS-inflicted cellular damage and oxidative stress. (C) 2010 Elsevier Inc. All rights reserved.
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