Fate Of Glutathione Research Articles

Intranuclear distribution, function and fate of glutathione and glutathione-S-conjugate in living rat hepatocytes studied by fluorescence microscopy.

The availability of fluorescent probes to detect soluble and protein-bound thiols has made it possible to investigate some aspects of reduced glutathione (GSH) metabolism and function in intact rat hepatocytes and in hepatocyte nuclei. Monochlorobimane (BmCl) has been employed to study the subcellular compartmentation of GSH and the formation and fate of the BmCl-GSH conjugate. The occurrence of relatively high concentrations of GSH within the nuclear matrix has been inferred from fluorescence quantitation using image analysis. Concomitant biochemical studies have revealed the presence of a GSH-stimulated ATP hydrolysis and of an ATP-stimulated GSH accumulation in isolated nuclei, providing the molecular basis for nuclear glutathione compartmentation. The contemporary use of fluorescent probes to label nuclear free sulfhydryl groups, proteins and chromatin status led to the demonstration that intranuclear accumulation of glutathione may modulate the thiol/disulfide redox status of nuclear proteins and control chromatin compacting and decondensation.

Significance of the intramolecular transformation of glutathione thiyl radicals to α-aminoalkyl radicals. Thermochemical and biological implications

R. Zhao, J. Lind, G. Merényi and T. E. Eriksen, J. Chem. Soc., Perkin Trans. 2, 1997, 569 DOI: 10.1039/A605727F

The oxidation of p-phenetidine by horseradish peroxidase and prostaglandin synthase and the fate of glutathione during such oxidations

The oxidation of p-phenetidine by horseradish peroxidase and prostaglandin synthase was investigated. The existence of a free radical intermediate formed during enzymatic oxidation was supported by a ratio of hydrogen peroxide: p-phenetidine consumed of 1:2 in the horseradish peroxidase system. Furthermore in both enzyme systems a rapid oxidation of added glutathione was observed and in the presence of the thiol there was a decreased removal of p-phenetidine. This suggests the reduction of a p-phenetidine radical by glutathione generating p-phenetidine and a thiyl radical. The latter react with oxygen and a rapid oxygen uptake was observed during enzymic oxidation in the presence of thiols. That p-phenetidine radicals were produced during horseradish peroxidase catalyzed oxidation of p-phenetidine was supported by experiments using the spin probe OXANOH. This was oxidized to its stable free radical form (OXANO') in an enzyme- and substrate-dependent reaction and the EPR signal obtained was not decreased by SOD (80 μg/ml) or benzoate (10–100 mM). TLC characteristics of the products of the oxidation of p-phenetidine by both enzymes were almost identical inferring a similar mechanism of oxidation. Two of the metabolites were characterized by mass spectrometry and by comparison with reference compounds prepared by chemical oxidation. One metabolite was identified as 4,4'-diethoxyazobenzene, which further supports a radical mechanism, and the other was a p-phenetidine trimer which could exist in both oxidized and reduced forms. On the basis of these observations a mechanism for the oxidation of p-phenetidine and the fate of glutathione during such oxidations is proposed.