TY - JOUR
T1 - Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle
AU - Boros, László G.
AU - D'Agostino, Dominic P.
AU - Katz, Howard E.
AU - Roth, Justine P.
AU - Meuillet, Emmanuelle J.
AU - Somlyai, Gábor
N1 - Funding Information:
The work was supported by the Hirshberg Foundation for Pancreatic Cancer Research , the UCLA Clinical & Translational Science Institute ( UL1TR000124 ) and UCLA Center for Excellence in Pancreatic Diseases – Metabolomics Core ( 1-P01 AT003960-01A1 ) to LGB. Targeted 13 C tracer drug efficacy marker data diagnostics for cancer were partially supported by the European Regional Development Fund, Central Hungary Operative Program, New Széchenyi Plan (KMOP-1.1.4-11/A-2011-01-05) to GS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
We thank Eszter Boros and Szandra Szentjóbi-Szabó for their technical help in preparing the manuscript including visual fitting of Table 1 and Fig. 1.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - The naturally occurring isotope of hydrogen (1H), deuterium (2H), could have an important biological role. Deuterium depleted water delays tumor progression in mice, dogs, cats and humans. Hydratase enzymes of the tricarboxylic acid (TCA) cycle control cell growth and deplete deuterium from redox cofactors, fatty acids and DNA, which undergo hydride ion and hydrogen atom transfer reactions. A model is proposed that emphasizes the terminal complex of mitochondrial electron transport chain reducing molecular oxygen to deuterium depleted water (DDW); this affects gluconeogenesis as well as fatty acid oxidation. In the former, the DDW is thought to diminish the deuteration of sugar-phosphates in the DNA backbone, helping to preserve stability of hydrogen bond networks, possibly protecting against aneuploidy and resisting strand breaks, occurring upon exposure to radiation and certain anticancer chemotherapeutics. DDW is proposed here to link cancer prevention and treatment using natural ketogenic diets, low deuterium drinking water, as well as DDW production as the mitochondrial downstream mechanism of targeted anti-cancer drugs such as Avastin and Glivec. The role of 2H in biology is a potential missing link to the elusive cancer puzzle seemingly correlated with cancer epidemiology in western populations as a result of excessive 2H loading from processed carbohydrate intake in place of natural fat consumption.
AB - The naturally occurring isotope of hydrogen (1H), deuterium (2H), could have an important biological role. Deuterium depleted water delays tumor progression in mice, dogs, cats and humans. Hydratase enzymes of the tricarboxylic acid (TCA) cycle control cell growth and deplete deuterium from redox cofactors, fatty acids and DNA, which undergo hydride ion and hydrogen atom transfer reactions. A model is proposed that emphasizes the terminal complex of mitochondrial electron transport chain reducing molecular oxygen to deuterium depleted water (DDW); this affects gluconeogenesis as well as fatty acid oxidation. In the former, the DDW is thought to diminish the deuteration of sugar-phosphates in the DNA backbone, helping to preserve stability of hydrogen bond networks, possibly protecting against aneuploidy and resisting strand breaks, occurring upon exposure to radiation and certain anticancer chemotherapeutics. DDW is proposed here to link cancer prevention and treatment using natural ketogenic diets, low deuterium drinking water, as well as DDW production as the mitochondrial downstream mechanism of targeted anti-cancer drugs such as Avastin and Glivec. The role of 2H in biology is a potential missing link to the elusive cancer puzzle seemingly correlated with cancer epidemiology in western populations as a result of excessive 2H loading from processed carbohydrate intake in place of natural fat consumption.
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U2 - 10.1016/j.mehy.2015.11.016
DO - 10.1016/j.mehy.2015.11.016
M3 - Article
C2 - 26826644
AN - SCOPUS:84955622266
SN - 0306-9877
VL - 87
SP - 69
EP - 74
JO - Medical Hypotheses
JF - Medical Hypotheses
ER -