Does arsenate inhibit glyceraldehyde 3-phosphate dehydrogenase?

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SUMMARY

Arsenate inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by mimicking phosphate, leading the enzyme to incorporate arsenate into glyceraldehyde 3-phosphate (G3P) instead of phosphate. This results in the formation of an unstable arsenate ester that rapidly hydrolyzes in aqueous solution, causing the enzyme to consume G3P without generating the intended product. Key literature includes Crane and Lipmann's 1952 study on the effects of arsenate on aerobic phosphorylation, which provides foundational insights into this biochemical interaction.

PREREQUISITES
  • Understanding of enzyme kinetics and inhibition mechanisms
  • Familiarity with the structure and function of glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
  • Knowledge of biochemical pathways involving aerobic phosphorylation
  • Basic principles of ester formation and hydrolysis in aqueous solutions
NEXT STEPS
  • Review the 1952 study by Crane and Lipmann on arsenate's effects on aerobic phosphorylation
  • Investigate the biochemical implications of arsenate as a phosphate analog
  • Explore the mechanisms of enzyme inhibition and substrate competition
  • Study the hydrolysis of arsenate esters in biochemical contexts
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Biochemists, molecular biologists, and researchers studying enzyme inhibition and metabolic pathways involving glyceraldehyde 3-phosphate dehydrogenase.

sameeralord
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I know it resembles a phosphate. Did a search it was very vague. Thanks :smile:
 
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Apparently arsenate "inhibits" GAPDH because arsenate is so similar to phosphate that the enzyme incorporates arsenate into G3P rather than phosphate. The arsenate ester that GAPDH creates, however, almost instantaneously hydrolyzes in aqueous solution, so the enzyme ends up consuming G3P without producing the product.

See Crane and Lipmann. 1952. The effect of arsenate on aerobic phosphorylation. J. Biol. Chem. 201: 235. http://www.jbc.org/content/201/1/235.full.pdf+html and the papers it references in the introduction.
 

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