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Título:

Macromolecular crowding and bicarbonate enhance the hydrogen peroxide-induced inactivation of glyceraldehyde-3-phosphate dehydrogenase

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Autor:

Bloemen, Rebecca H. J.
Radi, Rafael
Davies, Michael J.
Fuentes-Lemus, Eduardo

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Artículo

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Palabras clave:

Glyceraldehyde-3-phosphate dehydrogenase
Hydrogen peroxide
Macromolecular crowding
Peroxymonocarbonate
Protein oxidation
Redox regulation

Descriptores:

ANIMALES
METABOLISMO
BICARBONATOS
GLICERALDEHÍDO-3-FOSFATO DESHIDROGENASAS
HUMANOS
FARMACOLOGÍA
PERÓXIDO DE HIDRÓGENO
OXIDACIÓN-REDUCCIÓN

Año de publicación:

2024

Contenido:

Resumen:

The active site Cys residue in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is sensitive to oxidation by hydrogen peroxide (H2O2), with this resulting in enzyme inactivation. This re-routes the carbon flux from glycolysis to the pentose phosphate pathway favoring the formation of NADPH and synthetic intermediates required for antioxidant defense and repair systems. Consequently, GAPDH inactivation serves as a redox switch for metabolic adaptation under conditions of oxidative stress. However, there is a major knowledge gap as to how GAPDH is efficiently oxidized and inactivated, when the increase in intracellular H2O2 is modest, and there is a high concentration of alternative (non-signaling) thiols and efficient peroxide removing systems. We have therefore explored whether GAPDH inactivation is enhanced by two factors of in vivo relevance: macromolecular crowding, an inherent property of biological environments, and the presence of bicarbonate, an abundant biological buffer. Bicarbonate is already known to modulate H2O2 metabolism via formation of peroxymonocarbonate. GAPDH activity was assessed in experiments with low doses of H2O2 under both dilute and crowded conditions (induced by inert high molecular mass polymers and small molecules), in both the absence and presence of 25 mM sodium bicarbonate. H2O2-induced inactivation of GAPDH was observed to be significantly enhanced under macromolecular crowding conditions, with bicarbonate having an additional effect. These data strongly suggest that these two factors are of major importance in redox switch mechanisms involving GAPDH (and possibly other thiol-dependent systems) within the cellular environment.

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Portland Press

EN:

Biochemical Journal. 2024;481(23):1855-1866

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Citación:

Bloemen R, Radi R, Davies M y otros. Macromolecular crowding and bicarbonate enhance the hydrogen peroxide-induced inactivation of glyceraldehyde-3-phosphate dehydrogenase. Biochemical Journal [en línea]. 2024;481(23):1855-1866

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Licencia Creative Commons Atribución (CC - By 4.0)

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