[radical886]

I have a couple of questions on the oxidation of GSH, hoping someone can help answer or lead me in the direction of some papers to read. I'm a researcher in biomedical science, so although I understand biochemistry, its not exactly my forte.

GSH is often said to be oxidised to GSSG. The thiol-disulphide ratio is an important indicator of the redox status of the cell etc Then I came across this paper in Angew Chem recently. "On the Reactions of Thiols, Sulfenic Acids, and Sulfinic Acids with Hydrogen Peroxide." https://www.ncbi.nlm.nih.gov/pubmed/27933690

They show that GSH reacts with peroxide to give a sulfenic acid, which then further oxidises into sulfinic and sulfonic acids. More surprisingly, in the text they speak of this as its an expected reaction. The disulphide form is not mentioned at all.

Does anyone know if there are rules on the oxidation of GSH by various free radicals/oxidants, or if they know of a review/original paper which lays this out?

Is it that the GSSG form comes up only during the presence of enzyme catalysed oxidation of GSH (for example I know that GSH peroxidase catalyses the conversion of GSH and peroxide into GSSG and water)? And in the absence of enzymes, the direct reaction of GSH with oxidants/free radicals gives the sulfenic form?

It seems rather confusing, as it looks like GSSG is not the 'sole' oxidation product of GSH as I once thought. Any help would be much appreciated!

[Babcock_Hall]

Your question seems broad upon first examination.  It might be worthwhile to start out by separating typical reactions in the cell versus those found in the test tube.  I am not sure how physiologically relevant the conditions in the paper you cited are (which is not to say that the work is flawed).  For example, glutathione peroxidase reacts hydrogen peroxide with two molecules of GSH to produce GSSG.  GSSG is reduced using NADPH by glutathione reductase.

With respect to non enzymatic chemistry, supposed one molecule thiol is oxidized to a sulfenic acid.  It is possible that the fate of the sulfenic acid is controlled by the concentrations of thiol versus hydrogen peroxide and the two associated rate constants.  If the concentration of thiol is large, one obtains a disulfide because the thiol captures the sulfenic acid.  If the concentration of peroxide is large, one obtains the sulfinic acid.

I found a review by Mauro Lo Conte and Kate S. Carroll in Oxidative Stress and Redox Regulation called "The chemistry of thiol oxidation and detection."  There might be some good information there.

[radical886]

Hi, thank you for that answer. It is clear to me that I need to consider enzymatic (1) vs non-enzymatic oxidation of GSH (2), and non-enzymatic can be split further into oxidation in excess of GSH (2a), or an excess of oxidant (2b). Based on this framework, it looks like under 1 and 2a, GSSG is the major/sole product. Under 2b, you get sulfenic acids and further oxidation products. There might be some exceptions, but this works for me and gives some sort of clarity in my mind. Thanks!