Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that Murphy-Sturm lymphosarcoma-bearing rats have significantly decreased hepatic microsomal cytochrome P-450 and NADPH-cytochrome c reductase activity, a consequent decreased capacity for oxidative microsomal drug metabolism, and increased microsomal heme oxygenase activity. Splenic microsomes obtained from tumor-bearing rats did not display similar changes. To define the cellular locus of these changes, preparations of hepatic parenchymal and hepatic sinusoidal cells were obtained from control and Murphy-Sturm lymphosarcoma-bearing rats and examined for alterations in microsomal parameters of drug metabolism and heme oxygenase. In hepatic parenchymal cell populations, heme oxygenase activity was significantly increased in tumor-bearing rats (0.046 nmol/mg/min vs. 0.019 nmol/mg/min, control, p less than 0.01) while other microsomal parameters were all significantly decreased in activity (cytochrome P-450, 0.25 nmol/mg vs 0.70 nmol/mg, control, p less than 0.001; NADPH-cytochrome c reductase, 24.4 nmol/mg/min vs 42.6 nmol/mg/min, control, p less than 0.005; benzo(a) pyrene hydroxylase, 0.230 nmol/mg/min vs. 0.518 nmol/mg/min, control, p less than 0.001). These results are similar to those obtained with microsomes from whole liver. Conversely, while hepatic sinusoidal cell preparations also demonstrated increased heme oxygenase activity (0.134 nmol/mg/min vs 0.079 nmol/mg/min, control, p less than 0.01), all other hepatic sinusoidal cell microsomal parameters were not appreciably altered in tumor-bearing animals. The results indicate that the major effect of the tumor-bearing state on hepatic microsomal heme and drug metabolism is on the parenchymal cell, and not the sinusoidal cell population.
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PMID:Alterations in microsomal drug metabolism and heme oxygenase activity in isolated hepatic parenchymal and sinusoidal cells in Murphy-Sturm lymphosarcoma-bearing rats. 309 26

Previous studies have shown that tumor-bearing rats have significantly decreased hepatic microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity with, consequently, significantly decreased capacity for microsomal oxidative drug metabolism. Subsequent investigations have revealed that the rates of hepatic cytochrome P-450 apo-protein synthesis and degradation are decreased significantly and hepatic microsomal heme oxygenase activity is increased significantly in rats bearing an extra-hepatic tumor. Further studies have been done to attempt to clarify the pathogenesis and significance of these observations. Hepatic delta-aminolevulinic acid (ALA) synthetase activity in male Wistar rats declined to a nadir of 162 +/- 34 (S.E.) pmoles ALA per mg protein per 30 min 6 days following i.m. transplantation of Murphy-Sturm lymphosarcoma (vs control = 218 +/- 36 pmoles per mg per 30 min). Turnover of 3H-labeled heme in microsomal CO-binding particles (i.e. cytochrome P-450 heme) was increased significantly 8 days following i.m. transplantation of Murphy-Sturm lymphosarcoma with a T 1/2 of 5.5 hr for the fast phase of hepatic cytochrome P-450 heme disappearance in tumor-bearing rats as compared with a T 1/2 of 7 hr in control rats. Hepatic cytochrome P-450 apo-protein concentration was slightly, but not significantly, increased in Murphy-Sturm lymphosarcoma-bearing rats as compared with control rats up to 10 days following tumor transplantation. These results suggest that, in Murphy-Sturm lymphosarcoma-bearing rats, decreased microsomal cytochrome P-450 concentration is the result of both decreased cytochrome P-450 apo-protein synthesis and increased cytochrome P-450 heme turnover. Apo-cytochrome P-450 concentration was not appreciably altered because increased cytochrome P-450 heme turnover and decreased cytochrome P-450 apo-protein degradation were balanced by decreased cytochrome P-450 apo-protein synthesis. Because of their effects on cytochrome P-450 concentration and action, these alterations in heme and hemoprotein metabolism may be of importance in regulating oxidative drug metabolism in the tumor-bearing state.
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PMID:Alterations in hepatic heme and cytochrome P-450 metabolism in Murphy-Sturm lymphosarcoma-bearing rats. Implications for drug metabolism. 654 78