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.

How Hydrogen (H2) Can Support Food Security: From Farm to Fork

“…However, considering the spatial and temporal distribution, and the kinetics of these highly reactive molecules, whether such reactions occur in vivo is questioned [41,42]. Alternative mechanisms of action involving the partial reduction in Fe 3+ moieties [43] and protein stabilisation [44] have been proposed, and whilst the modality of H 2 is currently a matter of academic debate, what is clear is that implementation of HRW and H 2 gas to post-harvest produce consistently demonstrates an increased resistance to ripening, senescence and spoilage in fruits, herbs and vegetables (Table 1). In addition to postharvest treatments, preharvest irrigation with HRW has also been demonstrated to protect natural produce against storage-related chilling injury [52].…”

Are Protein Cavities and Pockets Commonly Used by Redox Active Signalling Molecules?

“…As already mentioned, H 2 could be thrown into this mix [ 31 ]. There is no evidence that H 2 has an influence on the activity of proteins using such a mechanism.…”

“…There seems little doubt that inert gases such as Xe have an influence of protein activity [ 39 ], and therefore the activity of the cell, via the direct interaction of the gas molecules with proteins by taking advantage of the pockets and cavities that exist in protein structures. Other inert gases have similar biological effects and actions, including Ar, He, and Ne, while it has been suggested H 2 also acts in this way [ 31 ]. Certainly, for H 2 , much more work focused on this potential mechanism needs to be carried out, either to confirm that this is one of the modes of action of H 2 or to rule it out.…”

“…However, such mechanisms probably do not account for all the actions of H 2 . Several modes of action probably need to be considered to obtain a full understanding of what H 2 is doing in cells [ 31 ], including H 2 interactions with protein cavities.…”

“…With the knowledge that Xe can interact with proteins, it has recently been suggested that H 2 may mimic the action of other gases, i.e., it may interact with cavities and pockets in the structures of proteins [ 31 ]. Therefore, examining how inert gases act may provide an indication of how other molecules may have bioactivity.…”