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PubMed1990

Peripheral blood T lymphocyte sensitization to thyroid microsomal antigen from patients with Graves' disease negative for circulating anti-thyroid microsomal antibodies.

We have studied thyrocyte HLA-DR expression induced by supernatants of peripheral blood mononuclear cells (PBMC) stimulated by thyroid microsomal antigen (TMA), as an index of sensitization of the T lymphocyte in autoimmune thyroid diseases; we have studied PBMC from 11 normal control persons and 19 patients with Graves' disease (GD) in whom serum anti-thyroid microsomal antibodies (AMA) were either not detectable (9 patients) or were positive (10 patients). Thyrocyte HLA-DR induction in response to TMA-treated PBMC supernatants from GD was significantly different from that of normal controls (p less than 0.05, ANOVA). TMA-stimulated GD PBMC supernatants increased thyrocyte HLA-DR index [TMA 1 ng/ml, SI 143 +/- 82 (mean +/- SD), p less than 0.05], but normal PBMC supernatants did not. However there was no significant difference in response in terms of the thyrocyte HLA-DR expression induced by TMA-stimulated PBMC supernatants between AMA seronegative vs seropositive GD. These results suggest the possibility of some dissociation of the activities of T lymphocytes and B lymphocytes in patients with GD in response to thyroid microsomal antigen with or without anti-thyroid microsomal antibodies.

Adult↗

PubMedDate not supplied

Stability of rat lung and liver microsomal cytochrome P-450 enzyme activities to storage: purified microsomal fraction, postmitochondrial fraction, and whole tissue.

The ability to maintain cytochrome P-450 enzyme levels in stored tissue samples is necessary in order to properly utilize this enzyme system in toxicological and environmental health studies. The stability of enzyme activities associated with microsomal cytochrome P-450 was investigated to determine the best way to handle large numbers of samples and postmortem or biopsy lung and liver tissue. Long-term storage in cold buffer resulted in diminished activities in purified microsomes and whole tissue. Benzo[a]pyrene hydroxylase and 7-ethoxycoumarin deethylase, however, were stable when the purified microsomal fraction, postmitochondrial fraction, or whole tissue was stored at -80 degrees C, but care should be exercised in the freezing and thawing procedures.

Animals↗

PubMed1990

Partial characterization of microsomal sialyltransferase from chicken liver and hepatoma Mc-29: II. Measurement of enzyme activities utilizing microsomal glycoproteins as exogenous acceptors.

Microsomal sialyltransferase was assayed in chicken liver and hepatoma Mc-29 utilizing liver and hepatoma microsomal glycoprotein fractions, treated with Triton X-100, as exogenous acceptors. In a homologous assay system containing enzyme and acceptor from one and the same tissue no quantitative dependence of enzyme activity was revealed with increasing amount of the acceptor. In mixed experiments in which liver enzyme activity was tested towards hepatoma acceptor glycoproteins, a gradual drop in sialyltransferase activity occurred with increasing quantities of the acceptor. This effect seems to be a consequence of the presence of some inhibitor in the microsomal fractions from the hepatoma cells.

Animals↗

PubMed1984

Inhibition of calcium sequestration activity of liver microsomes by 4-hydroxyalkenals originating from the peroxidation of liver microsomal lipids.

Aldehydes released during peroxidation of liver microsomal lipids and identified as 4-hydroxyalkenals (4-hydroxynonenal being quantitatively the most significant) strongly inhibited the calcium sequestration activity of liver microsomes. The ID50 for 4-hydroxynonenal was 42 microM. The inhibition appeared to be correlated with the amount of the aldehyde bound to the microsomal protein. In rats intoxicated with BrCCl3 significant amounts of protein-bound aldehydes were formed at only 5 min after poisoning, a time at which the calcium sequestring capacity is markedly inhibited.

Aldehydes↗

PubMed1991

Delta 5-desaturation of dihomogammalinolenic acid (20:3(n-6)) into arachidonic acid (20:4(n-6)) by rat liver microsomes and incorporation of fatty acids in microsome phospholipids.

Liver microsomes of rats fed an essential fatty acid (EFA)-deficient diet or a commercial balanced diet were used to study the effect of incubation time on the delta 5-desaturation of [14C]dihomogammalinolenic acid (20:3(n-6)) into arachidonic acid (20:4(n-6)) and incorporation of the two acids into microsomal phospholipids. The EFA-deficient diet highly increased the desaturation rate of 20:3(n-6). Incorporation of the formed 20:4(n-6) into microsomal phospholipids was also increased but at saturating concentration of substrate only. At early times of incubation, the precursor 20:3(n-6) was rapidly incorporated into phospholipids. Formation and incorporation of 20:4(n-6) into phospholipids proceeded more progressively. Data suggest that desaturation of 20:3(n-6) and incorporation of both 20:3(n-6) and 20:4(n-6) into phospholipids occur concomitantly and independently.

8,11,14-Eicosatrienoic Acid↗

PubMed1987

In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins.

We have studied the metabolism of VP-16-213 (etoposide, VP-16), an antitumor agent, by mouse liver microsomes to reactive intermediates and the subsequent covalent binding to microsomal proteins. This metabolism was shown to involve the O-demethylation of VP-16 and resulted in the formation of a 3',4'-dihydroxy derivative (DHVP-16) which was identified by both HPLC and mass spectrometry. The formation of DHVP-16 was cytochrome P-450-mediated as indicated by its dependence on NADPH, its increased production following treatment of mice with phenobarbital, and its marked inhibition by SKF-525A and piperonyl butoxide. Furthermore, DHVP-16 formation required oxygen. Microsomal incubation of VP-16 resulted in an irreversible binding of the drug to the proteins, which was also shown to be cytochrome P-450 dependent. The covalent binding of the VP-16 metabolite(s) was inhibited by DHVP-16 in a dose-dependent fashion, suggesting that the reactive intermediates that bound to proteins were derived from DHVP-16. Electron spin resonance studies indicated that the same semiquinone radical was formed during enzymatic (oxidation or reduction) metabolism of DHVP-16 and the o-quinone derivative of VP-16 (VP-16-Q). VP-16-Q and its semiquinone radical are suggested to be the bioalkylating species.

Animals↗

PubMed1983

Effects of dimethylnitrosamine on metabolism of N,N-dimethylaniline by rat liver microsomes. A comparative study of treatment in vivo, in isolated liver perfusion and in the microsomal system.

The effect of dimethylnitrosamine (DMN) on rat liver microsomal detoxication was studied, using the non-carcinogenic aromatic amine N,N-dimethylaniline (dimethylaniline) as substrate. Prior to the preparation of microsomes, the rat liver was exposed to DMN either in vivo (by i.p. injection) or in the isolated liver perfusion system (by addition to the perfusion medium). DMN treatment in vivo (20 mg/kg body wt.) caused a 40% increase in dimethylaniline N-oxygenation and a 30% decrease in dimethylaniline C-oxygenation. When DMN was added to the perfusion medium to a final concentration of 5 or 25 mM, a similar effect was observed. With the 5 mM dose, C-oxygenation was decreased by 20% with a non-significant increase in N-oxygenation. The higher dose caused a 50% increase in N-oxygenation, whereas the decrease in C-oxygenation remained at 20%. When microsomes were incubated with both DMN (5 mM) and dimethylaniline (5 mM) in the system, a small but significant decrease in both N- and C-oxygenation of dimethylaniline was observed. The effect of DMN on the amino acid incorporation into liver and plasma proteins was also studied in the liver perfusion system. The synthesis of both liver and plasma proteins was reduced by DMN.

Aniline Compounds↗

PubMed2006

Reduction of Nomega-hydroxy-L-arginine to L-arginine by pig liver microsomes, mitochondria, and human liver microsomes.

Nomega-Hydroxy-L-arginine, the intermediate in nitric oxide formation from L-arginine catalyzed by NO synthase, can be released into the extracellular space. It has been suggested that it can circulate and exert paracrine effects. Since it cannot only be used as substrate by NO synthases, but can also be oxidized by cytochrome P450 and other hemoproteins in a superoxide-dependent manner, it has been proposed that it can serve as NO donor. In the present study, the in vitro reduction of Nomega-hydroxy-L-arginine was examined. Pig and human liver microsomes as well as pig liver mitochondria were capable of reducing Nomega-hydroxy-L-arginine to L-arginine in an oxygen-insensitive enzymatic reaction. These results demonstrate that this metabolic pathway has to be considered when suggesting Nomega-hydroxy-L-arginine as NO-precursor. The reconstituted liver microsomal system of a pig liver CYP2D enzyme, the benzamidoxime reductase, was unable to replace microsomes to produce L-arginine from Nomega-hydroxy-L-arginine.

Animals↗

PubMed1999

O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants.

The biotransformation of venlafaxine (VF) into its two major metabolites, O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) was studied in vitro with human liver microsomes and with microsomes containing individual human cytochromes from cDNA-transfected human lymphoblastoid cells. VF was coincubated with selective cytochrome P450 (CYP) inhibitors and several selective serotonin reuptake inhibitors (SSRIs) to assess their inhibitory effect on VF metabolism. Formation rates for ODV incubated with human microsomes were consistent with Michaelis-Menten kinetics for a single-enzyme mediated reaction with substrate inhibition. Mean parameters determined by non-linear regression were: Vmax = 0.36 nmol/min/mg protein, K(m) = 41 microM, and Ks 22901 microM (Ks represents a constant which reflects the degree of substrate inhibition). Quinidine (QUI) was a potent inhibitor of ODV formation with a Ki of 0.04 microM, and paroxetine (PX) was the most potent SSRI at inhibiting ODV formation with a mean Ki value of 0.17 microM. Studies using expressed cytochromes showed that ODV was formed by CYP2C9, -2C19, and -2D6. CYP2D6 was dominant with the lowest K(m), 23.2 microM, and highest intrinsic clearance (Vmax/K(m) ratio). No unique model was applicable to the formation of NDV for all four livers tested. Parameters determined by applying a single-enzyme model were Vmax = 2.14 nmol/min/mg protein, and K(m) = 2504 microM. Ketoconazole was a potent inhibitor of NDV production, although its inhibitory activity was not as great as observed with pure 3A substrates. NDV formation was also reduced by 42% by a polyclonal rabbit antibody against rat liver CYP3A1. Studies using expressed cytochromes showed that NDV was formed by CYP2C9, -2C19, and -3A4. The highest intrinsic clearance was attributable to CYP2C19 and the lowest to CYP3A4. However the high in vivo abundance of 3A isoforms will magnify the importance of this cytochrome. Fluvoxamine (FX), at a concentration of 20 microM, decreased NDV production by 46% consistent with the capacity of FX to inhibit CYP3A, 2C9, and 2C19. These results are consistent with previous studies that show CYP2D6 and -3A4 play important roles in the formation of ODV and NDV, respectively. In addition we have shown that several other CYPs have important roles in the biotransformation of VF.

Animals↗

PubMed1979

Effect of thiourea on microsomal oxidation of alcohols and associated microsomal functions.

Thiourea and diethylthiourea, two compounds which react with hydroxyl radicals, inhibited NADPH-dependent microsomal oxidation of ethanol and 1-butanol. Inhibition by both compounds was more effective in the presence of the catalase inhibitor, azide. Inhibition by thiourea was noncompetitive with respect to ethanol in the absence of azide but was competitive in the presence of azide. Urea, a compound which does not react with hydroxyl radicals or H2O2, was without effect. Thiourea had no effect on NADH- and NADH-cytochrome c reductase, NADPH oxidase, and NADH- and NADPH-dependent oxygen uptake. Thiourea inhibited the activities of aniline hydroxylase and aminopyrine demethylase. Thiourea, but no other hydroxyl radical scavengers, e.g., dimethyl sulfoxide, mannitol, and benzoate, reacted directly with H202 and decreased H2O2 accumulation in the presence of azide. Therefore the actions of thiourea are complex because it can react with both hydroxyl radicals and H2O2. Differences between the actions of thiourea and those previously reported for dimethyl sulfoxide, mannitol, and benzoate, e.g., effects on drug metabolism, effectiveness of inhibition in the absence of azide, or kinetics of the inhibition, probably reflect the fact that thiourea reacts directly with H2O2 whereas the other agents do not. The current results remain consistent with the concept that microsomal oxidation of alcohols involves interactions of the alcohols with hydroxyl radicals generated from microsomal electron transfer.

Aminopyrine N-Demethylase↗

PubMed2002

Some coumarins and triphenylethene derivatives as inhibitors of human testes microsomal 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 3): further studies with tamoxifen on the rat testes microsomal enzyme.

The 7-hydroxycoumarins, umbelliferone and 4-methylumbelliferone (IC50 = 1.4 and 1.9 microM, respectively) were potent inhibitors of human testes microsomal 17beta-HSD (type 3) enzyme whereas 7-methoxycoumarin, 4-hydroxycoumarin and 7-ethoxycoumarin had little or no inhibitory activity. Analogues of the weak inhibitory triphenylethenes tamoxifen and clomiphene but lacking the basic substituent, were weak inhibitors of the human microsomal enzyme. Inhibitory activity was improved by replacement of the triphenylethene structure with a triphenylmethyl (17, 52.6% inhibition) or phenylpropyl (16, 94.8%, IC50 = 42.1 microM) skeleton. Further studies on tamoxifen using rat testes microsomal 17beta-HSD showed that the inhibition was time-dependent and irreversible but not specifically mechanism-based.

17-Hydroxysteroid Dehydrogenases↗

PubMed1980

Coalescence of microsomal vesicles from rat liver: a phenomenon occurring in parallel with enhancement of the glycosylation activity during incubation of stripped rough microsomes with GTP.

Rough microsomes from rat liver have been subjected to various treatments and incubated afterwards with UDP-N-acetyl-[14C]glucosamine and GDP-mannose in the presence of GTP (0.5 mM), or of other nucleotides. In agreement with earlier results from this laboratory, the preparations previously treated to strip off the ribosomes and incubated in the presence of GTP assembled dolichol-linked oligosaccharides and transferred these oligosaccharides to endogenous protein acceptors much more actively than untreated preparations, or stripped preparations incubated in the absence of GTP. Thin-section and freeze-fracture electron microscopy have revealed that pyrophosphate-treated preparations incubated with GTP are aggregated and contain numerous vesicles as large as 1-4 micrometer, or more. Such large vesicles were not present before incubation and thus were considered to have been formed through coalescence of regular-sized ones. Like glycosylation, the coalescence phenomenon depends upon the removal of ribosomes, because it occurred whether ribosomes had been stripped, at least partly, with pyrophosphate, KCl, or puromycin, but not when rough microsomes had been washed with 0.25 M sucrose or with KCl and MgCl2. Like glycosylation, it also depends on the addition of GTP and was not induced by ATP, UTP, CTP, and nonhydrolysable analogues of GTP. Rough microsomes coalesced, however, when pyrophosphate-treated preparations were incubated with GTP in the absence of nucleotide sugars, or in the presence f tunicamycin, indicating that the coalescence phenomenon does not result from the glycosylation of some membrane constituents.

Acetylglucosamine↗

PubMed1977

The in vivo toxicity of CS2 to liver microsomes: binding of labelled CS2 and changes of the microsomal enzyme activities.

The binding of 35S and 14C labelled CS2 to liver microsomes was studied in control and phenobarbitone pretreated rats 3 and 6 hrs after an intraperitoneal injection. The level of hepatic cytochrome P-450, the activities of epoxide hydratase and UDP-glucuronosyltransferase were analyzed in the same animals. The binding of the sulphur label was considerably higher than that of carbon 3 hrs after the injection, the difference being less evident at 6 hrs.T he measurable P-450 declined after the CS2 injection. It was approximately 40% in the phenobarbitone pretreated rats and 60% in control rats of the values of animals which were not treated with CS2. CS2 did not affect microsomal epoxide hydratase activity, while it increased the measurable activity of UDP-glucuronosyltransferase. The increase was evident 3 hrs after the injection of CS2 in the phenobarbitone pretreated rats. It could also be detected in the control animals 6 hrs after the injection. The present data suggest that the change in the measureble P-450 results from the binding of the metabolite(s) of CS2 to the cytochrome, and its subsequent degradation. The increase in measurable UDP-glycuronosyltransferase activity results probably from the activated perturbation of the structure of microsomal membrane by the metabolites of CS2 in vivo.

Animals↗

PubMed1976

Effects of insecticide synergists on microsomal oxidation of estradiol and ethynylestradiol and on microsomal drug metabolism.

1. Oxidation of estradiol and ethynylestradiol at ring A and ring B by rat liver microsomes and NADPH-regenerating system in vitro is inhibited by the two arylimidazole insecticide synergists, 3-bromophenyl-4(5)-imidazole and 1-naphthyl-4(5)-imidazole, but not by the benzothiadiazole insectide synergists 6-nitro-1,2,3-benzothiadiazole and 5,6-dimethyl-1,2,3-benzothiadiazole. The Ki of the most potent inhibitor, 1-naphthyl-4(5)-imidazole, was 3 X 10(-6) M. 2. 6-Nitro-1,2,3-benzothiadiazole (10(-6) M), which did not inhibit hydroxylation of the estrogens, inhibited oxidation of aniline and demethylation of ethylmorphine, p-nitroanisole, and aminopyrine by 30-70%. 5,6-Dimethyl-1,2,3-benzothiadiazole inhibited only demethylation of p-nitroanisole and aminopyrine. From these results the presence of different hepatic microsomal mixed function oxidases may be inferred. 3. 1-Naphthyl-4(5)-imidazole, the most potent inhibitor of hydroxylation of drugs and estrogen rings A and B, also inhibited microsomal estrogen-16alpha-hydroxylation. 4. These data show that insecticide synergists may effect the breakdown of estrogenic hormones in the organism.

Animals↗

PubMed1993

Fluidity of the microsomal membrane and cytochrome P450 reduction kinetics of pig liver microsomes as a consequence of organic solvent impact.

1. The effect of the aromatic solvents toluene, xylene and ethylbenzene on microsomal membrane fluidity and anaerobic NADPH-reduction kinetics were studied. 2. The relation of membrane fluidity to the kinetics of cytochrome P450 reduction by NADPH-cytochrome P450 reductase was examined with regard to a membrane-mediated molecular organization of the multienzyme components of the monooxygenase system. 3. Membrane fluidity changes were detected with the steady-state pyrene excimer formation method and with fluorescence lifetime measurements after incubation of the microsomes with organic solvents. 4. Increase in membrane fluidity in presence of organic solvents leads to a small but significant decrease of the rate constant of the cytochrome P450 reduction kinetics and a change in the relative amplitudes of the components of the biphasic response. 5. The results support the idea of a molecular organization of cytochrome P450 in clusters. Fluidization of the microsomal membrane by organic solvents increase the cytochrome P450 cluster formation.

Animals↗

PubMed1990

The in vitro NADPH-dependent inhibition by CCl4 of the ATP-dependent calcium uptake of hepatic microsomes from male rats. Studies on the mechanism of the inactivation of the hepatic microsomal calcium pump by the CCl3.radical.

The hepatotoxicity of CCl4 is mediated through its initial reduction by cytochrome P-450 to the CCl3.radical. This radical then damages important metabolic systems such as the ATP-dependent microsomal Ca2+ pump. Previous studies from our laboratory on isolated microsomes have shown that NADPH in the absence of toxic agents inhibits this pump. We have now found in in vitro incubations that CCl4 (0.5-2.5 mM) enhanced the NADPH-dependent inhibition of Ca2+ uptake from 28% without CCl4 to a maximum of 68%. These concentrations are in the range found in the livers and blood of lethally intoxicated animals (Dambrauskas, T., and Cornish, H. H. (1970) Toxicol. Appl. Pharmacol. 17, 83-97; Long, R.M., and Moore, L. (1988) Toxicol. Appl. Pharmacol. 92, 295-306) and are toxic to cultured hepatocytes (Long, R. M., and Moore, L. (1988) Toxicol. Appl. Pharmacol. 92, 295-306). The inhibition of Ca2+ uptake was due both to a decrease in the Ca2(+)-dependent ATPase and to an enhanced release of Ca2+ from the microsomes. The NADPH-dependent CCl4 inhibition was greater under N2 and was totally prevented by CO. GSH (1-10 mM) added during the incubation with CCl4 prevented the inhibition. This protection was also seen when the incubations were performed under nitrogen. When samples were preincubated with CCl4, the CCl4 metabolism was stopped, and then the Ca2+ uptake was determined; GSH reversed the CCl4 inhibition of Ca2+ uptake. This reversal showed saturation kinetics for GSH with two Km values of 0.315 and 93 microM when both the preincubation and the Ca2+ uptake were performed under air, and 0.512 and 31 microM when both were performed under nitrogen. Cysteine did not prevent the NADPH-dependent CCl4 inhibition of Ca2+ uptake. CCl4 increased lipid peroxidation in air, but no lipid peroxidation was seen under nitrogen. Lipid peroxidation was only modestly reversed by GSH. GSH did not remove 14C bound to samples preincubated with the 14CCl4. Although EDTA (100 microM) decreased the CCl4 inhibition, the metal-complexing agents deferoxamine (100 microM) and diethyldithiocarbamate (100 microM) had no effect on the inhibition of the pump. Similarly, the reactive oxygen scavengers catalase (65 micrograms/ml), superoxide dismutase (15 micrograms/ml), mannitol (10 mM), and dimethyl sulfoxide (50 mM) also had no effect. Our results suggest that the initial toxicity of CCl4 for the Ca2+ pump results from the metabolism of CCl4 to the CCl3. radical. This radical then directly oxidizes the Ca2+ pump, leading to decreased Ca2+ uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Immunochemical study on the contributions of two molecular species of microsomal cytochrome P-450 to the metabolism of benzo(a)pyrene by rat liver microsomes.

The roles of two species of cytochrome P-450, the major cytochrome P-450 components of liver microsomes of phenobarbital-treated rats (PB-P-450) and 3-methylcholanthrene-treated rats (MC-P-448), were studied in the metabolism of benzo(a)pyrene in rat liver microsomes in vitro. Benzo(a)pyrene was incubated with polychlorinated biphenyl-treated rat liver microsomes, in which PB-P-450 and MC-P-448 constituted about 45 and 24% of the total cytochrome P-450, respectively. Then the metabolites were separated into those soluble in ethyl acetate and in water, and those covalently bound to protein. Using high-pressure liquid chromatography, the ethyl acetate-soluble metabolites were separated into three major groups, phenols, quinones, and dihydrodiols, including peaks of three unknown materials. Addition of anti-MC-P-448 immunoglobulin to the reaction mixture completely inhibited the formation of all ethyl acetate-soluble metabolites. In contrast, anti-PB-P-450 immunoglobulin did not inhibit the formations of 4,5-dihydro-4,5-dihydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene; partially inhibited the formations of 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, 9, 10-dihydro-9, 10-dihydroxybenzo(a)pyrene, and the three unknown materials; and caused 30 to 40% enhancement of the formations of 9-hydroxy-benzo(a)pyrene and benzo(a)pyrene-3,6-dione and 80% enhancement of that of benzo(a)pyrene-1,6-dione. Antibody against MC-P-448, but not against PB-P-450, also caused 75% inhibition of the formation of water-soluble metabolites and 85% inhibition of formation of benzo(a)pyrene metabolites covalently bound to protein. These results show that MC-P-448 is important in the metabolism of benzo(a)pyrene.

Animals↗

PubMed1982

[Interaction of the Cu(Lys)2 complex with the NADPH-dependent microsomal electron transport system and microsomal membrane].

The low molecular weight analog of superoxide dismutase, th Cu(Lys)2 complex inhibits the oxidation of type I (piperidinoanthraquinone) and type II(aniline) substrates catalyzed by cytochrome P-450. This fact is not associated with the conversion of cytochrome P-450 into the inactive form--cytochrome P-420. It was shown that the method of determining the activity of NADPH-cytochrome c-reductase by the cytochrome c reduction rate cannot be employed in the presence of the Cu(Lys)2 and Cu(Tyr)2 complexes. Potassium ferricyanide was used to demonstrate that Cu(Lys)2 does not affect the NADPH-cytochrome c-reductase activity. The inhibiting effect of Cu(Lys)2 on the microsomal oxidation of the substrates does not result from the interaction of the complex with the components of the NADPH-dependent microsomal electron transport system. The effect observed can be accounted for by the dismutase-like action of the complex on the superoxide radicals generated during the microsomal oxidation of the substrates. The interaction of Cu(Lys)2 with the membrane was studied by the ESR method using stable nitroxide rabicais. It was shown that the complex cannot freely diffuse through the lipid bilayer membrane. A model for Cu(Lys)2 incorporation into the membrane is proposed.

Animals↗