The role of formate in combatting oxidative stress

Abstract

As all aerobic organisms are exposed to oxidative stress, they are known to devise intricate mechanisms to counter reactive oxygen species (ROS). Metabolic networks contributing to the production of ketoacids are prominent in alleviating the oxidative burden. When glyoxylate detoxifies ROS, formate is the principal by-product generated.In this study the contribution of formate in enabling the survival of the microbe Pseudomonas fluorescens challenged by hydrogen peroxide (H2O2) has been elucidated.When grown in the presence of H2O2 (stressed culture), the levels of formate were higher in the spent fluid and the soluble cell-free extracts compared to the controls. Formate was subsequently utilized as a reducing factor to produce NADPH and succinate. The former is mediated by formate dehydrogenase (FDH-NADP), whose activity was enhanced in the stressed cells. Fumarate reductase (FRD) that catalyzes the conversion of fumarate into succinate was also markedly increased in the stressed cells. Metabolic adaptation is a pivotal tool in combatting oxidative stress. Formate, a by-product of glyoxylate-mediated detoxification of ROS is recuperated as a potent reductive fuel. It is becoming quite evident that this simple metabolite has other biological roles that have not been fully appreciated.

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

“…Furthermore, the existing study established that oxidative stress affects metabolism via multiple mechanisms (Noctor, Lelarge‐Trouverie, & Mhamdi, ). Our results suggest that the MA‐induced oxidative stress depletes the release of formate, as previous study demonstrated that cells release formate when encountering oxidative stress (Jong, Azuma, & Schaffer, ; Thomas, Alhasawi, Auger, Omri, & Appanna, ). Furthermore, the significant elevations in acetoacetate observed in the medium‐dose group suggest MA induces lipid peroxidation (Jain, Kannan, & Lim, ).…”

H<sub>2</sub>O<sub>2</sub> modulates the energetic metabolism of the cloud microbiome

“…Second, it could reveal the impact of H 2 O 2 on the C1 metabolism; it is known that C1 compounds can be transformed by cloud microorganisms (Husàrovà et al, 2011;Vaitilingom et al, 2010Vaitilingom et al, , 2011Vaitilingom et al, , 2013. In addition, Thomas et al (2016) report the overproduction of formate in a strain of Pseudomonas fluorescens exposed to H 2 O 2 . Indeed, formate contributes to the anti-oxidant strategy of this bacterium to supply NADH, which is known to be decreased under oxidative conditions.…”

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“…; Thomas et al . ). Combined with observations that ketoacids can undergo non‐enzymatic decarboxylation in the presence of oxidizing agents (Bunton ; Mallet and Sun ; Mailloux et al .…”

“…; Thomas et al . ). Indeed, there are numerous, known and likely undiscovered, ketoacids that can be generated through the diverse metabolic pathways in prokaryotes.…”

“…This single carbon carboxylic acid is a potent inhibitor of cytochrome C oxidase, an attribute that would impede oxidative phosphorylation, a process responsible for substantial formation of ROS (Haritos and Dojchinov ; Thomas et al . ). Formate can also contribute to the production of NADPH via the enzyme formate dehydrogenase.…”