Zinc inhibition of pyruvate kinase of M-type isozyme

• Published in: Biometals 2017-06, Vol.30 (3), p.335-340
• Main Authors: Murakami, Keiko, Yoshino, Masataka
• Format: Article
• Language: English
• Subjects: Animals; Beryllium; Binding sites; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cytotoxicity; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Enzymes; Glycolysis; Isoenzymes - antagonists & inhibitors; Isoenzymes - classification; Isoenzymes - metabolism; Kinases; Life Sciences; Medicine/Public Health; Microbiology; Muscle, Skeletal - enzymology; Pharmacology/Toxicology; Plant Physiology; Pyruvate kinase; Pyruvate Kinase - antagonists & inhibitors; Pyruvate Kinase - classification; Pyruvate Kinase - metabolism; Pyruvic acid; Rabbits; Structure-Activity Relationship; Substrate inhibition; Toxicity; Velocity; Zinc; Zinc - pharmacology
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-017-0009-y

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 Zn 2+ as a ZnADP complex acted as competitive and uncompetitive inhibitors of the enzyme with respect to the substrate ADP and PEP, respectively: Zn 2+ forms a ZnADP complex, which may bind to the ADP-binding site of the free enzyme with the K i 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 Zn 2+ may be responsible for the cytotoxicity of this metal by decreasing glycolytic flux.