Isotope-reinforced polyunsaturated fatty acids protect yeast cells from oxidative stress.
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 α-linolenic or linoleic acid exhibit 99% loss of colony formation after 4h, 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)-α-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.
Hill
Shauna
S
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Hirano
Kathleen
K
Shmanai
Vadim V
VV
Marbois
Beth N
BN
Vidovic
Dragoslav
D
Bekish
Andrei V
AV
Kay
Bradley
B
Tse
Vincent
V
Fine
Jonathan
J
Clarke
Catherine F
CF
Shchepinov
Mikhail S
MS
D000975:Antioxidants / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects* / Q000235:genetics; D003903:Deuterium / Q000737:chemistry / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics; D007553:Isotope Labeling; D030781:Organisms, Genetically Modified; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000235:genetics; D015003:Yeasts / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D014451:Ubiquinone; D003903:Deuterium