Small amounts of isotope-reinforced polyunsaturated fatty acids suppress lipid autoxidation
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- 作者：Shauna Hill ; Connor R. Lamberson ; Libin Xu ; R ; y To ; Hui S. Tsui ; Vadim V. Shmanai ; Andrei V. Bekish ; Agape M. Awad ; Beth N. Marbois ; Charles R. Cantor ; Ned A. Porter ; Catherine F. Clarke ; Mikhail S. Shchepinov
- 关键词：¦ÁLnn ; ¦Á-linolenic acid (C18 ; 3 ; n&ndash ; 3) ; ARA ; arachidonic acid (C20 ; 4 ; n&ndash ; 6) ; BHT ; butylated hydroxytoluene ; D ; deuterium ; D2-Lin ; 11 ; 11-D2-linoleic acid or ethyl ester ; D4-¦ÁLnn ; 11 ; 11 ; 14 ; 14-D4-¦Á-linolenic acid ; EPA ; eicosapentaenoic acid (C22
- 刊名：Free Radical Biology and Medicine
- 出版年：2012
- 出版时间：15 August, 2012
- 年：2012
- 卷：53
- 期：4
- 页码：893-906
- 全文大小：1781 K
文摘
Polyunsaturated fatty acids (PUFAs) undergo autoxidation and generate reactive carbonyl compounds that are toxic to cells and associated with apoptotic cell death, age-related neurodegenerative diseases, and atherosclerosis. PUFA autoxidation is initiated by the abstraction of bis-allylic hydrogen atoms. Replacement of the bis-allylic hydrogen atoms with deuterium atoms (termed site-specific isotope-reinforcement) arrests PUFA autoxidation due to the isotope effect. Kinetic competition experiments show that the kinetic isotope effect for the propagation rate constant of Lin autoxidation compared to that of 11,11-D2-Lin is 12.8¡À0.6. We investigate the effects of different isotope-reinforced PUFAs and natural PUFAs on the viability of coenzyme Q-deficient Saccharomyces cerevisiae coq mutants and wild-type yeast subjected to copper stress. Cells treated with a C11-BODIPY fluorescent probe to monitor lipid oxidation products show that lipid peroxidation precedes the loss of viability due to H-PUFA toxicity. We show that replacement of just one bis-allylic hydrogen atom with deuterium is sufficient to arrest lipid autoxidation. In contrast, PUFAs reinforced with two deuterium atoms at mono-allylic sites remain susceptible to autoxidation. Surprisingly, yeast treated with a mixture of approximately 20 % :80 % isotope-reinforced D-PUFA:natural H-PUFA are protected from lipid autoxidation-mediated cell killing. The findings reported here show that inclusion of only a small fraction of PUFAs deuterated at the bis-allylic sites is sufficient to profoundly inhibit the chain reaction of nondeuterated PUFAs in yeast.