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1.
J. Roy Chowdhury N. Roy Chowdhury Albert D. Moscioni Robert Tukey Thomas Tephly Irwin M. Arias 《Biochimica et Biophysica Acta (BBA)/General Subjects》1983,761(1):58-65
Hepatic uridinediphosphoglucroonate glucuronosyl transferase (UDPglucuronyltransferase, EC 2.4.1.17) functionally heterogeneus; 4-nitrophenol and bilirubin are representative subtrates for two separated from of the enzyme. UDPglucuronyltransferase activity for bilirubin and 4-nitrophenol was separated from solubilized rat liver microsomes by DEAE-cellulose chromatography and corresponding enzymes were purified. A radioimmunoassay was developed using a rabbit antiserum against purified rat 4-nitrophenol-specific UDPglucuronyltransferase, which precipitated enzyme activities toward both 4-nitrophenol and bilirubin. After treatment with triiodothyronine(T3) (0.55 mg/kg body weight), hepatic microsomal UDPglucuronyltransferase activity for 4-nitropheelos was increased 400% as compared to controls; the enzyme activity for bilirubin was decreased by 80%; the changes in the substrate-specific enzyme activities were reflected in the enzymatically active fractions separated after DEAE-cellulose chromatography. The changes in enzyme activities paralleled changes in the concentrations of the two corresponing UDP glucuronyltransferase proteins in the chromatographic fractions, as measured by radioimmunoassay. The results indicate that the opposite effects of T3 on the two forms of UDPglucuronyltransferase activity is due to its differential effect on corresponding enzyme proteins. 相似文献
2.
David Zakim Jovita Goldenberg Donald A. Vessey 《Biochimica et Biophysica Acta (BBA)/General Subjects》1973,297(2):497-502
The rates of synthesis of some glucuronides by liver microsomes from the Gunn strain of rat are abnormally low, but previous investigators of the activity of the p-nitrophenol metabolizing form of UDPglucuronyltransferase (UDPglucuronate glucuronyltransferase, EC 2.4.1.17) have reported normal levels of activity in these animals. Data presented in this paper indicate, however, that this enzyme is abnormal in Gunn rats. Thus, treatment of liver microsomes from normal Wistar rats with phospholipase A (EC 3.1.1.4) or Triton X-100 increases the activity of the p-nitrophenol metabolizing form of UDPglucuronyltransferase 10- and 20-fold, respectively, but these agents do not alter activity in microsomes from homozygous Gunn rats. Similarly, phospholipase A and Triton X-100 activate the o-aminophenol and o-aminobenzoate metabolizing forms of UDPglucuronyltransferase in microsomes from normal rats, but are without effect on the enzyme in microsomes from Gunn rats. In contrast, the rates of synthesis of o-aminophenyl- and o-aminobenzoylglucuronides are increased several fold by addition of diethylnitrosamine to microsomes from Gunn rats indicating that the maximum potential activities of UDPglucuronyltransferases are constrained in liver microsomes from both normal and Gunn rats.These data indicate that assays of UDPglucuronyltransferase in native microsomes are not sufficient for delineating the full extent of the defect in the Gunn rat, that there are defects in the function of at least two proteins in liver microsomes from these animals, and that there are abnormal interrelations between some forms of microsomal UDPglucuronyltransferase and their phospholipid environments. 相似文献
3.
P L Jansen I M Arias 《Comparative biochemistry and physiology. B, Comparative biochemistry》1977,56(3):255-258
1. The main bilirubin conjugate in bile of spiny dogfish (Squalus Acanthias) and small skate (Raja Erinacea) is bilirubin monoglucuronide. 2. Microsomal preparations from dogfish and small skate liver have similar bilirubin UDPglucuronyltransferase (UDPGT) activity and catalyze the conjugation of bilirubin with glucose from UDPglucose. 3. The activity of bilirubin glucosidation (UDPGT) was 0.5 times UDPG1T activity in dogfish and 0.15 times in skate liver microsomes. 4. Sodium cholate increased UDPGT and UDPG1T activities in dogfish and skate liver microsomal preparations only minimally, but the detergent markedly increased thermolability of UDPGT in skate liver microsomes. 相似文献
4.
Jacques Dainat F. de Balbian Verster R. Zand O. Z. Sellinger 《Neurochemical research》1979,4(5):557-565
The activity of tRNA methyltransferases present in the cerebellum of 6- and 21-day-old nonicteric and icteric Gunn rats was compared using purifiedE. coli tRNAs as substrates. At 6 days the tRNA methyltransferases of the icteric animals were significantly more effective in methylating tRNAGlu
2 and tRNAPhe than were those of their nonicteric counterparts. This relationship reversed itself at 21 days. The action of the tRNA methyltransferases from the 6-day-old icteric animals led to higher proportions of 1-methyladenine in tRNAGlu
2 and tRNAPhe than were obtained using the corresponding enzymes of the nonicteric animals. The proportion ofN
2-methylguanine was also higher, yet only in tRNAfMet and not in tRNAPhe. The study reveals much more extensive fluctuations in the activity and in the substrate recognition specificity among the cerebellar tRNA methyltransferases of the icteric than among those of the nonicteric controls during the crucial 6–21 day period of cerebellar development. 相似文献
5.
In rat liver microsomal preparations, bilirubin markedly stimulated the glucuronidation of morphine and p-nitrophenol catalyzed by UDPglucuronyltransferase (UDPGT, EC 2.4.1.17). The activation was not due to contamination of bilirubin with bile acids. At equimolar concentrations, the activating effect of bilirubin was greater than that produced by deoxycholate, a detergent well known as an activator of UDPGT. Other results suggest that bilirubin activation of UDPGT is similar to that produced by detergents. In experiments, the rate of urinary excretion of morphine glucuronide in rats treated with bilirubin was twice that of control animals. These results suggest that bilirubin may be a physiologic activator of UDPGT activity. 相似文献
6.
Expression of four phenobarbital-inducible cytochrome P-450s in liver, kidney, and lung of rats 总被引:1,自引:0,他引:1
Specific antibodies were prepared against cytochromes P450 PB-1, PB-2, PB-4, and PB-5 purified from hepatic microsomes of male rats treated with phenobarbital. With these antibodies, the levels of these four cytochrome P450s in hepatic, renal, and pulmonary microsomes of male rats that were untreated, treated with phenobarbital, or treated with 3-methylcholanthrene were examined. P450 PB-1 and PB-2 were present in moderate amounts in hepatic microsomes of untreated male rats and were induced 2- to 3-fold with phenobarbital. Also, the expression of these forms was suppressed by 3-methylcholanthrene. These forms were not detected in the renal or pulmonary microsomes of untreated rats or rats treated with phenobarbital or 3-methylcholanthrene. P450 PB-4 and PB-5 were found in the hepatic microsomes of untreated male rats at a low level but were induced with phenobarbital more than 50-fold. P450 PB-4 and PB-5 were not detected in renal microsomes; only P450 PB-4 or a closely related form was present in the pulmonary microsomes of untreated male rats, and its level was not changed by phenobarbital treatment. The constitutive presence of P450 PB-4 in pulmonary microsomes was confirmed by the investigation of testosterone metabolism. Purified P450 PB-4 had high testosterone 16 alpha- and 16 beta-hydroxylation activity in a reconstituted system. The testosterone 16 beta-hydroxylation activity of hepatic microsomes was induced with phenobarbital, and more than 90% of the testosterone 16 beta-hydroxylation activity of hepatic microsomes from rats treated with phenobarbital was inhibited by anti-P450 PB-4 antibody.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
Hideyuki Maeda 《Free radical research》2016,50(7):720-731
Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with sleep apnea syndrome (SAS). Intermittent hypoxia (IH) and a high-fat diet (HFD) reproduce SAS and NAFLD, respectively, in rodents. In this study, rats were fed either an HFD or a standard diet (SD) for 2 weeks, and breathed either IH air or normoxic air for 4 days (early phase) or 6 weeks (late phase), with the same diets maintained during the exposure. HFD increased hepatic lipid accumulation, as detected by oil-red staining and triglyceride content. However, IH exposure reversed the hepatic steatosis at the late phase in these HFD-rats. IH exposure also increased hepatic expression of HO-1 and iron-binding protein ferritin-1 at the late phase, in association with increase in serum iron, bilirubin, and hepatic levels of lipid peroxides, such as 4-hydroxy-2-nonenal (HNE). IH exposure increased serum levels of hemoglobin (Hb) at the early phase and immunofluorescence of Hb and HO-1 in CD68-positive Kupffer cells (KCs) at the late phase. These findings support that IH induces erythrocytosis, erythro-phagocytosis, and generation of Hb in the KCs. The Hb promotes HO-1 expression in KCs, thereby produces iron, bilirubin, and carbon monoxide (CO). The iron would be either sequestrated by ferritin-1, transferred to the bone marrow for erythropoiesis, or would produce hydroxyradicals and HNE in the liver of rats fed an HFD. HNE might also contribute to the upregulation of HO-1, transferrin-1, and IκB, thereby limiting hepatic steatosis and inflammation via inhibition of nuclear factor κB (NFκB) activation. 相似文献
8.
Hepatic glucuronidation of the asymmetrical natural bilirubin molecule results in formation of two different positional isomers, bilirubin C-8 monoglucuronide and bilirubin C-12 monoglucuronide. In view of the existence of multiple isoforms of UDPglucuronyltransferase, which is the microsomal enzyme system responsible for bilirubin esterification, we performed kinetic analysis of microsomal glucuronidation of bilirubin and a number of its structural congeners to determine whether synthesis of the two monoglucuronide isomers involved two distinct substrate-binding sites or reflected two different modes of binding to a single catalytic site. Both isomers were found in all tested species (man, rat, guinea pig, sheep), but there were marked species differences in the C-8/C-12 ratio of monoglucuronide found in bile or formed by liver microsomes. Correspondence between in vivo and in vitro results for such regioselectivity of glucuronidation was excellent in each species. On the basis of our results of kinetic analysis of bilirubin esterification at variable pigment substrate concentrations and inhibition studies with alternative substrates, we postulate that both natural monoglucuronide isomers are synthesized at a single binding site. Possible mechanisms responsible for the markedly regioselective esterification of bilirubin by rat and sheep liver were investigated by study of glucuronidation of selected structural analogues of the pigment. Our results do not support explanations of regioselectivity of bilirubin glucuronidation in terms of (i) preferential binding of either the C-8- or C-12-containing dipyrrolic half of the asymmetrical bilirubin molecule or (ii) enantioselective complexation of bilirubin UDPglucuronyltransferase to one of the two chirality enantiomers of intramolecularly hydrogen-bonded bilirubin.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
Rat renal microsomes catalyzed the glucuronidation of l-naphthol, 4-methylumbelliferone and p-nitrophenol, whereas morphine and testosterone conjugation were not detected. In contrast, all five substrates were conjugated by hepatic microsomes; the activity was typically 5-10 times greater than with renal microsomes. Renal microsomal UDP-glucuronyltransferase toward l-naphthol was fully activated (six-fold) by 0.03% deoxycholate while the hepatic enzyme was fully activated (eight-fold) by 0.05% deoxycholate. Full activation of hepatic UDP-glucuronyltransferase occurred when microsomes had been preincubated at 0 C with deoxycholate for 20 min. This effect of preincubation was not observed with renal microsomes. The presence of 0.25M sucrose in the buffers during renal microsomal preparation resulted in a two-fold greater rate of l-naphthol conjugation in both unactivated and activated microsomes than renal microsomes prepared in phosphate buffers alone. Preparation of hepatic microsomes with or without 0.25M sucrose had no effect on UDP-glucuronyltransferase activity. Unactivated (-deoxycholate) renal enzyme was activated when incubations were done at a low pH (5.7), whereas fully activated (0.03% deoxycholate) renal microsomal UDP-glucuronyltransferase displayed a pH optimum at 6.5. Renal microsomal UDP-glucuronyltransferase activity toward l-naphthol, p-nitrophenol and 4-methylumbelliferone was induced by pretreatment of rats with beta-naphthoflavone and trans-stilbene oxide but not by phenobarbital or 3-methylcholanthrene. These data demonstrate that renal UDP-glucuronyltransferases are different from the hepatic enzymes with regard to biochemical properties, substrate specificity and in response to chemical inducers of xenobiotic metabolism. 相似文献
10.
Cholesterol-dependent modification of microsomal dynamics and UDPglucuronyltransferase kinetics 总被引:1,自引:0,他引:1
The effect of both in vitro incorporation and removal of cholesterol in guinea pig liver microsomes on the lipid composition, dynamic properties of the membrane, and kinetic constants of UDPglucuronyltransferase was studied. No significant changes either in the fatty acid composition or in the distribution of phospholipid classes were observed upon cholesterol incorporation and removal. Lateral and rotational mobility measured by the efficiency of pyrene excimer formation and fluorescence of 1,6-diphenylhexatriene decreased with cholesterol incorporation and increased in parallel to cholesterol removal. These changes were associated with alterations in the kinetic properties of UDPglucuronyltransferase. Whereas Vmax increased, the Km of the different steps of the reaction decreased with cholesterol incorporation. The negative homotropic effect and apparent cooperativity of UDP-glucuronic acid decreased when cholesterol was incorporated and increased after cholesterol removal. Moreover, the UDP-N-acetylglucosamine-dependent activation of the enzyme decreased in correlation with an increase of cholesterol concentration in microsomes. It has been demonstrated that both the shift of the non-Michaelian kinetics of the enzyme to Michaelian and the decrease of the UDP-N-acetylglucosamine-dependent activation of the enzyme are evoked by a change of the physical state of the UDPglucuronyltransferase milieu from a gel phase to a liquid-crystalline phase. Therefore, we must admit that cholesterol incorporation in the microsomes while producing an increased packing of the bulk lipids would also cause the separation of more fluid phospholipids, which increase the proportion of molecules in the liquid-crystalline state within the enzyme environment. 相似文献
11.
The congenitally jaundiced Gunn rat does not conjugate bilirubin but does conjugate bilirubin dimethyl diester. Partial defects in conjugating p-nitrophenol and demethylating aminopyrine are also evident. A proposed mechanism to explain this combination of findings is a defective microsomal membrane. To examine the 'matrix' of Gunn microsomal membranes, hepatic microsomes were isolated from Gunn (jj) and outbred Wistar (JJ) rats and were studied by electron paramagnetic resonance spectroscopy of 7-doxylstearic and 12-doxylstearic acid probes, fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene, glucose-6-phosphatase activity vs. temperature, and lipid analysis. The data indicate several factors related to lipid bilayer order do not differ in microsomes from jj and JJ. 相似文献
12.
N Tavoloni M J Jones L M Isola P D Berk 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1984,176(4):356-365
These studies were carried out to determine whether bovine serum albumin (BSA), which is usually included in the incubation mixture for the in vitro determination of bilirubin-UDP-glucuronyl transferase (GT) activity, affects GT activity. Using bilirubin as substrate, addition of BSA to the enzyme reaction mixture at concentrations varying from 2 to 30 mg/ml resulted in a dose-related inhibition of "native" GT activity of rat liver microsomes. When detergent-activated enzyme was employed, increasing concentrations of BSA also required higher concentrations of deoxycholate, digitonin, or Triton X-100 to produce maximal bilirubin conjugation. Low BSA concentrations (2 mg/ml) prevented enzyme activation by both detergents and UDP-N-acetyl glucosamine. When BSA was omitted and bilirubin dissolved in dimethyl sulfoxide, UDP-N-acetyl glucosamine failed to enhance GT activity, and activation by detergents was only 15-25% of that observed in the presence of optimal concentrations of BSA. When rat albumin was substituted for BSA, a similar dose-related inhibition of in vitro bilirubin conjugation by untreated microsomes was observed, although at any given albumin concentration, GT activity was lower with rat than with bovine albumin. Additionally, both detergents and UDP-N-acetyl glucosamine produced similar GT activation regardless of the rat albumin concentration. Finally, these effects of BSA and rat albumin could not be reproduced when beta-lactoglobulin was employed and/or when p-nitrophenol was the acceptor substrate of GT. These findings indicate that albumin, in particular BSA, profoundly and selectively influences the in vitro activity of microsomal GT toward bilirubin as the acceptor substrate. 相似文献
13.
UDP-glucuronosyltransferase- (UGT-) dependent glucuronidation is an important detoxification process for many endogenous and exogenous compounds in mammals. Treatment of rat hepatic microsomes with the reducing reagent dithiothreitol (DTT) resulted in a significant increase in p-nitrophenol (p-NP) glucuronidation in a time- and concentration-dependent manner. The DTT-dependent activation of glucuronidation was specific for planar phenols but not for bilirubin or testosterone without membrane perturbation of the microsomes. p-NP glucuronidation in Gunn rat hepatic microsomes lacking UGT1 isozymes was not affected by DTT, indicating that UGT1A6 in the microsomes is mainly involved in the activation. The DTT-dependent activation was inhibited by 1,6-bis(maleimido)hexane (BMH) but not by N-ethylmaleimide, indicating that cross-linking between cysteine residues in UGT1A6 is responsible for the activation. Immunoblot analysis of rat hepatic microsomes on nonreducing SDS-PAGE gels revealed that most of the UGT1A6 migrated as a monomer, suggesting that DTT could affect an intramolecular disulfide bond in the UGT1A6 that may be responsible for the activation. To identify which of the ten cysteines in UGT1A6 are involved in the disulfide bond, rat UGT1A6 wild type and a set of mutants, each with a cysteine to serine substitution, were constructed and expressed in COS cells. Treatment of COS microsomes with DTT had no effect on the activity of the wild type but BMH showed significant inhibition, suggesting that UGT1A6 expressed in COS cells may be in the reduced and activated state. Replacement of either Cys 121 or Cys 125 with serine showed insensitivity to the BMH-dependent inhibition. These results demonstrate that both Cys 121 and Cys 125 are responsible for the activation of the activity through the disulfide bond in rat UGT1A6. 相似文献
14.
Kelmer-Bracht AM Santos CP Ishii-Iwamoto EL Broetto-Biazon AC Bracht A 《Biochimica et biophysica acta》2003,1638(1):50-56
According to previous reports, adjuvant-induced arthritic rats present reduced activities of the hepatic glucose 6-phosphatase. A kinetic study was done in order to characterize this phenomenon. Microsomes were isolated from livers of arthritic and control rats (Holtzman strain) and the glucose 6-phosphatase was measured at various temperatures (13-37 degrees C) and glucose 6-phosphate concentrations. Irrespective of the temperature, the enzyme from arthritic rats presented a reduction of both V(max) and K(M). Detergent treatment of liver microsomes from control rats increased the activity, but no increase was found when microsomes from arthritic rats were treated in the same way. The mannose 6-phosphatase activity of detergent-treated microsomes from arthritic rats was only 25% of the activity found with detergent-treated microsomes from control rats. Without detergent treatment, the mannose 6-phosphatase activities of both control and arthritic rats were minimal. The activation energy, derived from V(max), was not changed by arthritis. In vivo arthritic rats presented higher hepatic glucose 6-phosphate concentrations, a phenomenon that is consistent with a reduced activity of glucose 6-phosphatase. It was concluded that in arthritic rats, the hydrolase is probably reduced, without a similar change in the translocase activity. 相似文献
15.
The mechanism of activation of hepatic microsomal glucose-6-phosphatase (EC 3.1.3.9) in vitro by amiloride has been investigated in both intact and fully disrupted microsomes. The major effect of amiloride is a 4.5-fold reduction in the Km of glucose-6-phosphatase activity in intact diabetic rat liver microsomes. Amiloride also decreased the Km of glucose-6-phosphatase activity in intact liver microsomes isolated from starved rats 2.5-fold. Kinetic calculations, direct enzyme assays and direct transport assays all demonstrated that the site of amiloride action was T1, the hepatic microsomal glucose 6-phosphate transport protein. This is, to our knowledge, the first report of an activation of any of the proteins of the multimeric hepatic microsomal glucose-6-phosphatase complex. 相似文献
16.
A D Mottino J M Pellegrino E E Guibert M G Roma E A Rodríguez Garay 《The International journal of biochemistry》1988,20(10):1113-1116
1. Bilirubin UDP-glucuronyltransferase activity and its dependence on substrate concentrations in rat liver, renal cortex and intestinal mucosa microsomes were studied. 2. Bilirubin monoglucuronide synthesis from unconjugated bilirubin was a higher capacity, lower affinity step in comparison with bilirubin diglucuronide formation in the three tissues tested. 3. Bilirubin glucuronide formation in liver microsomes showed a higher capacity but a lower affinity than extrahepatic ones. Renal cortex and intestinal mucosa exhibited similar kinetics parameters. 4. In vitro bilirubin glucuronidation in renal cortex and intestinal mucosa was quantitatively important as compared with the hepatic one. 相似文献
17.
大鼠再生肝抗CCl4损伤与其线粒体呼吸活性变化的关系 总被引:4,自引:2,他引:2
本工作观察了肝部分切除(68%)后96h 大鼠再生肝的抗 CCl_4损伤作用,并用氧电极法测定了再生肝线粒体的呼吸活性。结果如下: (1)CCl_4(50%,10ml/kg)引起的动物死亡率,肝切除组大鼠较假手术组明显降低;(2)CCl_4(50%,5 ml/kg)损伤后,肝切除组大鼠血清胆红素、血清谷丙转氨酶(sGPT)均明显低于假手术组,组织学检查损伤程度也明显减轻;(3)无论是否伴有 CCI_1损伤,肝切除组大鼠肝线粒体的呼吸活性均强于假手术组,且肝线粒体呼吸活性的变化与血清胆红素、sGPT 及肝组织损伤程度的改善是一致的。上述结果提示:再生肝线粒体呼吸活性增高,同时不易受 CCl_4损伤,可能在再生肝抗 CCl_4损伤机制中起一定作用。 相似文献
18.
The differences in the levels of cytochrome P-450s in hepatic and renal microsomes between spontaneously hypertensive rats (SHR) and normotensive control rats (Wistar Kyoto rats, WKY) were investigated by Western blotting with a specific antibody. Differences in the metabolic activity of the microsomes were also studied. In hepatic microsomes, the content of P450 PB-1 (IIIA2) was 140% higher in SHR than in WKY and the content of P450 IF-3 (IIA1) in SHR was one-seventh that in WKY. The differences reflected the increase in testosterone 6 beta-hydroxylation activity and decrease in testosterone 7 alpha-hydroxylation activity in hepatic microsomes of SHR. The level of P450 K-5 (IVA2) in hepatic microsomes of SHR was 4-times that in microsomes of WKY. The levels of other cytochrome P-450s in SHR were not very different from those in WKY. In renal microsomes, the levels of three renal cytochrome P-450s, P450 K-2, K-4, and K-5, were measured. The level of P450 K-5 (fatty acid omega-hydroxylase) in SHR was 50% higher than that in WKY and the difference reflected the increase in lauric acid omega- and (omega-1)-hydroxylation activities of the renal microsomes of SHR. The levels of P450 K-2 and K-4 did not differ in both rats. 相似文献
19.
A comparison of the kinetic properties of two different forms of microsomal UDPglucuronyltransferase
Two forms of UDPglucuronyltransferase (EC 2.4.1.17) have been purified from microsomes of pig liver. One form is free of phospholipids and the other contains a small amount of residual phospholipids. Each form, however, is responsive to activation on addition of purified phospholipids. Comparison of kinetic properties of these enzymes, after reconstitution with identical phospholipid environments, indicate that these are unique functional forms of UDPglucuronyltransferase. The two differ by as much as 100-fold in their rates of conjugation at Vm of p-nitrophenol. Relative rates of glucuronidation of a variety of phenolic aglycones are different for the two enzymes, which suggests different reaction mechanisms. The energetic basis for binding of UDP-glucuronic acid to the active sites is different for the two forms of UDPglucuronyltransferase. Moreover, one form, but not the other, binds Mn2+, which leads to modulation of kinetic properties. 相似文献
20.
Inhibition of CCl4 metabolism by oxygen varies between isoenzymes of cytochrome P-450 总被引:1,自引:0,他引:1
R F Burk K E Hill J M Lane 《Biochemical and biophysical research communications》1988,152(3):1463-1467
Oxygen inhibition of CCl4 metabolism by different isoenzymes of cytochrome P-450 was assessed by studying liver microsomes isolated from control rats and rats treated with phenobarbital or isoniazid. Rates of CCl4 metabolism were similar for all microsomes under a nitrogen atmosphere. An air atmosphere inhibited metabolism by microsomes from control rats to 12% of the value under nitrogen and metabolism by microsomes from rats treated with phenobarbital to 5%. It inhibited metabolism by microsomes from rats treated with isoniazid only to 32%. Rats treated with phenobarbital, which increases hepatic cytochrome P-450 content, or isoniazid, which does not increase hepatic cytochrome P-450 content, both metabolized more CCl4 than control rats as indicated by exhalation of greater quantities of CCl4 metabolites and by an increase in CCl4 toxicity. These results indicate that some isoenzymes of cytochrome P-450 are more effective than others in metabolizing CCl4 when oxygen is present. 相似文献