Rapid and irreversible inhibition of creatine kinase by peroxynitrite

FEBS Letters

Kalyanaraman, B.¹  Konorev, Eugene A.¹  Hogg, Neil¹ 

[1] Biophysics Research Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, P.O. Box 26509, Milwaukee, WI 53226-0509, USA

关键词: Peroxynitrite;    Nitric oxide;    Superoxide;    Creatine kinase;    CK;    creatine kinase;    ⋅NO;    nitric oxide;    GSH;    glutathione;    reduced form;    GSSG;    glutathione;    oxidized form;    SNN;    spermine NONOate;    SIN;    1;    3-morpholino-sydnonimine;    XO;    xanthine oxidase;    SOD;    superoxide dismutase;    PCr;    phosphocreatine;    GSNO;    S-nitrosoglutathione;    DTNB;    5;    5′-dithiobis-(2-nitrobenzoic acid);    BSA;    bovine serum albumin;    iNOS;    inducible ⋅NO synthase;   

DOI  :  10.1016/S0014-5793(98)00413-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We examined the ability of peroxynitrite and other ^⋅NO-derived oxidants to inhibit creatine kinase (CK). Peroxynitrite potently inhibited CK activity and depleted protein thiols. The rate constant for this reaction was 8.85×10⁵ M⁻¹ s⁻¹. Glutathione did not reactivate CK activity nor did it regenerate protein thiol content. In contrast, glutathione reactivated CK, and regenerated protein thiols, after inhibition by either ^⋅NO or oxidized glutathione (GSSG). Peroxynitrite did not irreversibly inhibit CK after it had been treated with GSSG to block protein thiols. We conclude that thiol oxidation is a critical event leading to inactivation of CK by peroxynitrite.

【 授权许可】

Unknown