Publishing venue: 4th International Conference on Deuterium Depletion (Deupletion)
Author(s) and Title: Boros LG, Somlyai G. Metabolic protonation of matrix water entails deuterium depletion for mitochondrial health via Eigen and Zundel type hydronium complex formation: medical implications
How It’s Depleted:
Hydronium is the aqueous cation (H3O+) produced by the protonation of bulk water (H2O) and it is the positive ion present when protons, i.e. positively charged hydrogen ions (H+) are added to surrounding water molecules (1). The mitochondrial matrix is such highly protonated compartment from food deriving excess protons at ATPase proton discharge sites that it must first form hydronium cations to transiently anchor in and physically alter as many as four surrounding metabolic water shells. Although positively charged hydrogen ions in excess readily transform bulk metabolic water to hydronium-based Eigen- (H3O+) and Zundel-type (H5O2+) cation complexes, the vastly altered proton solvation, tunneling and mobility patterns of the highly-structured matrix water shell (2) have not been interpreted in connection with the morphology and function of mitochondria. Such interpretations are timely because several studies found two to four hydronium solving water layers that differ from bulk water (3-6) due to the almost doubled values for hydrogen bond enthalpies (strengths) at protonated sites. The Eigen and Zundel type structuring of matrix water provide new insights into the fundamental physical force behind continuous proton harvesting and oxygen consumption during metabolic water formation and its rapid recycling from less protonated solvation shells by hydratases of the tricarboxylic acid cycle. While previous extensive molecular-dynamics simulations have successfully been applied to determine hydrogen-bond strengths in bulk (liquid) water, more recent simulations performed for protonated water open new doorways to medical interpretations of mitochondrial proton harvesting, water producing, structuring and recycling functions, where only structured water layers are present as revealed by inelastic incoherent neutron scattering studies (2). As proton tunneling and mobility patterns in hydrogen-bonding water solvation shells are greatly limited by both hydronium and deuteron substitutions (5, 6), these cations readily alter viscosity and structure of interfacial hydration shells that critically influence mitochondrial ATP synthesis, hence cellular health (7). The linear correlation of hydrogen bond strengths with lengths suggests that the enthalpy (strength) of an Eigen type hydrogen bond is 18.4 kJ/mol (6), as compared with only 10.6 kJ/mol in bulk water, based on Raman measurements (8, 9). This talk discusses proton mobility in matrix water that is intimately connected with the surrounding hydrogen bonding pattern with emphasis on the excessive kinetic isotope effect of deuterium (5) for broad translational and medical interpretations.
Quantum destabilization of protons during metabolic water formation and restructuring in mitochondria, a process compromised by Deuterium (10, 11) in nano-confinements of the matrix, is a crucial novel approach in medicinal deutenomics for advancing clinical, translational and nutritional sciences.
Literature:
1.) van der Spoel, D.; van Maaren, P. J.; Larsson, P.; Timneanu, N. J. Phys. Chem. B 2006, 110, 4393-4398.
2.) Stuart, V. Inelastic incoherent neutron scattering studies of water interacting with biological macromolecules. J. Am. Chem. Soc.20021244565-569. https://doi.org/10.1021/ja016277w
3.) Special Issue on Proton Solvation and Proton Mobility. Agmon, N., Gutman, M., Eds. Isr. J. Chem. 1999, 39 (3/4).
4.) Voth, G. A. Acc. Chem. Res. 2006, 39, 143-150.
5.) Drechsel‐Grau, C., Marx D. https://doi.org/10.1002/anie.201405989
6.) Markovitch, O., Agmon, N. J. Phys. Chem. https://doi.org/10.1021/jp068960g
7.) Sommer, A.P., Haddad, M., Fecht J. https://www.nature.com/articles/srep12029
8.) Agmon, N. J. Chim. Phys. Phys.sChim. Biol. 1996, 93, 1714-1736.
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11.) Buddha RS, et al, J. Phys. Chem. Letters (2019). https://doi.org/10.1021/acs.jpclett.9b01835
Key Words:
deuterium depletion, mitochondrial matrix metabolic water, deuterium-depleted water, NADPH, Eigen cation, Zundel cation, proton tunneling, mitochondria, hydronium, structured water, interfacial water, quantum destabilization of water, cristae, crypts, nano-confinements
Author Information:
Correspondence and requests for materials should be addressed to L.G.B. boros.laszlo@yahoo.com (USA)
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