Glutathione reaction type

The reaction catalyzed by the first of these is illustrated in Table 15-2 (reaction type F). The other two enzymes usually promote the reverse type of reaction, the reduction of a disulfide to two SH groups by NADPH (Eq. 15-22). Glutathione reductase splits its substrate into two halves while reduction of the small 12-kDa protein thioredoxin (Box 15-C) simply opens a loop in its peptide chain. The reduction of lipoic acid opens the small disulfide-containing 5-membered ring in that molecule. Each of these flavoproteins also contains within its structure a reducible disulfide group that participates in catalysis. 

Multiple forms of GST have been demonstrated in the liver of many mammalian species multiple forms also occur in insects. Most GSTs are soluble dimeric proteins with molecular weights ranging between 45,000 and 50,000 daltons. All forms appear to be nonspecific with respect to the reaction types described, although the kinetic constants for particular substrates vary from one form to another. They are usually named from their chromatographic behavior. At least two are membrane-bound glutathione transferases, one of which is involved in metabolism of xenobiotics and is designated... 

The glutathione 5-transferases (GSTs) are a group of enzymes that catalyses a range of reactions that are important in physiological detoxification mechanisms. Three main reaction types have been identified. 

At present, antioxidants are extensively studied as supplements for the treatment diabetic patients. Several clinical trials have been carried out with vitamin E. In 1991, Ceriello et al. [136] showed that supplementation of vitamin E to insulin-requiring diabetic patients reduced protein glycosylation without changing plasma glucose, probably due to the inhibition of the Maillard reaction. Then, Paolisso et al. [137] found that vitamin E decreased glucose level and improved insulin action in noninsulin-dependent diabetic patients. Recently, Jain et al. [138] showed that vitamin E supplementation increased glutathione level and diminished lipid peroxidation and HbAi level in erythrocytes of type 1 diabetic children. Similarly, Skyrme-Jones et al. [139] demonstrated that vitamin E supplementation improved endothelial vasodilator function in type 1 diabetic children supposedly due to the suppression of LDL oxidation. Devaraj et al. [140] used the urinary F2-isoprostane test for the estimate of LDL oxidation in type 2 diabetics. They also found that LDL oxidation decreased after vitamin E supplementation to patients. 

Not only is the leaving group important, but if the reaction has SnI character, the stability of the positive charge left behind is also important. In the examples above, a primary carbocation is difficult to form and therefore the reaction of busulfan with glutathione would likely be a SN2-type reaction, whereas the nitrenium ion and carbocation formed from N -acetylaminofluorene and safrole, respectively, are relatively stable and likely to be Sn 1 -type reactions. 

Another type of activated double bond is found in isocyanates and isothiocyanates. Methylisocyanate was responsible for a disaster in Bhopal, India, in 1984 when approximately 40 tons of the gas were accidentally released leading to the death of thousands of people and injury to many more. Some have called this the worst industrial accident in history. Methylisocyanate reacts with nucleophiles as shown in Figure 8.18—in this case with a thiol. This reaction is reversible, and therefore a glutathione conjugate can act to... 

Glutathione (GSH) is widely distributed in cell tissue. Its biological function is not completely understood but it is thought to be a coenzyme for a Cannizzaro-type reaction interconverting... 

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