Interplay of carbon dioxide and peroxide metabolism in mammalian cells

Radí, Rafael

doi:10.1016/j.jbc.2022.102358

Cited by 37 publications

(34 citation statements)

References 183 publications

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“…Relays have been characterized for a limited number of yeast ( 23 , 24 ) and mammalian ( 25 , 26 ) proteins, but not for GAPDH. However, a possibly relevant factor, which has received little attention, is carbon dioxide ( 27 ). GAPDH functions in cells where the primary buffer is CO 2 /bicarbonate, and studies showing inactivation of cellular GAPDH by H 2 O 2 have usually been carried out in bicarbonate-containing media.…”

mentioning

confidence: 99%

Carbon dioxide/bicarbonate is required for sensitive inactivation of mammalian glyceraldehyde-3-phosphate dehydrogenase by hydrogen peroxide

Winterbourn

Peskin

Kleffmann

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox regulation. Here, we show that inactivation by hydrogen peroxide is strongly enhanced in the presence of carbon dioxide/bicarbonate. Inactivation of isolated mammalian GAPDH by H 2 O 2 increased with increasing bicarbonate concentration and was sevenfold faster in 25 mM (physiological) bicarbonate compared with bicarbonate-free buffer of the same pH. H 2 O 2 reacts reversibly with CO 2 to form a more reactive oxidant, peroxymonocarbonate (HCO 4 − ), which is most likely responsible for the enhanced inactivation. However, to account for the extent of enhancement, we propose that GAPDH must facilitate formation and/or targeting of HCO 4 − to promote its own inactivation. Inactivation of intracellular GAPDH was also strongly enhanced by bicarbonate: treatment of Jurkat cells with 20 µM H 2 O 2 in 25 mM bicarbonate buffer for 5 min caused almost complete GAPDH inactivation, but no loss of activity when bicarbonate was not present. H 2 O 2 -dependent GAPDH inhibition in bicarbonate buffer was observed even in the presence of reduced peroxiredoxin 2 and there was a significant increase in cellular glyceraldehyde-3-phosphate/dihydroxyacetone phosphate. Our results identify an unrecognized role for bicarbonate in enabling H 2 O 2 to influence inactivation of GAPDH and potentially reroute glucose metabolism from glycolysis to the pentose phosphate pathway and NAPDH production. They also demonstrate what could be wider interplay between CO 2 and H 2 O 2 in redox biology and the potential for variations in CO 2 metabolism to influence oxidative responses and redox signaling.

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mentioning

confidence: 99%

Carbon dioxide/bicarbonate is required for sensitive inactivation of mammalian glyceraldehyde-3-phosphate dehydrogenase by hydrogen peroxide

Winterbourn

Peskin

Kleffmann

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…CO2 is not inert in redox biology and directly modulates peroxide signaling and alters oxidation reactions. In addition, CO2 accelerates ROS production, redox signaling and subsequent oxidative stress 36 . As a modulator of cellular redox biology, CO2 also controls the expression of genes linked to redox and NO metabolism, thereby influencing oxidative and inflammatory processes 37 .…”

Section: Gravity and Human Respiration In Spacementioning

confidence: 99%

Gravity and Human Respiration: Biophysical Limitations in Mass Transport and Exchange in Space

Porterfield,

Dutta,

Tulodziecki

et al. 2024

Preprint

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A major requirement for humans is a breathable atmosphere. In microgravity, despite environmental life support systems regulating air exchange, astronauts complain about air quality, with elevated CO2-levels resulting in detrimental health and performance effects. We extend extant accounts of human respiration to include the role of gravity and buoyancy. Using computational fluid dynamics, we demonstrate that the absence of biothermal convection in microgravity reduces airflow around the human body. This impairs gas exchange by creating an environmental breathing deadspace in front of the face, leading to significant CO2-rebreathing, with implications for astronaut health and countermeasures. In 1g, increasing ambient air temperature can also reduce efficient respiratory exchange, resulting in breathing conditions equivalent to those in microgravity, with implications for treating respiratory disease on Earth.

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“…81 This reaction changes peroxynitrite's chemistry to that of a one-electron oxidant that produces mainly thiyl radicals as well as nitrating tyrosine residues in proteins. 82,83 There is no compelling evidence, however, that NO • is generated in human neutrophils. 29 Furthermore, nitration reactions were not observed when neutrophils phagocytosed either bacteria or beads coated with chemical traps for peroxynitrite.…”

Section: The Re Ac Tivit Y Of Superoxidementioning

confidence: 99%

“…It also reacts favorably with carbon dioxide ( k = 6 × 10 4 M −1 s −1 ) to form a transient intermediate that liberates nitrogen dioxide radical (

{NO}_{2}^{\cdot}

) and the carbonate radical (

{CO}_{3}^{- \cdot}

) 81 . This reaction changes peroxynitrite's chemistry to that of a one‐electron oxidant that produces mainly thiyl radicals as well as nitrating tyrosine residues in proteins 82,83 . There is no compelling evidence, however, that NO · is generated in human neutrophils 29 .…”

Section: The Reactivity Of Superoxidementioning

confidence: 99%

Superoxide: The enigmatic chemical chameleon in neutrophil biology

Ashby

Winterbourn

Dickerhof

2023

Immunological Reviews

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Three decades ago, our free radical research group in Ōtautahi Christchurch asked two rather straightforward questions: "What's so super about superoxide?", and "How do neutrophils use superoxide to kill bacteria?" 1-3 Neither question was particularly novel but they were at the heart of understanding the importance of the superoxide radical anion (O −⋅ 2 ) in oxidative stress and host defense. Naively, we thought that an answer to the first question would also satisfy the second question. We hoped that by probing how neutrophils use superoxide to kill ingested bacteria, we would reveal the toxic nature of superoxide. With these answers in hand, we could explain why the enzyme superoxide dismutase is needed to protect cells from oxidative stress. Our naiveté stretched to thinking that these questions would yield quick answers. But, in reality, the central question remains to this day: How does superoxide generation and removal fit into normal physiology? 4

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Interplay of carbon dioxide and peroxide metabolism in mammalian cells

Cited by 37 publications

References 183 publications

Carbon dioxide/bicarbonate is required for sensitive inactivation of mammalian glyceraldehyde-3-phosphate dehydrogenase by hydrogen peroxide

Carbon dioxide/bicarbonate is required for sensitive inactivation of mammalian glyceraldehyde-3-phosphate dehydrogenase by hydrogen peroxide

Gravity and Human Respiration: Biophysical Limitations in Mass Transport and Exchange in Space

Superoxide: The enigmatic chemical chameleon in neutrophil biology

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