Skeletal muscle glycogen phosphorylase is irreversibly inhibited by mercury: molecular, cellular and kinetic aspects

FEBS Lett. 2014 Jan 3;588(1):138-42. doi: 10.1016/j.febslet.2013.11.021. Epub 2013 Nov 21.

Abstract

Muscle glycogen phosphorylase (GP) plays an important role in muscle functions. Mercury has toxic effects in skeletal muscle leading to muscle weakness or cramps. However, the mechanisms underlying these toxic effects are poorly understood. We report that GP is irreversibly inhibited by inorganic (Hg(2+)) and organic (CH3Hg(+)) mercury (IC50=380 nM and kinact=600 M(-1) s(-1) for Hg(2+) and IC50=43 μM and kinact=13 M(-1) s(-1) for CH3Hg(+)) through reaction of these compounds with cysteine residues of the enzyme. Our data suggest that the irreversible inhibition of GP could represent one of the mechanisms that contribute to mercury-dependent muscle toxicity.

Keywords: Enzyme inhibition; Glycogen metabolism; Mechanistic toxicology; Mercury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cysteine / metabolism
  • Dose-Response Relationship, Drug
  • Glycogen Phosphorylase / antagonists & inhibitors*
  • Glycogen Phosphorylase / metabolism*
  • Kinetics
  • Male
  • Mercuric Chloride / toxicity
  • Mercury / toxicity*
  • Methylmercury Compounds / toxicity
  • Mice
  • Muscle, Skeletal / enzymology*
  • Time Factors

Substances

  • Methylmercury Compounds
  • Mercuric Chloride
  • Glycogen Phosphorylase
  • Mercury
  • Cysteine