Peroxidase reductase

Dehydrogenases Oxiclases, peroxidases Reductases Monooxygenases Dioxygenases... 

Reduction of trypanothione levels in the cells may be achieved in two ways (a) by inhibition of trypanothione peroxidase/reductase activity, or (b) by interference with the polyamine biosynthesis. Interference with the polyamine synthesis will not only lead to a decreased turnover of various polyamines, but will also bring down trypanothione levels in cells, thereby, exposing the parasites to the toxic effects of peroxides and free radicals generated by the host. 

Oxidoreduciases. Enzymes catalysing redox reactions. The substrate which is oxidized is regarded as the hydrogen donor. This group includes the trivially named enzymes, dehydrogenases, oxidases, reductases, peroxidases, hydrogenases and hydroxylases. 

Thiols are also important protection against lipid peroxidation. Glutathione (7-Glu-Cys-Gly) is used by several glutathione-dependent enzymes such as free-radical reductase (converts vitamin E radical to vitamin E), glutathione peroxidase (reduces hydrogen peroxide and lipid hydroperoxides to water and to the lipid alcohol, respectively), and others. In addition, the thiol group of many proteins is essential for function. Oxidation of the thiol of calcium ATPases impairs function and leads to increased intracellular calcium. Thiol derivatives such as the ovothiols (l-methyl-4-mercaptohistidines) (Shapiro, 1991) have been explored as therapeutics. 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

The present chapter reviews applications in biocatalysis of the ONIOM method. The focus is on studies performed in our research group, in most cases using the two-layer ONIOM(QM MM) approach as implemented in Gaussian [23], The studied systems include methane monooxygenase (MMO), ribonucleotide reductase (RNR) [24, 25], isopenicillin N synthase (IPNS) [26], mammalian Glutathione peroxidase (GPx) [27,28], Bi2-dependent methylmalonyl-CoA mutase [29] and PLP-dependent P-lyase [30], These systems will be described in more detail in the following sections. ONIOM applications to enzymatic systems performed by other research groups will be only briefly described. 

The importance of having adequate supplies of NADPH for the regeneration of these various enzymes cannot be over emphasized. In normal situations this cofactor can be adequately provided by the reductive pentose phosphate pathway. Monitoring the activity of the pentose phosphate pathway has been proposed as a unique way to study the metabolic response to oxidative stress, since the glutathione peroxidase activity is coupled via glutathione reductase to the enzyme glucose-6-phosphate dehydrogenase (Ben Yoseph et ah, 1994). 

Observations Table 1 shows the activity of the antioxidant enzymes of tomato roots after 72 h of exposure of allelochemical stress caused by S. deppei. Catalase (CAT) activity increases by 1.5 fold Ascorbate Peroxidase (APX) decreases 2.3 fold Glutathione reductase (GR) activity does not change with the treatment and Superoxide dismutase (SOD) decreases 1.3 fold. 

O Donnell et al. [70] found that LOX and not cyclooxygenase, cytochrome P-450, NO synthase, NADPH oxidase, xanthine oxidase, ribonucleotide reductase, or mitochondrial respiratory chain is responsible for TNF-a-mediated apoptosis of murine fibrosarcoma cells. 15-LOX activity was found to increase sharply in heart, lung, and vascular tissues of rabbits by hypercholesterolemia [71], Schnurr et al. [72] demonstrated that there is an inverse regulation of 12/15-LOXs and phospholipid hydroperoxide glutathione peroxidases in cells, which balanced the intracellular concentration of oxidized lipids. 

Glutathione redox cycle consists of NADPH, reduced glutathione GSH, glutathione reductase (GR), and glutathione peroxidase (GP) (Reactions (7) and (8)) ... 

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