Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle

Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Medical Hypotheses Elsevier

Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Ltd
ISSN
0306-9877
eISSN
1532-2777
DOI
10.1016/j.mehy.2015.11.016
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Medical HypothesesElsevier

Published: Feb 1, 2016

References

  • Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism?
    Boros, L.G.; Lee, P.W.; Brandes, J.L.
  • Metabolic targeted therapy of cancer: current tracer technologies and future drug design strategies in the old metabolic network
    Boros, L.G.
  • Intramolecular deuterium distributions reveal disequilibrium of chloroplast phosphoglucose isomerase
    Schleucher, J.; Vanderveer, P.; Markley
  • Natural deuterium distribution in fatty acids isolated from peanut seed oil: a site-specific study by quantitative 2 H NMR spectroscopy
    Duan, J.R.; Billault, I.; Mabon, F.; Robins, R.J.
  • Natural deuterium distribution in long-chain fatty acids is nonstatistical: a site-specific study by quantitative 2 H NMR spectroscopy
    Billault, I.; Guiet, S.; Mabon, F.; Robins, R.J.
  • Characterization of a murine high-affinity thiamine transporter, Slc19a2
    Fleming, J.C.
  • Metabolic profile and quantification of deoxyribose synthesis pathways in HepG2 cells
    Centelles, J.J.

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