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

doi:10.1016/j.febslet.2009.11.022

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

^*Corresponding author for this work

Biochemistry Molecular Biology

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	159-165
Number of pages	7
Journal	FEBS Letters
Volume	584
Issue number	1
DOIs	https://doi.org/10.1016/j.febslet.2009.11.022
State	Published - 4 Jan 2010

Keywords

Cardioprotection
Competitive inhibition
Enzyme kinetics
Lactate dehydrogenase
NADH derivative

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10.1016/j.febslet.2009.11.022

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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.",

keywords = "Cardioprotection, Competitive inhibition, Enzyme kinetics, Lactate dehydrogenase, NADH derivative",

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AU - Karliner, Joel S.

AU - Cecchini, Gary

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N2 - 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.

AB - 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.

KW - Cardioprotection

KW - Competitive inhibition

KW - Enzyme kinetics

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

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Keywords

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