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Gene Review

CYP2B7P  -  cytochrome P450, family 2, subfamily B,...

Homo sapiens

Synonyms: CYP2B, CYP2B7, CYP2B7P1
 
 
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Disease relevance of CYP2B7P1

 

High impact information on CYP2B7P1

  • The amounts of each of the three mRNAs varied considerably between patients, but analysis of frequency distribution of the levels of CYP2B7 and CYP4B1 mRNAs did not present evidence for genetic polymorphism as a possible source of the observed interindividual variability [3].
  • Overall, the present study establishes that liver microsomal CYP2B and CYP3A preferentially catalyze cyclophosphamide and ifosphamide 4-hydroxylation, respectively, suggesting that liver P-450-inducing agents targeted at these enzymes might be used in cancer patients to enhance drug activation and therapeutic efficacy [4].
  • METHODS: We used multiplex PCR to amplify relevant gene fragments while avoiding amplification of the CYP2B7P1 pseudogene [5].
  • A specific direct sequencing strategy was developed based on CYP2B6 and CYP2B7 genomic sequence information and DNA from 35 subjects was completely analysed for mutations throughout all nine exons and their exon-intron boundaries [6].
  • CYP2B mRNA was detected in human liver, kidney, lung, trachea and intestine [7].
 

Biological context of CYP2B7P1

  • These results indicate that CYP2A7P2 is located near CYP2B7 in the middle of the CYP2A-2B-2F gene cluster on chromosome 19 [1].
  • 3. The current work utilizes the recently published substrate-bound CYP102 crystal structure as a template for construction of the CYP2B subfamily isoforms and shows, in particular, that known CYP2B6 substrate specificity and regioselectivity can be rationalized by putative active site interactions [8].
  • Although the linear relationships between lipophilicity and CYP2B-related activity point to a major role for desolvation of the enzyme binding site in the overall interaction, it is noted that there may be an optimal log P value displayed by preferred substrates as shown by parabolic relationships with this lipophilic parameter [9].
  • Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: the importance of lipophilicity for binding and metabolism [9].
 

Anatomical context of CYP2B7P1

  • Effects of administration of the chemoprotective agent oltipraz on CYP1A and CYP2B in rat liver and rat hepatocytes in culture [10].
  • Relative to controls, hepatic microsomes from dogs dosed with PCBs had higher levels of CYP1A1 detected in immunoblots and higher levels of EROD activity, but low levels of induction for CYP2B and PROD activity [11].
  • In these membranes the formation of DMBA-5,6-diol can be entirely accounted by the combined activity of members of the CYP2C and CYP2B families [12].
 

Associations of CYP2B7P1 with chemical compounds

  • Furthermore, liver samples of bortezomib-treated rats had little change in CYP2B and CYP4A protein levels and activities [13].
  • Results show that Propiverine induced several monooxygenases and CYP2B expression dose dependently [14].
  • No change in CYP2B or P450 reductase expression was observed, indicating that dimethyl sulfoxide effects were selective [15].
  • In contrast, orphenadrine, an inhibitor of CYP2B forms, produced a 51 +/- 4% decrease in S-mephenytoin N-demethylase activity in human liver microsomes and a 45% decrease in recombinant microsomes expressing CYP2B6 [16].
  • Lindane shares the criteria of the second and third groups and seems to induce both CYP1A and CYP2B activities [17].
 

Analytical, diagnostic and therapeutic context of CYP2B7P1

  • In general these results are in agreement with currently available evidence from substrate metabolism, mode of inhibitor action and site-directed mutagenesis experiments within the CYP2B subfamily of enzymes [18].
  • CYP2B expression was measured by Western blotting [14].

References

  1. Identification of a new human CYP2A gene fragment with close linkage to CYP2GP1. Sheng, J., Hua, Z., Guo, J., Caggana, M., Ding, X. Drug Metab. Dispos. (2001) [Pubmed]
  2. Low frequency of CYP2B deletions in Brazilian patients with congenital adrenal hyperplasia due to 21-hydroxylas deficiency. Bachega, T.A., Billerbeck, A.E., Madureira, G., Arnhold, I.J., Medeiros, M.A., Marcondes, J.A., Longui, C.A., Nicolau, W., Bloise, W., Mendonca, B.B. Hum. Hered. (1999) [Pubmed]
  3. Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal human lung and lung tumors. Czerwinski, M., McLemore, T.L., Gelboin, H.V., Gonzalez, F.J. Cancer Res. (1994) [Pubmed]
  4. Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Chang, T.K., Weber, G.F., Crespi, C.L., Waxman, D.J. Cancer Res. (1993) [Pubmed]
  5. MALDI-TOF Mass Spectrometry for Multiplex Genotyping of CYP2B6 Single-Nucleotide Polymorphisms. Blievernicht, J.K., Schaeffeler, E., Klein, K., Eichelbaum, M., Schwab, M., Zanger, U.M. Clin. Chem. (2007) [Pubmed]
  6. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Lang, T., Klein, K., Fischer, J., Nüssler, A.K., Neuhaus, P., Hofmann, U., Eichelbaum, M., Schwab, M., Zanger, U.M. Pharmacogenetics (2001) [Pubmed]
  7. Human CYP2B6: expression, inducibility and catalytic activities. Gervot, L., Rochat, B., Gautier, J.C., Bohnenstengel, F., Kroemer, H., de Berardinis, V., Martin, H., Beaune, P., de Waziers, I. Pharmacogenetics (1999) [Pubmed]
  8. Molecular modelling of CYP2B6, the human CYP2B isoform, by homology with the substrate-bound CYP102 crystal structure: evaluation of CYP2B6 substrate characteristics, the cytochrome b5 binding site and comparisons with CYP2B1 and CYP2B4. Lewis, D.F., Lake, B.G., Dickins, M., Eddershaw, P.J., Tarbit, M.H., Goldfarb, P.S. Xenobiotica (1999) [Pubmed]
  9. Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: the importance of lipophilicity for binding and metabolism. Lewis, D.F., Lake, B.G., Ito, Y., Anzenbacher, P. Drug metabolism and drug interactions. (2006) [Pubmed]
  10. Effects of administration of the chemoprotective agent oltipraz on CYP1A and CYP2B in rat liver and rat hepatocytes in culture. Langouët, S., Mahéo, K., Berthou, F., Morel, F., Lagadic-Gossman, D., Glaise, D., Coles, B., Ketterer, B., Guillouzo, A. Carcinogenesis (1997) [Pubmed]
  11. Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls. Korytko, P.J., Casey, A.C., Bush, B., Quimby, F.W. Toxicol. Sci. (1999) [Pubmed]
  12. The contribution of specific cytochromes P-450 in the metabolism of 7,12-dimethylbenz[a]anthracene in rat and human liver microsomal membranes. Morrison, V.M., Burnett, A.K., Forrester, L.M., Wolf, C.R., Craft, J.A. Chem. Biol. Interact. (1991) [Pubmed]
  13. Investigation of drug-drug interaction potential of bortezomib in vivo in female Sprague-Dawley rats and in vitro in human liver microsomes. Lu, C., Gallegos, R., Li, P., Xia, C.Q., Pusalkar, S., Uttamsingh, V., Nix, D., Miwa, G.T., Gan, L.S. Drug Metab. Dispos. (2006) [Pubmed]
  14. Influence of propiverine on hepatic microsomal cytochrome p450 enzymes in male rats. Walter, R., Ullmann, C., Thummler, D., Siegmund, W. Drug Metab. Dispos. (2003) [Pubmed]
  15. Posttranscriptional elevation of cytochrome P450 3A expression. Zangar, R.C., Hernandez, M., Novak, R.F. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  16. Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Heyn, H., White, R.B., Stevens, J.C. Drug Metab. Dispos. (1996) [Pubmed]
  17. Hierarchical cluster analysis of environmental pollutants through P450 induction in cultured hepatic cells. Dubois, M., Plaisance, H., Thomé, J.P., Kremers, P. Ecotoxicol. Environ. Saf. (1996) [Pubmed]
  18. Molecular modelling of CYP2B6 based on homology with the CYP2C5 crystal structure: analysis of enzyme-substrate interactions. Lewis, D.F., Lake, B.G., Dickins, M., Goldfarb, P.S. Drug metabolism and drug interactions. (2002) [Pubmed]
 
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