Schistosoma mansoni: Inhibition of glucosephosphate isomerase and glycolysis by sugar phosphates

Theresa A. Shapiro, Paul Talalay

Research output: Contribution to journalArticlepeer-review

Abstract

Glucosephosphate isomerase (EC 5.3.1.9) of Schistosoma mansoni is inhibited competitively by a number of tetrose, pentose, and hexose phosphates with inhibitor constant (Ki) values in the range of 0.5 to 400 μM. The most potent inhibitor is 5-phospho-d-arabinonate which resembles the cis-enediolate transition state intermediate of the reaction. These analogs were also found to be effective inhibitors of the production of lactate from glucose by suitably supplemented worm homogenates. The rank order of potency of inhibition of glycolysis was inversely related to the magnitudes of the Ki values for glucosephosphate isomerase. These Ki values were similar to those previously reported for mammalian glucosephosphate isomerase, suggesting similarities in the steric and electronic characteristics of the active sites of these isofunctional enzymes. This conclusion was further supported by the observed pH dependence of the inhibition by 5-phospho-d-arabinonate. Although glucosephosphate isomerase is not a rate-limiting enzyme of glycolysis, in the conventional sense, its selective inhibition could be of chemotherapeutic importance, in part because of the accumulation in glycolyzing systems of glucose 6-phosphate which is a potent feedback inhibitor of hexokinase.

Original languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalExperimental Parasitology
Volume54
Issue number2
DOIs
StatePublished - Oct 1982

Keywords

  • 2-deoxy-d-glucose 6-phosphate
  • 5-phospho-d-arabinonate
  • 6-phosphogluconate
  • Glucosamine 6-phosphate
  • Glucosephosphate isomerase (EC 5.3.1.9)
  • Glycolysis
  • Inhibition, competitive
  • Schistosoma mansoni, adult
  • Trematode, parasitic
  • d-arabinose 5-phosphate
  • d-erythrose 4-phosphate
  • d-sorbitol 6-phosphate

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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