Gluthathione

It is possible that dietary flavonoids participate in the regulation of cellular function independent of their antioxidant properties. Other non-antioxidant direct effects reported include inhibition of prooxidant enzymes (xanthine oxidase, NAD(P)H oxidase, lipoxygenases), induction of antioxidant enzymes (superoxide dismutase, gluthathione peroxidase, glutathione S-transferase), and inhibition of redox-sensitive transcription factors. 

A still more complicated reaction is the chemiluminescent oxidation of sodium hydrogen sulfide, cysteine, and gluthathione by oxygen in the presence of heavy metal catalysts, especially copper ions 60>. When copper is used in the form of the tetrammin complex Cu(NH3) +, the chemiluminescence is due to excited-singlet oxygen when the catalyst is copper flavin mononucleotide (Cu—FMN), additional emission occurs from excited flavin mononucleotide. From absorption spectroscopic measurements J. Stauff and F. Nimmerfall60> concluded that the first reaction step consists in the addition of oxygen to the copper complex ... 

Chemical Basis of Toxicity There is only one comprehensive theory for the action of ozone on biologic organisms—the theory of Chow and Tappel that the initial event is the formation of lipid peroxide and that successive events are an attempt to detoxify this product. The theory was developed from experiments with animals that showed that exposure to ozone increases malonaldehyde, gluthathione peroxidase, glutathione reductase, and G-6-PD ... 

Scheme 67 Formation of the liver toxic metabolite A/-acetyl-4-benzochinonimine and its elimination and detoxification with gluthathione or (A/-acetyl)cysteine.

Figure 2.21 Gluthathione S-trans-ferase enzyme-mediated reaction ultimately yielding a sulfonated metabolite (from Field and Thurman, 1996).

It has been shown that many cancer cell lines that are resistant to cis-Pt have elevated levels of gluthathione (Table I) (92-101) on the other hand, depletion of GSH with buthionine sulfoxime reverses resistance only for the A2780 ovarian carcinoma cell line (93). Resistant cancer cell lines, which have no elevated levels of GSH, could also not be sensitized by depletion of GSH (75, 91, 102). These results are rather controversial and therefore the precise role of GSH in mediating cis-Pt resistance is still unclear at present. More research is necessary to explain the rather low increased levels of GSH with respect to the sometimes significant increase in resistance. 

Mueller LA, Goodman CD, Silady RA, Walbot V. 2000. AN9, a petunia gluthathione S-transferase required for anthocyanin sequestration, is a flavonoid-binding protein. Plant Physiol 123 1561-1570. 

The toxicity of methyl isocyanate comes as a surprise if its high sensitivity to hydrolysis is considered. But actually, it may reach its site of action in the human body largely undecomposed. This is due to the reversible addition of another nucleophile to this heterocumulene. The tripeptide gluthathione, which is supposed to protect the body against oxidizing agents, adds to the C=N double bond of the isocyanate by means of its thiol group whereby the thio-carbamate is formed. When the latter decomposes in a reversal to its formation reaction, it releases the intact toxic methyl isocyanate. 

Habes, D., Morakchi, S., Aribi, N., Farine, J.-P, and Soltani, N., Boric acid toxicity to the German cockroach, Batella germanica Alterations in midgut structure, and acetylcholinesterase and gluthathione S-transferase activity, Pestic. Biochem. Physiol., 84,17, 2006. 

Pertussis toxin consists of two components, the enzymatically active A protomer consisting of a single polypeptide, and the penta-meric B oligomer (Tamura et ai, 1982). The B component is involved in binding to the surface of eukaryotic target cells, and presumably in translocation of the toxin across the plasma membrane. Once inside the cell, the enzymatically active A component needs to undergo activation that depends on reduced gluthathione this effect can be... 

Ascorbic acid Cysteine HCI Thioglycerol Thioglycolic acid Thiosorbitol Gluthathione Retards oxidation... 

Vendeland SC, Deagen JT, Whanger PD. 1992. Uptake of selenotrisulfides of gluthathione and cysteine by brush border membranes from rat intestines. J Inorg Biochem 47 131-140. 

Sakato, K., and Tanaka, H., Advanced Control of Gluthathione Fermentation Process, Biotechnol. Bioeng., 40 904 (1992)... 

Kuo C-FI, Flook JB. Depletion of renal gluthathione content and nephrotoxicity of cephaloridine in rabits, rats, and mice. Toxicol AppI Pharmacol 1982 63 292-302. 

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