• 검색어에 아래의 연산자를 사용하시면 더 정확한 검색결과를 얻을 수 있습니다.
  • 검색연산자
검색연산자 기능 검색시 예
() 우선순위가 가장 높은 연산자 예1) (나노 (기계 | machine))
공백 두 개의 검색어(식)을 모두 포함하고 있는 문서 검색 예1) (나노 기계)
예2) 나노 장영실
| 두 개의 검색어(식) 중 하나 이상 포함하고 있는 문서 검색 예1) (줄기세포 | 면역)
예2) 줄기세포 | 장영실
! NOT 이후에 있는 검색어가 포함된 문서는 제외 예1) (황금 !백금)
예2) !image
* 검색어의 *란에 0개 이상의 임의의 문자가 포함된 문서 검색 예) semi*
"" 따옴표 내의 구문과 완전히 일치하는 문서만 검색 예) "Transform and Quantization"
쳇봇 이모티콘
ScienceON 챗봇입니다.
궁금한 것은 저에게 물어봐주세요.

논문 상세정보


In order to assess the possibility whether CYP2D is involved in caffeine metabolism, we have purified and characterized the rat liver microsomal cytochrome P4502D1 (CYP2D1), equivalent to CYP2D6 in human liver, and have utilized the reconstituted CYP2D1 in the metabolism of 4 primary caffeine (1, 3, 7-trimethylxanthine) metabolites such as paraxanthine (1, 7-dimethylxanthine), 1, 3, 7-trimethylurate, theophylline (1, 3-dimethylxanthine) and theobromine (3, 7-dimethylxanthine). Rat liver CYP 2D1 has been purified to a specific content of 8.98 nmole/mg protein (13.4fold purification, 1.5% yield) using $\omega$-aminooctylagarose, hydroxlapatite, and DE52 columns in a sequential manner. As judged from sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), the purified CYP2D1 was apparently homogeneous. Molecular weight of the purified CYP2D1 was found to be 51, 000 Da. Catalytic activity of the purified and then reconstituted CYP2D1 was confirmed by using bufuralol, a known subsFate of CYP2D1. The reconstituted CYP2D1 was found to produce to 1-hydroxylbufuralol at a rate of 1.43$\pm$0.13 nmol/min/nmol P450. The kinetic analysis of bufuralol hydroxylation indicated that Km and Vmax values were 7.32$\mu M$ and 1.64 nmol/min/nmol P450, respectively. The reconstituted CYP2D1 could catalyze the 7-demethylation of PX to 1-methylxanthine at a rate of 12.5 pmol/min/pmol, and also the 7- and 3- demethylations of 1, 3, 7-trimethylurate to 1, 3-dimethylurate and 1, 7-dimethylurate at 6.5 and 12.8 pmol/min/pmol CYP2D1, respectively. The reconstituted CYP2D1 could also 3-demethylate theophylline to 1-methylxanthine at 5 pmol/min/pmol and hydroxylate the theophylline to 1, 3-dimethylurate at 21.8 pmol/min/pmol CYP2D1. The reconstituted CYP2D1, however, did not metabolize TB at all (detection limits were 0.03 pmol/min/pmol). This study indicated that CYP2D1 is involved in 3-and 7-demethylations of paraxanthine and theophylline and suggested that CYP2D6 (equivalent to CYP2D1 in rat liver) present in human liver may be involved in the secondary metabolism of the primary metabolites of caffeine.

참고문헌 (21)

  1. Differential roles of cytochromes P450 2D1, 2C11, and 1A1/2 in the hydroxylation of bufuralol by rat liver microsomes , Mimura M.;Yamazaki H.;Sugahara C.;Hiro T.;Funae Y.;Shimada T. , Biochem. Pharmacol. / v.47,pp.1957-1963, 1994
  2. Human cytochrome $P-450_{PA}$ (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines , Butler M.A.;Iwasaki M.;Guengerich P.F.;Kadlubar F.F. , Proc. Natl. Acad. Sci. / v.86,pp.7696-7700, 1989
  3. Use of caffeine metabolites ratios to explore CYP1A2 and xanthine oxidase activities , Kalow W.;Tang B. , Clin. Pharmaco. Ther. / v.50,pp.508-519, 1991
  4. The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trial names of enzymes and nomenclature , Nelson D.R.;Kamataki T.;Waxman D.J.;Guengerich P.F.;Estabrook R.W.;Feyereisen R.;Gonzalez F.J.;Coon M.J.;Gunsalus I.C.;Gotoh O.;Okuda K.;Nerbert D.W. , DNA Cell Biol. / v.12,pp.1-51, 1993
  5. Accelerated caffeine metabolism after omeprazole treatment is indicated by urinary metabolite ratios: Coincidence with plasma clearance and breath test , Rost K.L.;Roots I. , Clin. Pharmaco. Ther. / v.55,pp.402-411, 1994
  6. Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population , Agundez J.A.;Ledesma M.C.;Ladero J.M.;Benitez J. , Clin. Pharmaco. Ther. / v.57,pp.265-269, 1995
  7. Determination of CYP1A2 and NAT2 phenotype in human populations by analysis of caffeine urinary metabolites , Butler M.A.;Lang N.P.;Young J.F.;Caporaso N.E.;Vineis P.;Hayes R.B.;Teitel C.H.;Massengill J.P.;Lawsen M.F.;Kadlubar F.F. , Pharmacogenetics / v.2,pp.116-127, 1992
  8. Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: Absence of mutation prescribing the phenotype in the CYP1A2 gene , Nakajima M.;Yokoi T.;Mizutani M.;Shin S.;Kadlubar F.F.;Kamataki T. , Cancer Epidemiol. Biomarkers Prev. / v.3,pp.413-421, 1994
  9. Protein measurement with folin phenol reagent , Lowry O.H.;Rosebrough N.J.;Farr A.L.;Randall R.J. , J. Biol. Chem. / v.193,pp.256-275, 1951
  10. Debrisoquine/sparteine-type polymorphism of drug oxidation , Gut J.;Catin T.;Dayer P.;Kronbach T.;Zanger U.;Meyer U.A. , J. Biol. Chem. / v.261,pp.11734-11743, 1986
  11. Pronounced differences between native Chinese and Swedish population in the polymorphic hydroxylations of debrisoquine and S-mephenytoin , Bertilsson L.;Lou Y-Q.;Du Y-L.;Kuang T-Y.;Liao X-M.;Wang K-Y.;Reviriego J.;Iselius L.;Sjoqvist F. , Clin. Pharmaco. Ther. / v.51,pp.388-397, 1992
  12. Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms , Fuhr U.;Doehmer J.;Battula N.;Wolfel C.;Kudla C.;Keita Y.;Staib A.H. , Biochem. Pharmacol. / v.43,pp.225-235, 1992
  13. Polymorphic hydroxylation of debrisoquine in man , Mahgoub A.;Idle J.R.;Dring L.G.;Lancaster R.;Smith R.L. , Lancet / v.2,pp.584-586, 1977
  14. The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature , Omura R.;Sato T. , J. Biol. Chem. / v.239,pp.2370-2378, 1964
  15. Caffeine urinary metabolite ratios as markers of enzyme activity: A theoretical assessment , Rostami-Hodjegan A.;Nurminen S.;Jackson P.R.;Tucker G.T. , Pharmacogenetics / v.6,pp.121-149, 1997
  16. Differential inhibition of flavin-containing monooxygenase with grapefruit juice , Chung W.G.;Kang J.H.;Roh H.K.;Cha Y.N. , The Toxicologist / v.36,pp.1789, 1997
  17. The CYP2D gene subfamily: Analysis of the molecular basis of the debrisoquine 4-hydroxylase deficiency in DA rats , Matsunaga E.;Zanger U.M.;Hardwick J.P.;Gelboin H.V.;Meyer U.A.;Gonzalez F.J. , Biochem. / v.28,pp.7349-7355, 1989
  18. Pharmacogentic phenotyping and genotyping , Gonzalez F.J.;Idle J.R. , Clin. Pharmacokinet. / v.26,pp.59-70, 1994
  19. Characterization of human cytochrome P450 involved in theophylline 8-hydroxylation , Zhang Z. Y.;Kaminsky L.S. , Biochem. Pharmacol. / v.50,pp.205-211, 1995
  20. Caffeine metabolism by human hepatic cytochrome P450: Contributions of 1A2, 2E1 and 3A isoforms , Tassaneeyakul W.;Birkett D.J.;McManus M.E.;Tassaneeyakul W.;Veronese M.E.;Andersson T.;Tukey R.T.;Miners J.O. , Biochem. Pharmacol. / v.47,pp.1767-1776, 1994
  21. Evidence for the involvement of several cytochrome P-450 in the first steps of caffeine metabolism by human liver microsomes , Berthou F.;Flinois J.;Ratanasavanh D.;Beaune P.;Riche C.;Guillouzo A. , Drug Metab. Dispos. / v.19,pp.561-567, 1991

이 논문을 인용한 문헌 (0)

  1. 이 논문을 인용한 문헌 없음


원문 PDF 다운로드

  • ScienceON :

원문 URL 링크

원문 PDF 파일 및 링크정보가 존재하지 않을 경우 KISTI DDS 시스템에서 제공하는 원문복사서비스를 사용할 수 있습니다. (원문복사서비스 안내 바로 가기)

상세조회 0건 원문조회 0건

DOI 인용 스타일