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Zinc inhibition of pyruvate kinase of M-type isozyme

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Abstract

Inhibitory effect of Zn on the pyruvate kinase of M (muscle)-type isozyme was analyzed for the purpose of elucidating the cytotoxicity of Zn. Zn inhibited pyruvate kinase uncompetitively with respect to the substrate PEP, and competitively with respect to ADP. Quotient velocity plot calculated from the Zn-inhibition curves showed that Zn2+ as a ZnADP complex acted as competitive and uncompetitive inhibitors of the enzyme with respect to the substrate ADP and PEP, respectively: Zn2+ forms a ZnADP complex, which may bind to the ADP-binding site of the free enzyme with the Ki value of 1.4 μM causing competitive inhibition, or to the ADP-site of the enzyme-PEP complex with 2.6 μM resulting in uncompetitive inhibition. The inhibition of pyruvate kinase by Zn2+ may be responsible for the cytotoxicity of this metal by decreasing glycolytic flux.

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Authors and Affiliations

  1. Department of Biochemistry, Aichi Medical University School of Medicine, Yazako-karimata 1-1, Nagakute, Aichi, 480-1195, Japan

    Keiko Murakami & Masataka Yoshino

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  1. Keiko Murakami
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  2. Masataka Yoshino
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Correspondence to Masataka Yoshino.

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Murakami, K., Yoshino, M. Zinc inhibition of pyruvate kinase of M-type isozyme. Biometals 30, 335–340 (2017). https://doi.org/10.1007/s10534-017-0009-y

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