scholarly journals Light-dependent cytochrome P-450 changes in mung beans (Phaseolus aureus)

1981 ◽  
Vol 196 (3) ◽  
pp. 825-829 ◽  
Author(s):  
G A F Hendry ◽  
J D Houghton ◽  
O T G Jones
Keyword(s):  
Doubling Time ◽  
Rapid Decrease ◽  
Half Time ◽  
Phaseolus Aureus ◽  
Microsomal Cytochrome ◽  
Cytochrome P 450

Maximum concentrations of microsomal cytochrome P-450 are present in 3-4 day-old mung beans (Phaseolus aureus). On illumination of dark-grown seedlings, cytochrome P-450 and later cytochrome P-450 undergo a rapid decrease in concentration in vivo, with an apparent half-time of about 6 h. Conversely light-grown seedlings, transferred to darkness, show a slow accumulation of cytochrome P-450, doubling time of about 30 h, with a later accumulation of cytochrome P-420. Microsomal cytochromes b559, b560.5 and b562.5 do not significantly alter on light-dark transitions. Possible functions for dark-induced cytochrome P-450 are discussed.

scholarly journals Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats

1991 ◽  
Vol 280 (2) ◽  
pp. 373-377 ◽  
Author(s):  
S Dueland ◽  
J Reichen ◽  
G T Everson ◽  
R A Davis
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Liver Function ◽  
Urinary Excretion ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Microsomal Cytochrome ◽  
Duct Ligation ◽  
Cytochrome P 450

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.

Cytochrome P-450 and Peroxidase Oxidize Detoxication Products of Carcinogenic Aristolochic Acids (Aristolactams) to Reactive Metabolites Binding to DNA in vitro

1995 ◽  
Vol 60 (12) ◽  
pp. 2189-2199 ◽  
Author(s):  
Marie Stiborová ◽  
Eva Frei ◽  
Heinz H. Schmeiser ◽  
Manfred Wiessler
Keyword(s):  
Dna Adducts ◽  
Microsomal Cytochrome ◽  
Aristolochic Acids ◽  
Nuclease P1 ◽  
Order Of Magnitude ◽  
Prostaglandin H ◽  
Cytochrome P 450

We report the analysis of DNA adducts formed from aristolactams I and II, which are the final metabolites derived from carcinogenic aristolochic acids in vivo, after their oxidation by microsomal cytochrome P-450 and horseradish peroxidase in vitro. DNA adducts were detected and quantified using the nuclease P1-enhanced variation of the 32P-postlabeling assay. Quantitative analysis revelead that the extent of modification of DNA by aristolactams activated by peroxidase was more than one order of magnitude higher than for activation by microsomal cytochrome P-450. Peroxidase catalyzes the formation of active oxygen in the presence of NADH, H2O2 and aristolactams. Aristolactams are also oxidized by mammalian peroxidase prostaglandin H synthase. The possible role of aristolactams in carcinogenesis induced by aristolochic acid is discussed.

scholarly journals Metabolic activation of acetylenic substituents to derivatives in the rat causing the loss of hepatic cytochrome P-450 and haem

1978 ◽  
Vol 174 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Ian N. H. White
Keyword(s):  
Covalent Binding ◽  
Metabolic Activation ◽  
Microsomal Protein ◽  
Significant Loss ◽  
Microsomal Cytochrome ◽  
Rf Values ◽  
Green Pigments ◽  
Cytochrome P 450

1. A number of acetylenic-substituted steroidal and non-steroidal compounds, including 2,2-dipropargylacetamide, pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol (Danazol) and acetylene gas, when administered to rats in vivo brought about a decrease in the concentrations of hepatic microsomal cytochrome P-450 and haem. Abnormal haem-breakdown products, ‘green pigments’, and porphyrins accumulated in the livers of these animals. 2. For loss of microsomal cytochrome P-450 to occur in vitro, metabolic activation of the acetylenic substituent was necessary. The enzyme system responsible required NADPH and air, and was induced by pretreatment of rats with phenobarbitone; these are characteristics typical of the microsomal mixed-function oxidases. 3. When rats were dosed with 17α-ethynyl-17β-hydroxyandrost-4-en-3-one (ethynyltestosterone, 1mmol/kg) the pattern of green pigments extracted from the liver 4h after dosing and separated by t.l.c. was quite different from that in rats given 17β-hydroxy-17α-vinylandrost-4-en-3-one (vinyltestosterone), suggesting that reduction of the unsaturated triple bond to a double bond is not normally part of the metabolic activation pathway of the acetylenic substituent. 4. The green pigments extracted from the livers of rats 4h after the administration of the acetylenic-substituted compounds (1mmol/kg) when separated by silica-gel t.l.c. had variable RF values. The number and distribution of green pigments was characteristic for each compound examined. There was little correlation between the total loss of hepatic microsomal haem and the apparent intensity of the green pigments seen on the thin-layer chromatograms. 5. After incubation of [14C]acetylene in vitro with microsomal preparations from phenobarbitone-pretreated rats and a NADPH-generating system, no significant covalent binding to microsomal protein was detected over a 30min incubation period, although under similar conditions there was a significant loss of cytochrome P-450.

scholarly journals Fractionation and purification of hepatic microsomal cytochrome P-450 isoenzymes from phenobarbital-pretreated rats by h.p.l.c. A convenient tool for screening of isoenzymes inactivated by allylisopropylacetamide

1986 ◽  
Vol 239 (3) ◽  
pp. 661-669 ◽  
Author(s):  
L M Bornheim ◽  
M A Correia
Keyword(s):  
Ion Exchange ◽  
Column Chromatography ◽  
Resolving Power ◽  
Isolation And Purification ◽  
Microsomal Cytochrome ◽  
Promising Tool ◽  
Ion Exchange Column ◽  
Membrane Bound ◽  
Cytochrome P 450

A procedure incorporating the salient features of ion-exchange column chromatography with ion-exchange h.p.l.c. is described for the fractionation and purification to homogeneity of several membrane-bound rat hepatic phenobarbital (PB)-inducible cytochrome P-450 isoenzymes, including the major PB-inducible species. The resolving power of this technique makes it a highly promising tool for the isolation and purification of closely related cytochrome P-450 isoenzymes. In addition, it may also be used for screening of individual isoenzymes either selectively induced or repressed by a variety of endobiotics or xenobiotics. Accordingly, we have exploited this particular feature to identify not only the PB-inducible cytochrome P-450 isoenzymes destroyed in vivo by allylisopropylacetamide, a suicide inactivator of cytochrome P-450, but also to distinguish those that are reparable by exogenous haemin from those that are irreparably damaged.

scholarly journals Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism

1986 ◽  
Vol 238 (3) ◽  
pp. 871-878 ◽  
Author(s):  
A G Smith ◽  
J E Francis ◽  
S J E Kay ◽  
J B Greig ◽  
F P Stewart
Keyword(s):  
Additional Treatment ◽  
Mechanistic Studies ◽  
Iron Species ◽  
Uroporphyrinogen Decarboxylase ◽  
Microsomal Cytochrome ◽  
Hepatic Microsomes ◽  
Iron Treatment ◽  
Maximum Inhibition ◽  
Cytochrome P 450

Porphyria was induced in C57BL/10 mice with iron overload by a single oral dose (100 mg/kg) of hexachlorobenzene (HCB). Within 2 weeks hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was inhibited, reaching a maximum (greater than 95%) at 6-8 weeks. There was no recovery by 14 weeks, despite a fall in liver HCB concentrations to only 6% of the day-3 value. The major rise in hepatic porphyrin levels occurred after 4 weeks and secondary inhibition of uroporphyrinogen synthase (EC 4.2.1.75) was inferred from the progressively greater proportion of uroporphyrin I present relative to the III isomer. Plasma alanine aminotransferase (EC 2.6.1.2) activity was also elevated. Although, in further studies, total microsomal cytochrome P-450 content and ethoxyphenoxazone de-ethylase activity reached a peak a few days after dosing and had declined significantly at the time of maximum inhibition of the decarboxylase, additional treatment of HCB-dosed mice with a cytochrome P1-450 inducer, beta-naphthoflavone, enhanced the inhibition, whereas piperonyl butoxide, an inhibitor of cytochrome P-450, partially protected. Uroporphyrinogen decarboxylase was not radiolabelled in vivo by [14C]HCB. There was no major difference in the ability to hydroxylate HCB between hepatic microsomes from induced C57BL/10 mice and those from the insensitive DBA/2 strain. By contrast, lipid peroxidation, in the presence of NADPH, was 8-fold greater in control C57BL/10 microsomes than in DBA/2 microsomes and was stimulated by iron treatment (although not by HCB). The results suggest that the inhibition of hepatic uroporphyrinogen decarboxylase is unlikely to be due to a direct effect of a metabolite of HCB but to another process requiring a specific cytochrome P-450 isoenzyme and an unknown iron species.

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