Skeletal muscle glycogen phosphorylase is irreversibly inhibited by mercury: Molecular,cellular and kinetic aspects |
| |
Authors: | Ximing Xu,Cé cile Mathieu,Solè ne Emmanuelle Boitard,Julien Dairou,Jean-Marie Dupret,Onnik Agbulut,Fernando Rodrigues-Lima |
| |
Affiliation: | 1. Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC 4413, 75013 Paris, France;2. UFR des Sciences du Vivant, Univ Paris Diderot, 75013 Paris, France |
| |
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 (Hg2+) and organic (CH3Hg+) mercury (IC50 = 380 nM and kinact = 600 M−1 s−1 for Hg2+ 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 Mechanistic toxicology Mercury Glycogen metabolism |
本文献已被 ScienceDirect 等数据库收录! |
|