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A Short History of Hydrogen Sulfide

From the sewers of Paris to physiological messenger

Roger P. Smith

New Biological Roles

Inhibition of cytochrome c oxidase results in a decrease in oxidative phosphorylation (the metabolic pathway that produces ATP). This in turn lowers the metabolic rate and body temperature in mice. These phenomena accompany states of suspended animation. When mice were exposed to hydrogen sulfide at concentrations of 80 ppm, dramatic effects were observed in the first 5 minutes. By 6 hours, their metabolic rate had dropped by 90 percent and body temperature to 2 degrees Celsius above ambient temperature. When the mice were then returned to room air, the metabolic rate and temperature returned to normal with no detectable behavioral or functional deficits. As already noted, lethal levels for hydrogen sulfide in mice are much higher than for dogs, but this state in mice must also occur over a fairly narrow range of concentrations.

Finally, and most astonishingly of all, experimental evidence contributed in 2008 indicates that like carbon monoxide and nitric oxide, hydrogen sulfide is an important signaling molecule in biology, and it may find a role in medicine. It is physiologically generated in mice by cystathionine γ-lyase, and genetic deletion of that enzyme markedly reduces hydrogen sulfide levels in the serum, heart, aorta and other tissues. Mutant mice lacking the enzyme have marked hypertension and diminished endothelium-dependent vasorelaxation, consistent with an important vasodilator role for hydrogen sulfide. The enzyme is physiologically activated by the calcium-binding protein calmodulin, which is a mechanism for hydrogen sulfide formation in response to vascular activation. Thus, hydrogen sulfide appears to be a physiologic vasodilator and regulator of blood pressure. Its relative contribution vis-à-vis the similar nitric oxide is not yet clear.

What a strange and wondrous journey this odiferous and violently toxic chemical, associated with the excrement of humanity, has led us on for five centuries. It’s a history that could fill a book, one that covers a vast range of territory, from the search to determine the cause of workplace injuries to fascinating discoveries about how hydrogen sulfide interacts with chemoreceptors in the body. And for all the false leads, in the end it may yet turn out to have some useful applications in medicine—even if only a new Viagra.

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