The role of formate in combatting oxidative stress

Abstract

The interaction of keto-acids with reactive oxygen species (ROS) is known to produce the corresponding carboxylic acid with the concomitant formation of CO2. Formate is liberated when the keto-acid glyoxylate neutralizes ROS. Here we report on how formate is involved in combating oxidative stress in the nutritionally-versatile Pseudomonas fluorescens. When the microbe was subjected to hydrogen peroxide (H2O2), the levels of formate were 8 and two-fold higher in the spent fluid and the soluble cell-free extracts obtained in the stressed cultures compared to the controls respectively. Formate was subsequently utilized as a reducing force to generate NADPH and succinate. The former is mediated by formate dehydrogenase (FDH-NADP), whose activity was enhanced in the stressed cells. Fumarate reductase that catalyzes the conversion of fumarate into succinate was also markedly increased in the stressed cells. These enzymes were modulated by H2O2. While the stressed whole cells produced copious amounts of formate in the presence of glycine, the cell-free extracts synthesized ATP and succinate from formate. Although the exact role of formate in anti-oxidative defence has to await further investigation, the data in this report suggest that this carboxylic acid may be a potent reductive force against oxidative stress.

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Notes

  1. 1.

    (These values were compared to the formate levels in the respective control experiments where the cells were omitted respectively).

  2. 2.

    These are compared to the formate values in the reaction mixture in the control and stressed bands at time 0.

  3. 3.

    These are relative to succinate levels in the control and stress reaction bands at time 0 respectively.

  4. 4.

    These values are relative to the respective metabolite levels in the reaction mixtures at time 0.

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Acknowledgments

This work was supported by Laurentian University and Northern Ontario Heritage Fund Corporation. Sean C. Thomas is a recipient of the Natural Sciences and Engineering Research Council Post Graduate Scholarship-Masters. Azhar Alhasawi is a recipient of a doctoral scholarship from the Ministry of Higher Education of Saudi Arabia.

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Correspondence to Vasu D. Appanna.

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Thomas, S.C., Alhasawi, A., Auger, C. et al. The role of formate in combatting oxidative stress. Antonie van Leeuwenhoek 109, 263–271 (2016). https://doi.org/10.1007/s10482-015-0629-6

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Keywords

  • Formate metabolism
  • Pseudomonas fluorescens
  • Ketoacids
  • Glyoxylate
  • Formate dehydrogenase
  • Fumarate reductase- formate dependent
  • Isocitrate lyase