Simultaneous generation of methane, carbon dioxide, and carbon monoxide from choline and ascorbic acid ‐ a defensive mechanism against reductive stress?

Abstract

Indirect evidence suggests that an abnormal increase in reducing power (reductive stress) may be associated with abnormal clinical states. We have recently proposed that under such conditions biomolecules with electrophilic methyl groups (EMGs) bound to positively charged nitrogen or sulfur moieties may act as electron acceptors and that this poising mechanism may entail the generation of methane gas. Here we report for the first time the generation of methane by rat liver mitochondria. We also report the formation of methane from choline in the presence of hydrogen peroxide, catalytic iron, and ascorbic acid. In this system, carbon monoxide and carbon dioxide are formed from the ascorbate molecule in parallel with methane generation. In view of these findings, we try to explain the essential role of biomolecules with EMG moiety. We hypothesize that this concerted reaction may be a defensive response to reductive stress and may provide the protection needed against redox imbalance in living systems.

Evidence for methane production by saprotrophic fungi

“…This is in accordance with the findings of Ghyczy et al 9,12 who demonstrated that endothelial cells from rat liver produced CH 4 when exposed to site-specific inhibitors of the ETC. It would seem that aerobic CH 4 formation is not only a result of chemical formation from dead biomass as previously shown by several studies 8,11 but might also have a physiological role in eukaryotic groups such as fungi, animals and plants.…”

“…Less well known are the findings of Ghyczy et al 9,12 who demonstrated that endothelial cells from rat liver produced CH 4 when exposed to site-specific inhibitors of the electron transport chain (ETC). A similar observation has been made for plant cell cultures grown under sterile and oxic conditions 13 .…”

A novel pathway of direct methane production and emission by eukaryotes including plants, animals and fungi: An overview

“…In vivo and in vitro studies have provided persuasive evidence of animal CH 4 production under stress conditions (Ghyczy et al, 2003(Ghyczy et al, , 2008aTuboly et al, 2013a;Tuboly et al, 2013b). Sodium azide (NaN 3 ) administration is a widely used method to cause mitochondrial dysfunction (Ghyczy et Fungous Methionine a Postulated reaction schemes for CH 4 production in plants and fungi (reaction ①) as well as animals (reaction ②).…”

“…Moreover, NaN 3 treatment causes reactive oxygen species (ROS) production (Ji et al, 2011;Tuboly et al, 2013b). Hypoxic mitochondrial CH 4 production was found in rats (Ghyczy et al, 2003;Tuboly et al, 2013b), and such CH 4 -generating capacity has proved to be independent of the methanogenic flora because it persists after antibiotic treatment targeting the gastrointestinal methanogenic archaea. CH 4 production can occur not only in rat mitochondria but also in bovine endothelial cells under hypoxic conditions (Ghyczy et al, 2008a).…”

“…NaN 3 administration is widely used in studies to cause reductive damage in animals (Ghyczy et al, 2008a;Tuboly et al, 2013b). EMGs bound to positively charged nitrogen or sulphur moieties serve as electron acceptors when methyl groups adjacent to an N or S atom are electron-deficient and their reactions thus entail CH 4 formation (Ghyczy and Boros, 2001;Ghyczy et al, 2003). In this sequence, hypoxia maintains a high mitochondrial NADH:NAD þ radio, and a nucleophilic hydride ion from electron donors (e.g.…”