Low-molecular-weight thiols in thiol-disulfide exchange.
CONCLUSIONS
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) nonprotein thiols plays an essential role in maintaining the redox potential of the cell in balance.


BACKGROUND
While LMW thiols are central players in an extensive range of redox regulation/metabolism processes, not all organisms use the same thiol cofactors to this effect, as evidenced by the recent discovery of mycothiol (MSH) and bacillithiol (BSH) among different gram-positive bacteria.


RESULTS
LMW thiol-disulfide exchange processes and their cellular implications are often oversimplified, as only the biology of the free thiols and their symmetrical disulfides is considered. In bacteria under oxidative stress, especially where concentrations of different LMW thiols are comparable [e.g., BSH, coenzyme A (CoA), and cysteine (Cys) in many low-G+C gram-positive bacteria (Firmicutes)], mixed disulfides (e.g., CoASSB and CySSCoA) must surely be major thiol-redox metabolites that need to be taken into consideration.


CONCLUSIONS
There are many microorganisms whose LMW thiol-redox buffers have not yet been identified (either bioinformatically or experimentally). Many elements of BSH and MSH redox biochemistry remain to be explored. The fundamental biophysical properties, thiol pK(a) and redox potential, have not yet been determined, and the protein interactome in which the biothiols MSH and BSH are involved needs further exploration.
Department of Structural Biology, Vlaams Instituut voor Biotechnologie (VIB), Brussels, Belgium.
Koen
K
Van Laer
Chris J
CJ
Hamilton
Joris
J
Messens
D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism*
D004220:Disulfides; D013438:Sulfhydryl Compounds