Glutathione chemical activity

Lane, H.W., Strength, R., Johnson, J., and White, M. 1991. Effect of chemical form of selenium on tissue glutathione peroxidase activity in developing rats. J. Nutr. 121, 80-86. 

Mugesh, G and HB Singh (2000). Synthetic organoselenium compounds as antioxidants Glutathione peroxidase activity. Chemical Society Reviews, 29,347-357. 

The reversibility of QM adducts also creates numerous challenges. For example, measuring the full burden of DNA alkylation by a QM can be obscured by the loss of its labile products during or before chemical identification can be completed. Results from a deoxynucleotide model system indicated that only a small fraction of the possible adducts could be measured after the interval required for analysis of DNA. Perhaps the kinetic products of QMs also contribute to the cellular activity of these intermediates although this has yet to be explored. QM equivalents can be envisioned to migrate from one reversible nucleophile such as the N1 of adenine in such cofactors as ATP to another until quenched by a compound such as glutathione that is present in cells as a defense against undesirable electrophiles. 

Figure 2-9. Reaction scheme for the complete catalytic cycle in glutathione peroxidase (left). Numbers represent calculated reaction barriers using the active-site model. The detailed potential energy diagram for the first elementary reaction, (E-SeH) + H2O2 - (E-SeOH) + H2O, calculated using both the active-site (dashed line) and ONIOM model (grey line) is shown to the right (Adapted from Prabhakar et al. [28, 65], Reprinted with permission. Copyright 2005, 2006 American Chemical Society.)...

From chemical point of view, efficient free radical scavengers must contain substituents with the very weak C—H, O—H, or S—H bonds, from which reactive free radicals are able to abstract a hydrogen atom. It can be seen that the antioxidants discussed above (ascorbic acid, a-tocopherol, ubihydroquinones, glutathione, etc) fall under this category. However, many other compounds manifest free radical scavenging activity in in vitro and in vivo systems. 

Buta-1,3-diene (10.101, Fig. 10.24) is a gaseous chemical used heavily in the rubber and plastics industry, the presence of which in the atmosphere is also a concern. Butadiene is suspected of increasing the risks of hematopoietic cancers, and it is classified as a probable human carcinogen. Butadiene must undergo metabolic activation to become toxic the metabolites butadiene monoepoxide (10.102, a chiral compound) and diepoxybutane (10.103, which exists in two enantiomeric and one meso-form) react with nucleic acids and glutathione [160 - 163], as does a further metabolite, 3,4-epoxybutane-l,2-diol (10.105). Interestingly, butadiene monoepoxide is at least tenfold more reactive than diepoxybutane toward nucleic acids or H20. Conjugation between the C=C bond and the oxirane may account for this enhanced reactivity. 

OrganosuUur compounds have been shown to modulate the activity of glutathione -transferases (GST), a family of enzymes important in detoxification of carcinogens [24], and cytochromes P450 (CYP), a family of enzymes that activate many chemical carcinogens in experimental animals [25]. The effect of proteases inhibition is a new aspect of the biological activity of these plants and further research should be carried out to identify the specific compounds from Allium or Allium products that are responsible for this biochemical effect. 

Kerklaan PRM, Zoetemelk CEM, Mohn GR. 1985. Mutagenic activity of various chemicals in Salmonella strain TA100 and glutathione-deficient derivatives On the role of glutathione in the detoxification or activation of mutagens inside bacterial cells. Biochem Pharmacol 34 2151-2156. 

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