Understanding Hydrogen: Lessons to Be Learned from Physical Interactions between the Inert Gases and the Globin Superfamily

Abstract

Hydrogen gas (molecular hydrogen, H2) has significant effects in a range of organisms, from plants to humans. Many inert gases have been reported to have similar effects, and such responses may be most pronounced when cells are stressed. Xenon (Xe), for example, is a well-known anesthetic. The direct targets of these gases, in most cases, remain elusive. Myoglobin and hemoglobin are known for their roles in the transport of gases through coordinate interactions with metals (O2, NO, CO) and covalent modifications of thiols (NO, H2S) and amines (CO2). These are well exemplified in biotrophic reactions of NO with heme iron (to form iron nitrosyl heme) and cysteine (to form bioactive S-nitrosothiols) essential for tissue oxygenation. Here, we consider an alternative “third mode” of gas transport in what have been dubbed “Xenon pockets”, whereby inert gases may have functional effects. Many proteins have similar cavities, and possible effects include alterations in allosteric properties of proteins (potentially altering protein hydration). Here, it is suggested that similar to other inert gases, H2 also has biological effects by utilizing these protein structures. This ought to be investigated further, in a range of species, to determine if this is the mode of action of H2.