Cardioprotective activity of a novel and potent competitive inhibitor of lactate dehydrogenase

Alexander Kotlyar, Antonio Randazzo, Norman Honbo, Zhu Qui Jin, Joel S. Karliner, Gary Cecchini

Research output: Contribution to journalArticlepeer-review

Abstract

Alkaline incubation of NADH results in the formation of a very potent inhibitor of lactate dehydrogenase. High resolution mass spectroscopy along with NMR characterization clearly showed that the inhibitor is derived from attachment of a glycolic acid moiety to the 4-position of the dihydronicotinamide ring of NADH. The very potent inhibitor is competitive with respect to NADH. The inhibitor added in submicromolar concentrations to cardiomyocytes protects them from damage caused by hypoxia/reoxygenation stress. In isolated mouse hearts, addition of the inhibitor results in a substantial reduction of myocardial infarct size caused by global ischemia/reperfusion injury.

Original languageEnglish
Pages (from-to)159-165
Number of pages7
JournalFEBS Letters
Volume584
Issue number1
DOIs
StatePublished - 4 Jan 2010

Keywords

  • Cardioprotection
  • Competitive inhibition
  • Enzyme kinetics
  • Lactate dehydrogenase
  • NADH derivative

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