The central role of glutathione in the pathophysiology of human diseases

R. Franco, O. J. Schoneveld, A. Pappa, M. I. Panayiotidis

Research output: Contribution to journalReview article

312 Scopus citations

Abstract

Reduced glutathione (L - glutamyl-L-cysteinyl-glycine, GSH) is the prevalent low-molecular-weight thiol in mammalian cells. It is formed in a two-step enzymatic process including, first, the formation of -glutamylcysteine from glutamate and cysteine, by the activity of the -glutamylcysteine synthetase; and second, the formation of GSH by the activity of GSH sythetase which uses -glutamylcysteine and glycine as substrates. While its synthesis and metabolism occur intracellularly, its catabolism occurs extracellularly by a series of enzymatic and plasma membrane transport steps. Glutathione metabolism and transport participates in many cellular reactions including: antioxidant defense of the cell, drug detoxification and cell signaling (involved in the regulation of gene expression, apoptosis and cell proliferation). Alterations in its concentration have also been demonstrated to be a common feature of many pathological conditions including diabetes, cancer, AIDS, neurodegenerative and liver diseases. Additionally, GSH catabolism has been recently reported to modulate redox-sensitive components of signal transduction cascades. In this manuscript, we review the current state of knowledge on the role of GSH in the pathogenesis of human diseases with the aim to underscore its relevance in translational research for future therapeutic treatment design.

Original languageEnglish (US)
Pages (from-to)234-258
Number of pages25
JournalArchives of Physiology and Biochemistry
Volume113
Issue number4-5
DOIs
StatePublished - Oct 2007

Keywords

  • Apoptosis
  • Free radicals
  • GSH
  • Glutathiolation
  • Glutathione S-transferases
  • Glutathione depletion
  • Glutathione peroxidase
  • Glutathione reductase
  • Glutathionylation
  • Human diseases
  • Human disorders
  • Nitrosylation
  • Oxidative stress
  • ROS
  • Thiols

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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