Do small hydrogen-containing gas molecules support low deuterium in mitochondrial water?
- 1Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology
Abstract
Deuterium is a natural heavy isotope of hydrogen, containing a neutron as well as a proton, making it twice as heavy. Mitochondrial ATP synthase nanomotors are highly sensitive to deuterium, because it impedes the flow of protons through the nanomotors and causes the γ C-terminal helix to unwind. It appears that metabolic processes have evolved to devise ways to reduce the deuterium load in the mitochondria, primarily, we argue, by exploiting several small hydrogen-containing molecular gases. We propose that, when a gas is produced, deuterium, due to its extra weight, tends to stay behind in the aqueous medium, so the gas becomes deuterium-depleted. Furthermore, many of the enzymes that synthesize and/or metabolize these small gas molecules fractionate out deuterium by exploiting proton tunneling. We hypothesize that the gut microbes play a crucial role in producing deuterium-depleted gas molecules, such as hydrogen gas (H ₂ ), methane (CH ₄ ), ammonia (NH ₃ ), hydrogen sulfide (H ₂ S), trimethylamine (TMA), formaldehyde (HCHO), and methanethiol (CH ₃ SH). Gut microbial metabolism of TMA likely provides a low-deuterium source of one-carbon (1C) units to fuel the methylation pathway in the host. The glutamate-glutamine exchange that takes place between astrocytes and neurons plausibly capitalizes on NH ₃ to preferentially deliver ¹ H (protons) to neuronal mitochondria. Red blood cells actively import NH ₃ while the cation NH ₄ ⁺ is excreted in the urine, possibly as a strategy to fractionate out deuterium. In this paper, we investigate how small molecular hydrogen-containing gases are handled in metabolism, from a perspective that considers that these gases may serve a useful role in reducing the deuterium content in the mitochondria. Our hypothesis awaits validation by expert researchers who can perform appropriate experiments to test the hypothesis.
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BibTeX
@article{seneff2026small,
title = {{Do small hydrogen-containing gas molecules support low deuterium in mitochondrial water?}},
author = {Stephanie Seneff},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1933444},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933444/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Do small hydrogen-containing gas molecules support low deuterium in mitochondrial water?
AU - Stephanie Seneff
PY - 2026
DA - 2026/10/09
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1933444
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933444/full
AB - Deuterium is a natural heavy isotope of hydrogen, containing a neutron as well as a proton, making it twice as heavy. Mitochondrial ATP synthase nanomotors are highly sensitive to deuterium, because it impedes the flow of protons through the nanomotors and causes the γ C-terminal helix to unwind. It appears that metabolic processes have evolved to devise ways to reduce the deuterium load in the mitochondria, primarily, we argue, by exploiting several small hydrogen-containing molecular gases. We propose that, when a gas is produced, deuterium, due to its extra weight, tends to stay behind in the aqueous medium, so the gas becomes deuterium-depleted. Furthermore, many of the enzymes that synthesize and/or metabolize these small gas molecules fractionate out deuterium by exploiting proton tunneling. We hypothesize that the gut microbes play a crucial role in producing deuterium-depleted gas molecules, such as hydrogen gas (H ₂ ), methane (CH ₄ ), ammonia (NH ₃ ), hydrogen sulfide (H ₂ S), trimethylamine (TMA), formaldehyde (HCHO), and methanethiol (CH ₃ SH). Gut microbial metabolism of TMA likely provides a low-deuterium source of one-carbon (1C) units to fuel the methylation pathway in the host. The glutamate-glutamine exchange that takes place between astrocytes and neurons plausibly capitalizes on NH ₃ to preferentially deliver ¹ H (protons) to neuronal mitochondria. Red blood cells actively import NH ₃ while the cation NH ₄ ⁺ is excreted in the urine, possibly as a strategy to fractionate out deuterium. In this paper, we investigate how small molecular hydrogen-containing gases are handled in metabolism, from a perspective that considers that these gases may serve a useful role in reducing the deuterium content in the mitochondria. Our hypothesis awaits validation by expert researchers who can perform appropriate experiments to test the hypothesis.
SN - 1664-302X
ER -