Unusual Kinetic Isotope Effects of Deuterium Reinforced Polyunsaturated Fatty Acids in Tocopherol-Mediated Free Radical Chain Oxidations

Lamberson, Connor R.; Xu, Libin; Muchalski, Hubert; Montenegro-Burke, J. Rafael; Shmanai, Vadim V.; Bekish, Andrei V.; McLean, John A.; Clarke, Catherine F.; Shchepinov, Mikhail S.; Porter, Ned A.

doi:10.1021/ja410569g

Cited by 42 publications

(30 citation statements)

References 36 publications

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“…[188] Furthermore,high experimental KIEs denote that the tocopherol-mediated peroxidation of fatty acids and 7-dehydrocholesterol might be promoted/supported by the tunneling of hydrogen atoms. [189,190] Tu nneling in different hydrogen-bond networks has been investigated. One of the most interesting findings is the simultaneous tunneling of protons in solid p-tert-butylcalix- [4]arene at low temperatures.…”

Section: Organic Chemistrymentioning

confidence: 99%

Atom Tunneling in Chemistry

2016

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Quantum mechanical tunneling of atoms is increasingly found to play an important role in many chemical transformations. Experimentally, atom tunneling can be indirectly detected by temperature-independent rate constants at low temperature or by enhanced kinetic isotope effects. In contrast, the influence of tunneling on the reaction rates can be monitored directly through computational investigations. The tunnel effect, for example, changes reaction paths and branching ratios, enables chemical reactions in an astrochemical environment that would be impossible by thermal transition, and influences biochemical processes.

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Section: Organic Chemistrymentioning

confidence: 99%

Atom Tunneling in Chemistry

2016

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“…Since oxidative stress is considered an important factor in the development of AD, and since D-PUFAs have been shown to reduce LPO products in other models [14][15][16][17]19,20,32,33], we investigated whether D-PUFA treatment also reduces LPO in the Aldh2 À/À mouse model of sporadic AD. D-PUFA treatment markedly decreased esterified F 2 -IsoPs by approximately 55% in both cortex and hippocampus, and prostaglandin F 2a (PGF 2a) levels by 20-25% ( Fig.…”

Section: D-pufas Reduce Lipid Peroxidation Productsmentioning

confidence: 99%

Deuterium‐reinforced polyunsaturated fatty acids improve cognition in a mouse model of sporadic Alzheimer's disease

et al. 2017

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Oxidative damage resulting from increased lipid peroxidation (LPO) is considered an important factor in the development of late onset/age-related Alzheimer’s disease (AD). Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to the reactive oxygen species-initiated chain reaction of LPO than regular hydrogenated (H-) PUFAs. We investigated the effect of D-PUFA treatment on LPO and cognitive performance in aldehyde dehydrogenase 2 (Aldh2) null mice, an established model of oxidative stress-related cognitive impairment that exhibits AD-like pathologies. Mice were fed a Western-type diet containing either D- or H-PUFAs for 18 weeks. D-PUFA treatment markedly decreased cortex and hippocampus F2-isoprostanes by approximately 55% and prostaglandin F2α by 20–25% as compared to H-PUFA treatment. D-PUFAs consistently improved performance in cognitive/memory tests, essentially resetting performance of the D-PUFA-fed Aldh2−/− mice to that of wildtype mice fed a typical laboratory diet. D-PUFAs therefore represent a promising new strategy to broadly reduce rates of LPO, and combat cognitive decline in AD.

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“…One agent, RT001, is currently in Phase I/II study as a potential treatment in FRDA (www.clinicaltrials.gov/ct2/show/NCT02445794). RT001 is deuterated linoleic acid that is chemically altered to enable its entry into the cell where it has the potential to reduce oxidative stress in the mitochondria and increase ATP production [31,32]. …”

Section: Treatment Of Frda: Medicationsmentioning

confidence: 99%

Emerging Therapies in Friedreich’s Ataxia

Aranca

Jones

Shaw

et al. 2016

Neurodegener. Dis. Manag.

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Friedreich’s ataxia (FRDA) is an inherited, progressive neurodegenerative disease that typically affects teenagers and young adults. Therapeutic strategies and disease insight have expanded rapidly over recent years, leading to hope for the FRDA population. There is currently no US FDA-approved treatment for FRDA, but advances in research of its pathogenesis have led to clinical trials of potential treatments. This article reviews emerging therapies and discusses future perspectives, including the need for more precise measures for detecting changes in neurologic symptoms as well as a disease-modifying agent.

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Unusual Kinetic Isotope Effects of Deuterium Reinforced Polyunsaturated Fatty Acids in Tocopherol-Mediated Free Radical Chain Oxidations

Cited by 42 publications

References 36 publications

Atom Tunneling in Chemistry

Atom Tunneling in Chemistry

Deuterium‐reinforced polyunsaturated fatty acids improve cognition in a mouse model of sporadic Alzheimer's disease

Emerging Therapies in Friedreich’s Ataxia

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