The Interactions of Bacillithiol with Carbonyl Containing Metabolites

Rodrigues, Dominic (2017) The Interactions of Bacillithiol with Carbonyl Containing Metabolites. Doctoral thesis, University of East Anglia.

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Bacillithiol (BSH) is a recently discovered low molecular weight (LMW) thiol found amongst several Gram-positive bacteria including Bacillus anthracis, Staphylococcus aureus and Bacillus subtilis. It plays a fundamental role in the redox processes within the cell, in addition to many other functions including the detoxification of electrophiles such as methylglyoxal (MG). MG is a reactive dicarbonyl produced as a by-product of glycolysis. It is found to be toxic to the cell as it is capable of modifying macromolecules such as proteins and DNA causing loss of biological activity. The previously established glutathione-dependent glyoxalase pathway comprises of the glyoxalase I and glyoxalase II enzyme, which are found to serve as a major mechanism for the detoxification of MG amongst eukaryotes. There is speculation that BSH follows through this same pathway.
Herein, the BSH-dependent glyoxalase pathway in B. subtilis is fully explored. The studies have shown a reaction between BSH and MG to occur spontaneously both in vitro and in vivo. Furthermore, these observations, have lead onto the discovery that, for the first time, BSH has shown to react with other metabolites in glycolysis. These include dihydroxyacetone phosphate, D-glyceraldehyde 3-phosphate and pyruvate. In each case they form a hemithioacetal (HTA). As a result, potentially significant concentrations of BSH may be sequestered in these ‘unknown thiol reservoirs’ which were not previously known to exist in the cell. Essentially, this raises questions regarding the true overall concentration of intracellular BSH.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Bruce Beckett
Date Deposited: 20 Jul 2018 08:27
Last Modified: 20 Jul 2018 08:27

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