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Role of Astrocytes in Maintaining Cerebral Glutathione Homeostasis and in Protecting the Brain Against Xenobiotics and Oxidative Stress
Published in Christopher A. Shaw, Glutathione in the Nervous System, 2018
In addition to its roles in protecting tissues against noxious compounds, GSH has other biological functions. The sulfhydryl of GSH is less reactive than that of free cysteine, and consequently GSH serves as a nontoxic storage form of cysteine. Cysteine can form relatively stable hemithioketals with ketones (e.g., α-keto acids). With aldehydes [e.g., glyoxylate and pyridoxal 5′-phosphate (PLP)], hemithioacetal formation is followed by cyclization to a thiazolidone derivative. High concentrations of cysteine inhibit some key PLP-containing enzymes, including glutamate decarboxylase, and this may contribute to the known neurotoxocity of cysteine. In contrast to cysteine, GSH does not form stable adducts with α-keto acids or with PLP, although it does form a stable adduct with glyoxylate. The concentration of GSH in mammalian tissues ranges from about 0.4 to 12 mM. The concentration of cyst(e)ine in tissues is generally <100 μM. Apparently, the high tissue concentration of GSH results in part from the unusual γ-glutamyl peptide linkage, which confers resistance to peptidases.
3,4-Dihydroxybenzaldehyde attenuates pentachlorophenol-induced cytotoxicity, DNA damage and collapse of mitochondrial membrane potential in isolated human blood cells
Published in Drug and Chemical Toxicology, 2022
Nikhil Maheshwari, Riaz Mahmood
Methylglyoxal is an aldehyde ubiquitously produced from glucose and amino acid metabolism. It readily reacts with amino acids and nucleic acids, thereby impairing their function. RBC glyoxalase system converts methylglyoxal to hemithioacetal in presence of GSH. PCP treatment of RBC induced carbonyl stress by increasing methylglyoxal production. The cells will now require more glyoxalase activity which was, therefore, 2.5 times higher than the control value (Table 5). DHB lowered glyoxylase activity to 1.5 times the control.
The possible role of methylglyoxal metabolism in cancer
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Khalid O. Alfarouk, Saad S. Alqahtani, Saeed Alshahrani, Jakob Morgenstern, Claudiu T. Supuran, Stephan J. Reshkin
MG is isomerised to hemithioacetal adducts and then form (R)-S-lactoylglutathione spontaneously in the presence of glutathione. The reaction is catalysed by a lactoylglutathione lyase (glyoxalase I)25–28.