scholarly journals Cumene hydroperoxide-dependent oxidation of NNN'N'-tetramethyl-p-phenylenediamine and 7-ethoxycoumarin by cytochrome P-450. Comparison between the haemoproteins from liver and olfactory tissue

1989 ◽  
Vol 261 (3) ◽  
pp. 793-800 ◽  
Author(s):  
C J Reed ◽  
F De Matteis
Keyword(s):  
Olfactory Epithelium ◽  
Peroxidase Activity ◽  
Cumene Hydroperoxide ◽  
Major Product ◽  
Radical Scavenger ◽  
Heterolytic Cleavage ◽  
Nasal Tissue ◽  
Bond Scission ◽  
Olfactory Tissue ◽  
Cytochrome P 450

The interaction of cytochromes P-450 of the liver and olfactory epithelium of male hamsters with cumene hydroperoxide (CHP) has been characterized with regard to the ability of CHP to (1) support 7-ethoxycoumarin-O-de-ethylase (ECOD) activity, (2) support the oxidation of NNN'N'-tetramethyl-p-phenylenediamme (peroxidase activity) and (3) cause inactivation of cytochrome P-450. In the liver, CHP was found to support both ECOD and peroxidase activities while causing only minimal inactivation of cytochrome P-450. In contrast, in the olfactory epithelium CHP was virtually unable to support ECOD activity, peroxidase activity was 4-fold greater than in the liver, and extensive inactivation of cytochrome P-450 occurred. The reasons for these differences have been investigated with particular reference to the mode of cytochrome P-450-catalysed decomposition of CHP, that is, via homolytic or heterolytic cleavage of the hydroperoxide dioxygen bond. In both tissues, cumenol (2-phenylpropan-2-ol) was the major product of CHP decomposition detected. The radical scavenger nitrosobenzene inhibited cumenol formation by 84% in the olfactory epithelium, but by only 38% in the liver. This may indicate that dioxygen-bond scission occurs predominantly homolytically in the nasal tissue, whereas there is a balance between homolysis and heterolysis in the liver. It is suggested that the inability of CHP to support ECOD activity in the olfactory epithelium and the extensive inactivation of cytochrome P-450 that it causes both stem from decomposition of the hydroperoxide occurring homolytically rather than heterolytically in this tissue.

scholarly journals Olfactory cytochrome P-450. Studies with suicide substrates of the haemoprotein

1988 ◽  
Vol 253 (2) ◽  
pp. 569-576 ◽  
Author(s):  
C J Reed ◽  
E A Lock ◽  
F De Matteis
Keyword(s):  
Olfactory Epithelium ◽  
Peroxidase Activity ◽  
Time Course ◽  
Cumene Hydroperoxide ◽  
Enzymic Activity ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome ◽  
Suicide Substrates

1. The olfactory epithelium of male hamsters has been found to be extremely active in the cumene hydroperoxide-supported oxidation of tetramethylphenylenediamine, and this peroxidase activity has been shown to be cytochrome P-450-dependent. 2. The interaction of a series of suicide substrates of cytochrome P-450 with the hepatic and olfactory mono-oxygenase systems has been assessed by determination of peroxidase, 7-ethoxycoumarin O-de-ethylase (ECOD) and 7-ethoxyresorufin O-de-ethylase (EROD) activities after treatment in vivo with these compounds. Chloramphenicol, OOS-trimethylphosphorothiolate and two dihydropyridines [DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) and 4-ethyl DDC (3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine)] all caused similar percentage inhibitions of hepatic and olfactory activities, but the absolute amounts of enzymic activity lost were considerably greater in the latter tissue. In contrast, halothane had little effect upon hepatic cytochrome P-450-dependent reactions, whereas it severely inhibited those of the olfactory epithelium. 3. The time course of loss and recovery of hepatic and olfactory peroxidase, ECOD and EROD activities after a single dose of 4-ethyl DDC was studied. The rates of loss of activity observed were very similar, irrespective of tissue or reaction examined. In the olfactory epithelium, all three activities recovered concurrently and at a rate similar to that of the hepatic peroxidase activity. In contrast, the hepatic de-ethylation of 7-ethoxycoumarin and 7-ethoxy-resorufin recovered significantly more rapidly. 4. It is suggested that this behaviour is due to 4-ethyl DDC acting not only as a suicidal inhibitor but also as an inducer of certain forms of cytochrome P-450 in the liver; in the olfactory epithelium, however, inactivation, but not induction, occurs. Classical inducing agents were reported to have no effect upon olfactory cytochrome P-450, and in the present study neither phenobarbitone nor beta-naphthoflavone treatment had any effect upon olfactory cytochrome P-450-dependent reactions, although it induced those of the liver.

scholarly journals NADPH: cytochrome P-450 reductase in olfactory epithelium Relevance to cytochrome P-450-dependent reactions

1986 ◽  
Vol 240 (2) ◽  
pp. 585-592 ◽  
Author(s):  
C J Reed ◽  
E A Lock ◽  
F De Matteis
Keyword(s):  
Olfactory Epithelium ◽  
Direct Evidence ◽  
Reductase Activity ◽  
Electron Flow ◽  
Male Rats ◽  
Male And Female ◽  
Marked Activity ◽  
Nadh Cytochrome ◽  
Olfactory Tissue ◽  
Cytochrome P 450

The presence of a very active cytochrome P-450-dependent drug-metabolizing system in the olfactory epithelium has been confirmed by using 7-ethoxycoumarin, 7-ethoxyresorufin, hexobarbitone and aniline as substrates, and the reasons for the marked activity of the cytochrome P-450 in this tissue have been investigated. The spectral interaction of hexobarbitone and aniline with hepatic and olfactory microsomes has been examined. By this criterion there was no evidence for marked differences in the spin state of the cytochromes of the two tissues, or for the olfactory epithelium containing a greater amount of cytochrome capable of binding hexobarbitone, a very actively metabolized substrate. Rates of NADPH and NADH: cytochrome c reductase activity were found to be higher in the olfactory epithelium than in the liver, and direct evidence was obtained for a greater amount of the NADPH-dependent flavoprotein in the olfactory microsomes. Investigation of male rats and male and female mice, as well as male hamsters, demonstrated that, in all cases, the cytochrome P-450 levels of the olfactory epithelium were lower than those of the liver, while the 7-ethoxycoumarin de-ethylase and NADPH:cytochrome c reductase activities were higher. A correlation was found between 7-ethoxycoumarin de-ethylase and NADPH:cytochrome c reductase activities for both tissues in all species examined. The ratio of reductase to cytochrome P-450 was found to be considerably higher in the olfactory epithelium (1:2-1:3) than in the liver (1:11-1:15), regardless of the species examined, suggesting that facilitated electron flow may contribute significantly to the cytochrome P-450 catalytic turnover in the olfactory tissue.

A screening method for cytochrome P-450 organic peroxidase activity and application to hydrocarbon-degrading bacterial populations

1987 ◽  
Vol 33 (1) ◽  
pp. 1-5 ◽  
Author(s):  
R. C. Wyndham
Keyword(s):  
Peroxidase Activity ◽  
Oil Sands ◽  
Screening Method ◽  
Cumene Hydroperoxide ◽  
Acinetobacter Calcoaceticus ◽  
Cross Reactivity ◽  
Heavy Oils ◽  
Difference Spectra ◽  
Bacterial Populations ◽  
Cytochrome P 450

A method to detect the expression of hemoproteins with organic hydroperoxide reducing activity was developed to screen bacterial populations isolated from heavy oils and oil sands. The method is based on the activity of cytochrome P-450 as catalyst in the reduction of cumene hydroperoxide by artificial electron donors. There was no cross-reactivity with true peroxidases involved in the reduction of hydrogen peroxide. Cross-reactivity with catalase could be eliminated with appropriate inhibitors but did not normally interfere with the detection method. A preliminary screen resulted in the isolation of Acinetobacter calcoaceticus and a range of Gram-positive bacteria with organic peroxidase activity. Carbon monoxide difference spectra of cell-free extracts of the isolates revealed the presence of a hydrocarbon-inducible cytochrome P-450 in Acinetobacter calcoaceticus and in coryneform and actinomycete bacteria. A CO-binding cytochrome of unknown type with a Soret absorption maximum at 424 nm and cumene hydroperoxidase activity was also detected in some strains.

scholarly journals Abnormal antioxidant defence in some tissues of congenitally obese mice

1984 ◽  
Vol 219 (1) ◽  
pp. 41-49 ◽  
Author(s):  
I D Capel ◽  
H M Dorrell
Keyword(s):  
Glutathione Peroxidase ◽  
Peroxidase Activity ◽  
Cumene Hydroperoxide ◽  
Hepatic Tissue ◽  
Obese Mice ◽  
Glutathione Peroxidase Activity ◽  
Antioxidant Defence ◽  
Reactive Material ◽  
Antioxidant Defence System ◽  
Significant Difference

The concentration of lipoperoxides (estimated as thiobarbituric acid-reactive material) and some components of the antioxidant defence system have been compared in various tissues of lean and congenitally obese mice. NADPH-stimulated lipoperoxide generation in vitro was significantly higher in microsomes (microsomal fractions) prepared from obese hepatic tissue than lean. Plasma, liver and brain lipoperoxide concentration was significantly higher in obese mice. In blood derived from obese mice the concentration of non-enzymic antioxidants including caeruloplasmin and vitamin A was higher, but hepatic retinol concentration was lower in these animals. In all the tissues assayed the glutathione peroxidase activity against H2O2 was less than its activity against cumene hydroperoxide. Assayed with either substrate, glutathione peroxidase activity was significantly higher in the brain and blood of obese mice than their lean counterparts. Conversely, liver glutathione peroxidase was decreased in obese animals, representing 43% of the activity of the lean-mouse liver enzyme against H2O2 and 81% of the cumene hydroperoxide-reducing activity. The liver of obese mice had significantly less, and the kidneys more, oxidized glutathione than the corresponding tissues of lean mice. Further investigations on hepatic tissue indicated that glutathione reductase activity was lower in the obese animals, but there was no significant difference between glucose-6-phosphate dehydrogenase activity in obese and lean mice.

scholarly journals Some effects of vitamin E and selenium deprivation on tissue enzyme levels and indices of tissue peroxidation in rainbow trout (Salmo gairdneri)

1985 ◽  
Vol 53 (1) ◽  
pp. 149-157 ◽  
Author(s):  
J. G. Bell ◽  
C. B. Cowey ◽  
J. W. Adron ◽  
Aileen M. Shanks
Keyword(s):  
Rainbow Trout ◽  
Vitamin E ◽  
Peroxidase Activity ◽  
Cumene Hydroperoxide ◽  
Dietary Vitamin ◽  
Salmo Gairdneri ◽  
Deficient Diet ◽  
Exudative Diathesis ◽  
Malondialdehyde Formation

1. Duplicate groups of rainbow trout (Salrno gairdnert) (mean weight 11 g) were given for 40 weeks one of four partially purified diets that were either adequate or low in selenium or vitamin E or both.2. Weight gains of trout given the dually deficient diet were significantly lower than those of trout given a complete diet or a diet deficient in Se. No mortalities occurred and the only pathology seen was exudative diathesis in the dually deficient trout.3. There was significant interaction between the two nutrients both with respect to packed cell volume and to malondialdehyde formation in the in vitro NADPH-dependent microsomal lipid peroxidation system.4. Tissue levels of vitamin E and Se decreased to very low levels in trout given diets lacking these nutrients. For plasma there was a significant effect of dietary vitamin E on Se concentration.5. Glutathione (GSH) peroxidase (EC 1. 1 1. 1.9) activity in liver and plasma was significantly lower in trout receiving low dietary Se but was independent of vitamin E intake. The ratios of hepatic GSH peroxidase activity measured with cumene hydroperoxide and hydrogen peroxide were the same for all treatments. This confirms the absence of a Se-independent GSH peroxidase activity in trout liver.6. Se deficiency did not lead to any compensatory increase in hepatic GSH transferase (EC 2. 5. 1. 18) activity; values were essentially the same in all treatments.7. Plasma pyruvate kinase (EC 2. 7. 1.40) activity increased significantly in the trout deficient in both nutrients. This was thought to be due to leakage of the enzyme from the muscle and may be indicative of incipient (subclinical) muscle damage.

The carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity is inhibited by the radical scavenger tempol

2013 ◽  
Vol 455 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Raphael F. Queiroz ◽  
Verônica Paviani ◽  
Fernando R. Coelho ◽  
Emerson F. Marques ◽  
Paolo Di Mascio ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Peroxidase Activity ◽  
Radical Scavenger ◽  
Superoxide Dismutase 1 ◽  
Carbonate Radical ◽  
Covalent Dimerization

The nitroxide tempol inhibited the carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity. Tempol acted by scavenging the produced carbonate radical and by recombining with hSOD1-Trp32• radicals as indicated by MS/MS evidence.

Cumene Hydroperoxide-Mediated Formation of Inhibited Complexes of Methylenedioxyphenyl Compounds with Cytochrome P-450

1975 ◽  
Vol 3 (6) ◽  
pp. 967-970 ◽  
Author(s):  
CLIFFORD R. ELCOMBE ◽  
JAMES BRIDGES ◽  
ROBERT H. NIMMO-SMITH ◽  
JURGEN WERRINGLOER
Keyword(s):  
Cumene Hydroperoxide ◽  
Cytochrome P 450 ◽  
Methylenedioxyphenyl Compounds
Sign in / Sign up

Export Citation Format

Share Document