Peroxidase liver

GSH peroxidase Liver Surf scoter, ruddy duck No Decreased Hoffman et al. (1998)... 

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

The molecular masses of heme catalases are usually significantly higher as compared with peroxidases. If expressed in Lg-1s-1, rate constants for the Fem-TAML activators when compared with catalase from beef liver, which has a molecular weight 250,000 gmol-1 (Table IV, entry 13) (89), look very impressive, viz. 17 L g 1 s-1 for 11 vs. 22 L g 1 s 1 for the enzyme. Nevertheless, the catalase-like activity of the Fem-TAML activators can be suppressed by the addition of electron donors -it is negligible in the presence of the substrates tested in this work. In Nature, catalases display only minor peroxidase-like activity (79) because electron donors bulkier than H202 cannot access the deeply buried active sites of these massive enzymes (90). The comparatively unprotected Fem-TAML active sites are directly exposed to electron donors such that the overall behavior is determined by the inherent relative reactivity of the substrates. 

Catalase and glutathione peroxidase provide two important cellular systems for eliminating H202. Catalase, a 56kDa cytosolic hemoprotein homotetramer that can act without a cofactor, although it may bind NAD(P)H, functions as a peroxidase to convert H202 to water. It can be irreversibly inactivated by oxidation and demonstrates decreased activity after ischemia-reperfusion. Catalase is more abundant in astrocytes than in neurons and in white matter than in gray matter, but it can be induced in neurons by neurotrophins. There is substantially less catalase activity in brain than in other tissues, such as liver. 

Recent work in our laboratories has confirmed the existence of a similar pathway in the oxidation of vindoline in mammals (777). The availability of compounds such as 59 as analytical standards, along with published mass spectral and NMR spectral properties of this compound, served to facilitate identification of metabolites formed in mammalian liver microsome incubations. Two compounds are produced during incubations with mouse liver microsome preparations 17-deacetylvindoline, and the dihydrovindoline ether dimer 59. Both compounds were isolated and completely characterized by spectral comparison to authentic standards. This work emphasizes the prospective value of microbial and enzymatic transformation studies in predicting pathways of metabolism in mammalian systems. This work would also suggest the involvement of cytochrome P-450 enzyme system(s) in the oxidation process. Whether the first steps involve direct introduction of molecular oxygen at position 3 of vindoline or an initial abstraction of electrons, as in Scheme 15, remains unknown. The establishment of a metabolic pathway in mammals, identical to those found in Strep-tomycetes, with copper oxidases and peroxidases again confirms the prospective value of the microbial models of mammalian metabolism concept. 

Indicine IV-oxide (169) (Scheme 36) is a clinically important pyrrolizidine alkaloid being used in the treatment of neoplasms. The compound is an attractive drug candidate because it does not have the acute toxicity observed in other pyrrolizidine alkaloids. Indicine IV-oxide apparently demonstrates increased biological activity and toxicity after reduction to the tertiary amine. Duffel and Gillespie (90) demonstrated that horseradish peroxidase catalyzes the reduction of indicine IV-oxide to indicine in an anaerobic reaction requiring a reduced pyridine nucleotide (either NADH or NADPH) and a flavin coenzyme (FMN or FAD). Rat liver microsomes and the 100,000 x g supernatant fraction also catalyze the reduction of the IV-oxide, and cofactor requirements and inhibition characteristics with these enzyme systems are similar to those exhibited by horseradish peroxidase. Sodium azide inhibited the TV-oxide reduction reaction, while aminotriazole did not. With rat liver microsomes, IV-octylamine decreased... 

Indicine W-oxide Al-Oxide reduction Peroxidase, rat liver microsomes 90... 

A wide spectrum of hepatic lesions has been reported in AIDS (H4), but it is not known whether the changes are related to the presence of HIV-1. Therefore, sections from livers of autopsied patients with AIDS were examined for the presence of HIV-1 antigen p 24 (core) and gp 41 (envelope) by the avidin-biotin-peroxidase complex methods using monoclonal antibodies. The most common histologic abnormalities were steatosis, portal inflammation, Kupffer cell hyperplasia, and focal hepatocellular and bile duct damage. Immunoreactivity for HIV-1 antigens was demonstrated in 80% of cases. 

Several other minor metabolites of phenol have been identified in vitro. The formation of 1,4-dihydroxybenzene and 1,2-dihydroxybenzene in a 20 1 molar ratio was observed in isolated rat liver microsomes incubated with phenol (Sawahata and Neal 1983). Further catalysis to / -benzoquinone, 4,4 -biphenol, and biphenoquinone has been demonstrated in microsomes and in in vitro peroxidase preparations. The benzoquinone products react nonenzymatically with nucleophiles, including cysteine and reduced glutathione, to yield. V-conjugates of 1,4-dihydroxybenzene and 4,4-biphenol (Eastmond et al. 1986 Lunte and Kissinger 1983 Subrahmanyam and O Brien 1985). 

Seleninm in this form is present in three enzymes glutathione peroxidase, iodothyronine deiodinase and thio-redoxin rednctase. Deficiency of selenium therefore decreases the activity of these three enzymes and resnlts, at least in experimental animals, in liver necrosis and mns-cnlar dystrophy. In hnmans, it is known to be a canse of a particnlar form of cardiomyopathy known as Keshan disease which affects children and women. This cardiomyopathy was first described in China in 1979. It is also considered that a deficiency of selenium is a risk factor for cancer. 

When binding of the uncharged BP with DNA is catalyzed by horseradish peroxidase (Cavalieri et al. 1988b) or rat liver microsomes (Cavalieri et al. 1988a), the same pattern of the DNA-depurinating BP derivatives was obtained. As mentioned earlier, horseradish peroxidase activates BP by one-electron oxidation, hence, this result is just as expected (Rogan et al. 1979,1988). 

Lipid peroxidation activity. Solubilized green tea, administered orally to rats for 5 weeks, reduced lipid peroxidation products. The treatment produced increased activity of glutathione (GSFf) peroxidase and GSH reductase, increased content of reduced GSH, a marked decrease in lipid hydroperoxides and malondialdehyde in the liver, an increase in the concentration of vitamin A by about 40%. A minor change in the measured parameters was observed in the blood... 

Coumarin administration in the diet (0.25-0.5%) of male Wistar rats and female ICR/Ha mice for two weeks induced glutathione peroxidase activity in the stomach (1.7-fold) and glutathione A-transferase in the liver (5.3-fold), respectively (Spamins... 

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