The metabolism of drugs by hepatic microsomal enzymes. Studies on intramicrosomal distribution of enzymes and relationships between enzyme activity and structure of the hepatic endoplasmic reticulum

1966 ◽  
Vol 5 (5) ◽  
pp. 475-490 ◽  
Author(s):  
James R. Fouts ◽  
Larry A. Rogers ◽  
Theodore E. Gram
Keyword(s):  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Microsomal Enzymes ◽  
Hepatic Microsomal Enzymes

Elevation of Serum Triacylglycerol Concentration in Association with Hepatic Microsomal Enzyme Induction after Treatment with Phenylbutazone and Diclofenac Sodium in Rats

1993 ◽  
Vol 84 (4) ◽  
pp. 387-390 ◽  
Author(s):  
Mahmoud M. Farag ◽  
Amel T. Hassib
Keyword(s):  
Adverse Effect ◽  
Enzyme Activity ◽  
Diclofenac Sodium ◽  
Microsomal Enzyme ◽  
Microsomal Enzymes ◽  
Hepatic Microsomal Enzyme ◽  
Triacylglycerol Concentration ◽  
The Relationship ◽  
Microsomal Enzyme Induction ◽  
Hepatic Microsomal Enzymes

1. The relationship between serum triacylglycerol concentration and hepatic microsomal enzyme activity was examined in rats. 2. Two groups of rats were injected with diclofenac sodium at doses of 2.5 and 5 mg day−1 kg−1. A third group was injected with phenylbutazone at a dose of 20 mg day−1 kg−1. The treatment was continued for 15 days and the rats were killed 24 h after the last dose. 3. In all drug-treated rats, the serum triacylglycerol concentration and the hepatic microsomal activities of aminopyrine N-demethylase and aniline hydroxylase were significantly increased as compared with the corresponding values in control rats. The correlations between the serum triacylglycerol concentrations and the activities of the two enzymes, as indices of the hepatic microsomal activity, were highly significant. 4. These results indicate that the possibility of hypertriglyceridaemia as an adverse effect of the induction of the hepatic microsomal enzymes after the administration of phenylbutazone and diclofenac sodium should be considered.

Morphological and biochemical analyses of changes in rat hepatocytes related to wine and ethanol consumption

1984 ◽  
Vol 42 ◽  
pp. 232-233
Author(s):  
S.M. Geyer ◽  
C.L. Mendenhall ◽  
J.T. Hung ◽  
E.L. Cardell ◽  
R.L. Drake ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Malic Enzyme ◽  
Smooth Endoplasmic Reticulum ◽  
Rat Hepatocytes ◽  
Mature Male ◽  
Treatment Groups ◽  
Malic Enzyme Activity ◽  
Biochemical Analyses

Thirty-three mature male Holtzman rats were randomly placed in 3 treatment groups: Controls (C); Ethanolics (E); and Wine drinkers (W). The animals were fed synthetic diets (Lieber type) with ethanol or wine substituted isocalorically for carbohydrates in the diet of E and W groups, respectively. W received a volume of wine which provided the same gram quantity of alcohol consumed by E. The animals were sacrificed by decapitation after 6 weeks and the livers processed for quantitative triglycerides (T3), proteins, malic enzyme activity (MEA), light microscopy (LM) and electron microscopy (EM). Morphometric analysis of randomly selected LM and EM micrographs was performed to determine organellar changes in centrilobular (CV) and periportal (PV) regions of the liver. This analysis (Table 1) showed that hepatocytes from E were larger than those in C and W groups. Smooth endoplasmic reticulum decreased in E and increased in W compared to C values.

scholarly journals Regulation of glucocorticoid receptor function and angiotensin-converting enzyme activity

1997 ◽  
Vol 43 (4) ◽  
pp. 51-54
Author(s):  
P. P. Golikov
Keyword(s):  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Glucocorticoid Receptors ◽  
Converting Enzyme ◽  
Receptor Function ◽  
Angiotensin Converting Enzyme Activity ◽  
Mammalian Tissues ◽  
Shock Proteins ◽  
Convoluted Tubules ◽  
Direct Biosynthesis

The central link in the mechanism of action of glucocorticoids is specific cytoplasmic glucocorticoid receptors (GH). Their synthesis is programmed by 1 gene of chromosome 5 [44]. The direct biosynthesis of GR occurs in the endoplasmic reticulum of the cytoplasm [12]. In the cytoplasm, GRs bind to heat shock proteins (HSP, chaperone proteins) mol. mass of 50, 70, 90 kD [20, 59]. Like the mass of the GR – HSP complex is 300 kD [14]. In the absence of glucocorticoids, GRs are localized mainly in the cytoplasm [30, 63]. In 1 cell contains from 5000 to 100 000 specific GH. GRs have been found in many mammalian tissues [13], however, certain tissues do not contain GRs: the intermediate pituitary, Kupffer and endothelial cells of the liver, renal glomeruli, and proximal convoluted tubules [12, 31].

Treatment of mammalian cells with the endoplasmic reticulum-proliferator compactin strongly induces recombinant and endogenous xenobiotic metabolizing enzymes and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro

1999 ◽  
Vol 112 (4) ◽  
pp. 515-523
Author(s):  
L. McLaughlin ◽  
B. Burchell ◽  
M. Pritchard ◽  
C.R. Wolf ◽  
T. Friedberg
Keyword(s):  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Metabolizing Enzymes ◽  
P450 Reductase ◽  
Coa Reductase

Some xenobiotics induce membrane-bound drug metabolizing enzymes (Xme) and a profound proliferation of the endoplasmic reticulum (ER) in vivo. However these effects are much weaker in vitro, possibly due to absence of certain transcription factors. We tested the possibility that ER proliferation can affect the level of ER-resident enzymes even in the absence of transcriptional activation. For this purpose we analysed the effects of compactin, which has been shown to induce ER proliferation in vitro, on recombinant Xme, which were expressed from a constitutive viral promoter. High levels of recombinant UDP-glucuronosyltransferase UGT1A6 were achieved by amplification of the UGT1A6 cDNA using the dihydrofolate reductase cDNA as selectable marker in DHFR- CHO cells. Treatment of the resulting cell lines with lipoprotein-deficient serum in the absence and presence of compactin for 5 days resulted in a 1.3- and 2.3-fold, respectively, increase of the UGT enzyme activity towards 4-methylumbelliferone, paralleled by an induction of immunoreactive UGT1A6 protein. Similarly, treatment with this 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor increased the endogenous P450 reductase activity 2.6-fold, concomitant with an increase of immunodetectable protein. As expected compactin induced the level of 3-hydroxy-3-methylglutaryl-CoA reductase. Increased levels of this protein have been associated with a proliferation of the ER. Compactin treatment of a separate cell line that expressed recombinant human P450 reductase increased this enzyme activity fivefold. Pulse-chase experiments revealed that the induction of the recombinant Xme by compactin was most likely due to decreased protein degradation. Our results show that enzyme systems unrelated to those involved in cholesterol biosynthesis are affected by compounds known to affect membrane biogenesis. Since this effect extends to heterologously expressed enzymes, it also provides an efficient means by which to increase the levels of recombinant ER proteins.

scholarly journals Induction of Hepatic Microsomal Enzymes after Brief Administration of Rifampicin in Man

1977 ◽  
Vol 72 (5) ◽  
pp. 924-926 ◽  
Author(s):  
J.P. Miguet ◽  
P. Mavier ◽  
C.J. Soussy ◽  
D. Dhumeaux
Keyword(s):  
Microsomal Enzymes ◽  
Hepatic Microsomal Enzymes
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