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Publication

Low molecular weight thiols in thiol disulfide exchange

Journal Contribution - Journal Article

Significance: Oxidative stress is widely invoked in inflammation, aging and complex diseases. To avoid unwanted oxidations, the redox environment of cellular compartments needs to be tightly controlled. The complementary action of oxidoreductases and of high concentrations of low molecular weight (LMW) non-protein thiols play an essential role in maintaining the redox potential of the cell in balance.
Recent Advances: Whilst LMW thiols are central players in an extensive range of redox regulation/metabolism processes not all organisms use the same thiol cofactor(s) to this effect, as evidenced by the recent discovery of mycothiol and bacillithiol amongst different Gram-positive bacteria.
Critical Issues: LMW thiol-disulfide exchange processes and their cellular implications are often oversimplified as only the biology of the free thiols and their symmetrical disulfides are considered. In bacteria under oxidative stress, especially where concentrations of different LMW thiols are comparable (eg, bacillithiol (BSH), Coenzyme A (CoA), and cysteine (Cys) in many low G+C Gram positive bacteria (Firmicutes)), mixed disulfides (eg. CoASSB, CySSCoA, etc) must surely be major thiol redox metabolites that need to be taken into consideration.
Future Directions: There are many microorganisms whose low molecular weight thiol redox buffer(s) have not yet been identified (either bioinformatically or experimentally). Many elements of BSH and mycothiol (MSH) redox biochemistry remain to be explored. The fundamental biophysical properties, thiol pKa and redox potential, have not yet been determined, and the protein interactome in which the biothiols MSH and BSH are involved needs further exploration.
Journal: Antioxid Redox Signal
ISSN: 1523-0864
Issue: 13
Volume: 18
Pages: 1642-1653
Publication year:2013
Keywords:Disulfides, Kinetics, Molecular Weight, Oxidation-Reduction, Oxidative Stress, Sulfhydryl Compounds, Journal Article, Research Support, Non-U.S. Gov't, Review