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Cyp2d3  -  cytochrome P450, family 2, subfamily d,...

Rattus norvegicus

Synonyms: CYPIID3, Cyp2d-3, Cyp2d13, Cyp2d6, Cytochrome P450 2D3, ...
 
 
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High impact information on Cyp2d13

  • The intensity of this band was significantly correlated with debrisoquine 4-hydroxylase activity when liver microsomes from 44 organ donors were examined [1].
  • Debrisoquine 4-hydroxylase activity is a prototype for genetic polymorphism in oxidative drug metabolism in humans; approximately 10% of Caucasian populations exhibit the poor metabolizer phenotype, and the clearance of at least 14 other drugs has been shown to be deficient in patients exhibiting this phenotype [1].
  • Genetic polymorphism in oxidative drug metabolism is perhaps best exemplified in the case of debrisoquine 4-hydroxylase activity, where the incidence of deficient metabolism ranges from 1% to 30% in various populations and this defect is also linked to an impaired ability to metabolize a number of other drugs effectively [2].
  • However, we found that [3H]mepyramine labeled not only the H1 receptor but also a [3H]mepyramine binding protein (MBP) in the liver, which protein appears to be related to the subfamily of debrisoquine 4-hydroxylase (cytochrome P450IID) isozymes [3].
  • Propranolol and quinidine, specific inhibitors of debrisoquine 4-hydroxylase, markedly inhibited lidocaine 3-hydroxylase activity of Wistar male rats, but not N-deethylase activity [4].
 

Biological context of Cyp2d13

  • There is also a major sex difference in debrisoquine 4-hydroxylase activity of all three strains [5].
  • Amino acid sequences of twelve tryptic peptides derived from MBP are highly homologous with those of rat debrisoquine 4-hydroxylase (cytochrome P450 2D1) and other rat P450 2D subfamily members [6].
 

Associations of Cyp2d13 with chemical compounds

  • Debrisoquine 4-hydroxylase activity was inducible by both 3-methylcholanthrene and phenobarbital in DA and Fischer rats [5].
  • Quinine and quinidine showed 400 and 80 times, respectively, higher affinity for MBP than for debrisoquine 4-hydroxylase [6].
  • These results suggest the selective impairment of debrisoquine 4-hydroxylase by propranolol pretreatment [7].
  • When preincubated with rat liver microsomes, the antibody against the final P-450 BTL preparation suppressed bunitrolol and debrisoquine 4-hydroxylase activities dose-dependently and almost completely [8].
  • This was achieved using established diagnostic probes (O-dealkylation of methoxy-, ethoxy- and pentoxy-resorufin, testosterone 2alpha-hydroxylase, debrisoquine 4-hydroxylase, aniline p-hydroxylase and lauric acid hydroxylase) and immunologically using Western blotting [9].
 

Analytical, diagnostic and therapeutic context of Cyp2d13

  • Repetitive oral administration of imipramine (100 mg/kg/day for 5 days) caused a decrease in rat liver microsomal debrisoquine 4-hydroxylase activity, a characteristic reaction catalyzed by cytochrome P450 (CYP) 2D1 [10].

References

  1. Characterization of a human liver cytochrome P-450 involved in the oxidation of debrisoquine and other drugs by using antibodies raised to the analogous rat enzyme. Distlerath, L.M., Guengerich, F.P. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  2. Purification and characterization of the rat liver microsomal cytochrome P-450 involved in the 4-hydroxylation of debrisoquine, a prototype for genetic variation in oxidative drug metabolism. Larrey, D., Distlerath, L.M., Dannan, G.A., Wilkinson, G.R., Guengerich, F.P. Biochemistry (1984) [Pubmed]
  3. Does the [3H]mepyramine binding site represent the histamine H1 receptor? Re-examination of the histamine H1 receptor with quinine. Liu, Q., Horio, Y., Fujimoto, K., Fukui, H. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  4. Metabolic activation of lidocaine and covalent binding to rat liver microsomal protein. Masubuchi, Y., Araki, J., Narimatsu, S., Suzuki, T. Biochem. Pharmacol. (1992) [Pubmed]
  5. Sex and strain differences in hepatic debrisoquine 4-hydroxylase activity of the rat. Kahn, G.C., Rubenfield, M., Davies, D.S., Murray, S., Boobis, A.R. Drug Metab. Dispos. (1985) [Pubmed]
  6. Purification and characterization of [3H]mepyramine (histamine H1 antagonist)-binding protein from rat liver: a highly homologous protein with cytochrome P450 2D. Fukui, H., Mizuguchi, H., Liu, Y.Q., Wang, N.P., Hayashi, H., Kangawa, K., Wakamiya, T., Leurs, R., Shiba, T., Matsuo, H. J. Biochem. (1995) [Pubmed]
  7. Impairment of debrisoquine 4-hydroxylase and related monooxygenase activities in the rat following treatment with propranolol. Masubuchi, Y., Fujita, S., Chiba, M., Kagimoto, N., Umeda, S., Suzuki, T. Biochem. Pharmacol. (1991) [Pubmed]
  8. Purification and characterization of a cytochrome P-450 isozyme catalyzing bunitrolol 4-hydroxylation in liver microsomes of male rats. Suzuki, T., Narimatsu, S., Fujita, S., Masubuchi, Y., Umeda, S., Imaoka, S., Funae, Y. Drug Metab. Dispos. (1992) [Pubmed]
  9. Stability of cytochrome P450 proteins in cultured precision-cut rat liver slices. Hashemi, E., Till, C., Ioannides, C. Toxicology (2000) [Pubmed]
  10. Inhibition and induction of cytochrome P450 isozymes after repetitive administration of imipramine in rats. Masubuchi, Y., Takahashii, C., Fujio, N., Horie, T., Suzuki, T., Imaoka, S., Funae, Y., Narimatsu, S. Drug Metab. Dispos. (1995) [Pubmed]
 
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