Of glutathione

The carbon sulfur bond in LTC4 is formed by the reaction of glutathione (Section 15 13) with leukotriene A4 (LTA4) LTA4 is an epoxide Sug gest a reasonable structure for LTA4... 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

NKOH, EtOH, 20°, 5-10 min 80% yield. 5-2,2-Bis(carboethoxy)ethyl thioether, stable to acidic reagents such as trifluoroacetic acid and hydrogen bromide/acetic acid, has been used in a synthesis of glutathione. ... 

FIGURE S.47 The role of glutathione and metabolic pathways involved In the protection of tissues against Intoxication by electrophiles, oxidants and active oxygen species. (Used with permission.)... 

Design and synthesis of glutathione analogs containing heterocyclic fragments 98F721. 

Other bioanalytical applications of systems in which the eluate of a first LC column is sampled in continuous and repetitive intervals and subjected to a second LC dimension are, for example, described by Wheatly et a/. (11) and Matsuoka et al. (12). Wheatly coupled gradient affinity LC with RPLC for the determination of the isoenzymatic- and subunit composition of glutathione 5-transferses in cytosol... 

J. B. Wheatley, J. A. Montali and D. E. Schmidt-Jr, Coupled affinity-reversed-phase high-performance liquid cliromatography systems for the measurement of glutathione 5-transferases in human tissues , 7. Chromatogr. A 676 65 - 79 (1994). 

An exopeptidase that can only degrade a dipeptide. Examples are carnosine dipeptidase I (MEROPS M20.006), which degrades carnosine (beta-Ala-His), and membrane dipeptidase (MEROPS Ml9.001), which is important in the catabolism of glutathione, degrading the dipeptides Cys-Gly. Dipeptidases are included in Enzyme Nomenclature sub-subclass 3.4.13. 

Okada et al. examined the effects of TBT on cellular content of glutathione (GSH) in rat thymocites using a flow cytometer and 5-chloromethylfluorescein diacetate, a fluorescent probe for monitoring the change in the cellular content of GSH. TBT at nanomolar concentrations reduced the cellular content of GSH. There is an important implication on the TBT-induced depletion of cellular GSH since GSH has an important role in protecting the cells against oxidative stress and chemical and metal intoxications. TBT-induced decrease in cellular content of GSH in thymocytes may increase the vulnerability of the immune system. ° ... 

Activities of glutamate-pyruvate transaminase (SGPT, GPT) (EC 2.6.1.2), L-y -glutamyl-transferase (y-GT) (EC 2.3.2.2) and level of triglycerides (TG) in serum, as well as levels of glutathione (GSH) and malondialdehyde (MDA) in the liver were determined. 

Polidoro G, Dillio C, Arduini A, et al. 1982. Glutathione peroxidase and glutathione S-transferase activities in human fetal tissues. Inability of acidic forms of glutathione S-transferase to catalyze the reduction of organic hydroperoxides. Biochem Int 4 637-645. 

Sultatos LG, Woods L. 1988. The role of glutathione in the detoxification of the insecticides methyl parathion and azinphos-methyl in the mouse. Toxicol Appl Pharmacol 96 168-174. 

Sultatos LG, Huang GJ, Jackson O, et al. 1991. The effect of glutathione monoethyl ester on the potentiation of the acute toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate in the mouse. Toxicol Lett 55 77-83. 

Apart from their catalytic function, at least one form of glutathione-5-trans-ferases has the function of simply binding xenobiotics and transporting them, without metabolism. In effect, this is an example of storage (see Section 2.3.3). The form in question is termed ligandin, and binding is associated with one particular subunit. Binding is not associated with catalytic activity. 

Residues of PCBs in animal tissues include not only the original congeners themselves, but also hydroxy metabolites that bind to cellular proteins, for example, transthyretin (TTR Klasson-Wehler et al. 1992 Brouwer et al. 1990 Fans et al. 1993). Small residues are also found of methyl-sulfonyl metabolites of certain PCBs (Bakke et al. 1982, 1983). These appear to originate from the formation of glutathione conjugates of primary epoxide metabolites, thus providing further evidence of the existence of epoxide intermediates. Further biotransformation, including methylation, yields methyl-sulfonyl products that are relatively nonpolar and persistent. 

Ligandin A form of glutathione-5-transferase with a marked capacity for binding certain lipophilic xenobiotics. 

In mammals, peptide hormones typically contain only the a-amino acids of proteins finked by standard peptide bonds. Other peptides may, however, contain nonprotein amino acids, derivatives of the protein amino acids, or amino acids finked by an atypical peptide bond. For example, the amino terminal glutamate of glutathione, which participates in protein folding and in the metabolism of xenobiotics (Chapter 53), is finked to cysteine by a non-a peptide bond (Figure 3—3). The amino terminal glutamate of thyrotropin-... 

Figure 7-12. Use of glutathione S-transferase (GST) fusion proteins to purify recombinant proteins. (GSH, glutathione.)...

Once bilirubin enters the hepatocytes, it can bind to certain cytosolic proteins, which help to keep it solubilized prior to conjugation. Ligandin (a family of glutathione S-transferases) and protein Y are the involved proteins. They may also help to prevent efflux of bilirubin back into the blood stream. 

Figure 32-15. Diagrammatic representation of the three major processes (uptake, conjugation, and secretion) involved in the transfer of bilirubin from blood to bile. Certain proteins of hepatocytes, such as ligandin (a family of glutathione S-transferase) and Y protein, bind intracellular bilirubin and may prevent its efflux into the blood stream. The process affected in a number of conditions causing jaundice is also shown.

Rao et. al recently published another method for the quantitation of the MB fraction. The method is based on the selective activating capacity of dithiothreitol on CR isoenzyme MB, after isoenzyme MM is activated by glutathione (51). Apparently the MB isoenzyme is not activated by glutathione" Eut is activated by dithiothreitol. The difference between CR activities obtained in the presence of glutathione alone and those obtained with both glutathione and dithiothreitol represent MB activity. The correlation is excellent (r 0.998) between the activity of MB in the isoenzyme mixture determined by this method, and the activity of isolated MB. 

Dekant W, Martens G, Vamvakas S, et al. 1987. Bioactivation of tetrachloroethylene. Role of glutathione S-transferase-catalyzed conjugation versus cytochrome P-450-dependent phospholipid alkylation. Drug Metab Dispos Biol Fate Chem 15 702-709. 

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