Journal of Biological Chemistry
Volume 279, Issue 7, 13 February 2004, Pages 5257-5262
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Protein Structure and Folding
A Major Fraction of Endoplasmic Reticulum-located Glutathione Is Present as Mixed Disulfides with Protein*

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The tripeptide glutathione is the most abundant thiol/disulfide component of the eukaryotic cell and is known to be present in the endoplasmic reticulum lumen. Accordingly, the thiol/disulfide redox status of the endoplasmic reticulum lumen is defined by the status of glutathione, and it has been assumed that reduced and oxidized glutathione form the principal redox buffer. We have determined the distribution of glutathione between different chemical states in rat liver microsomes by labeling with the thiol-specific label monobromobimane and subsequent separation by reversed phase high performance liquid chromatography. More than half of the microsomal glutathione was found to be present in mixed disulfides with protein, the remainder being distributed between the reduced and oxidized forms of glutathione in the ratio of 3:1. The high proportion of the total population of glutathione that was found to be in mixed disulfides with protein has significant implications for the redox state and buffering capacity of the endoplasmic reticulum and, hence, for the formation of disulfide bonds in vivo.

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*

This work was supported by the Biotechnology and Biological Sciences Research Council through the award of a studentship (to R. B.) and by European Union Contract B10 4 CT 960436. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Current address: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.

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Current address: Dept. of Biochemistry, FIN-90014 University of Oulu, Finland.

Current address: Dept. of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.