PMID: 4125Apr 8, 1976

Alkylation of cysteinyl residues of pig heart NAD-specific isocitrate dehydrogenase by iodoacetate

Biochimica Et Biophysica Acta
L Mauck, R F Colman

Abstract

Pig heart NAD-specific isocitrate dehydrogenase is inactivated by reaction with iodoacetate at pH 6.0. Loss of activity can be attributed to the formation of 1-2 mol of carboxymethyl-cysteine per peptide chain. The rate of inactivation is markedly decreased by the combined addition of Mn2+ and isocitrate, but not by alpha-ketoglutarate, the coenzyme NAD or the allosteric activator ADP. The substrate concentration dependence of the decreased rate of inactivation yields a dissociation constant of 1.6 mM for the enzyme-manganous-dibasic isocitrate complex, a value that is 50 times higher than the Km for this substrate. This result suggests that in protecting the enzyme against iodoacetate, isocitrate may bind to a region distinct from the catalytic site. Isocitrate and Mn2+ also prevent thermal denaturation, with an affinity for the enzyme close to that observed for the iodoacetate-sensitive site. The alkylatable cysteine residues may contribute to a manganous-isocitrate binding site which is responsible for stabilizing an active conformation of the enzyme.

References

Oct 18, 1951·The New England Journal of Medicine·H R VIETS

Related Concepts

Metazoa
Cysteine Hydrochloride
Enzyme Activation
Hydrogen-Ion Concentration
Iodoacetic Acids
Isocitrate Dehydrogenase-I
Manganese
Myocardium
NADH
Plasma Protein Binding Capacity

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