Oxidation of caffeine by CYP1A2: Isotope effects and metabolic switching

Drug Metabolism and Disposition

Volumn 33, Issue 12, 2005, Pages 1837-1844

  Regal, Kelly A ^a,b   Kunze, Kent L ^a   Peter, Raimund M ^a,c   Nelson, Sidney D ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b AMGEN INC   (United States)

^c ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CAFFEINE; CYTOCHROME P450; CYTOCHROME P450 1A2; DEUTERIUM; HYDROGEN; ISOTOPE; PARAXANTHINE; THEOBROMINE; THEOPHYLLINE; WATER;

ARTICLE; CONTROLLED STUDY; DEMETHYLATION; HUMAN; HUMAN TISSUE; METABOLITE; OXIDATION; PRIORITY JOURNAL; SYNTHESIS;

CAFFEINE; CATALYSIS; CYTOCHROME P-450 CYP1A2; DEUTERIUM; HUMANS; OXIDATION-REDUCTION;

EID: 28144446062     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.105.006031     Document Type: Article

References (40)

1. Atkins WM and Sligar SG (1986) Metabolic switching in cytochrome P-450cam: deuterium isotope effects on regiospecificity and the monooxygenase/oxidase ratio. J Am Chem Soc 109:3754-3760.
2. Atkins WM and Sligar SG (1988) Deuterium isotope effects in norcamphor metabolism by cytochrome P-450cam: kinetic evidence for the two-electron reduction of a high-valent iron-oxo intermediate. Biochemistry 27:1610-1616.
3. Atkinson JK, Hollenberg PF, Ingold KU, Johnson CC, Le Tadic MH, Newcomb M, and Putt DA (1994) Cytochrome P450-catalyzed hydroxylation of hydrocarbons: kinetic deuterium isotope effects for the hydroxylation of an ultrafast radical clock. Biochemistry 33:10630-10637.
4. Bell RP (1974) Liversidge Lecture. Recent advances in the study of kinetic hydrogen isotope effects. Chem Soc Rev 3:513-544.
5. 3 theophylline. J Labelled Compd Radiopharm 24:275-289.
6. Constantino L, Rosa E, and Iley J (1992) The microsomal demethylation of N,N-dimethylbenzamides. Substituent and kinetic deuterium isotope effects. Biochem Pharmacol 44:651-658.
7. Darbyshire JF, Gillette JR, Nagata K, and Sugiyama K (1994) Deuterium isotope effects on A-ring and D-ring metabolism of testosterone by CYP2C11: evidence for dissociation of activated enzyme-substrate complexes. Biochemistry 33:2938-2944.
8. Ebner T, Meese CO, and Eichelbaum M (1995) Mechanism of cytochrome P450 2D6-catalyzed sparteine metabolism in humans. Mol Pharmacol 48:1078-1086.
9. Gillette JR, Darbyshire JF, and Sugiyama K (1994) Theory for the observed isotope effects on the formation of multiple products by different kinetic mechanisms of cytochrome P450 enzymes. Biochemistry 33:2927-2937.
10. Gu L, Gonzalez FJ, Kalow W, and Tang BK (1992) Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 2:73-77.
11. Haining RL, Hunter AP, Sadeque AJ, Philpot RM, and Rettie AE (1997) Baculovirus-mediated expression and purification of human FMO3: catalytic, immunochemical and structural characterization. Drug Metab Dispos 25:790-797.
12. Hall LR and Hanzlik RP (1990) Kinetic deuterium isotope effects on the N-demethylation of tertiary amides by cytochrome P-450. J Biol Chem 265:12349-12355.
13. Hall LR, Iwamoto RT, and Hanzlik RP (1989) Electrochemical models for cytochrome P-450. N-demethylation of tertiary amides by anodic oxidation. J Org Chem 54:2446-2451.
14. Harada N, Miwa GT, Walsh JS, and Lu AY (1984) Kinetic isotope effects on cytochrome P-450-catalyzed oxidation reactions. Evidence for the irreversible formation of an activated oxygen intermediate of cytochrome P-448. J Biol Chem 259:3005-3010.
15. Higgins L, Bennett GA, Shimoji M, and Jones JP (1998) Evaluation of cytochrome P450 mechanism and kinetics using kinetic deuterium isotope effects. Biochemistry 37:7039-7046.
16. Horning MG, Haegele KD, Sommer KR, Nowlin J, Stafford M, and Thenot JP (1976) Metabolic switching of drug pathways as a consequence of deuterium substitution, in Proceedings of the Second International Conference on Stable Isotopes (Klein ER and Klein PD eds), pp 41-54, CONF-751027, NTIS, Springfield, VA.
17. Iyer KR, Jones JP, Darbyshire JF, and Trager WF (1997) Intramolecular isotope effects for benzylic hydroxylation of isomeric xylenes and 4,4′-dimethylbiphenyl by cytochrome P450: relationship between distance of methyl groups and masking of the intrinsic isotope effect. Biochemistry 36:7136-7143.
18. Jones JP, Korzekwa KR, Rettie AE, and Trager WF (1986) Isotopically sensitive branching and its effect on the observed intramolecular isotope effects in cytochrome P-450 catalyzed reactions: a new method for the estimation of intrinsic isotope effects. J Am Chem Soc 108:7074-7078 [Correction (1988) J Am Chem Soc 7110:2018].
19. Jones JP, Rettie AE, and Trager WF (1990) Intrinsic isotope effects suggest that the reaction coordinate symmetry for the cytochrome P-450 catalyzed hydroxylation of octane is isozyme independent. J Med Chem 33:1242-1246.
20. Jones JP and Trager WF (1987) The separation of the intramolecular isotope effect for the cytochrome P-450 catalyzed hydroxylation of n-octane into its primary and secondary components. J Am Chem Soc 109:2171-2173 [Correction (1988) J Am Chem Soc 2110:2018].
21. Karki SB, Dinnocenzo JP, Jones JP, and Korzekwa KR (1995) Mechanism of oxidative amine dealkylation of substituted N,N-dimethylanilines by cytochrome P-450: application of isotope effect profiles. J Am Chem Soc 117:3657-3664.
22. Korzekwa KR, Trager WF, and Gillette JR (1989) Theory for the observed isotope effects from enzymatic systems that form multiple products via branched reaction pathways: cytochrome P-450. Biochemistry 28:9012-9018.
23. Lewis DF (1995) Three-dimensional models of human and other mammalian microsomal P450s constructed from an alignment with P450102 (P450bm3). Xenobiotica 25:333-366.
24. Lozano JJ, Lopez-de-Brinas E, Centeno NB, Guigo R, and Sanz F (1997) Three-dimensional modelling of human cytochrome P450 1A2 and its interaction with caffeine and MeIQ. J Comput-Aided Mol Des 11:395-408.
25. Miwa GT, Walsh JS, Kedderis GL, and Hollenberg PF (1983) The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions. J Biol Chem 258:14445-14449.
26. Miyata M, Nagata K, Yamazoe Y, and Kato R (1989) Isolation and characterization of human liver cytochrome b5 cDNA. Pharmacol Res 21:513-520.
27. Modi S, Gilham DE, Sutcliffe MJ, Lian LY, Primrose WU, Wolf CR, and Roberts GC (1997) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase. Biochemistry 36:4461-4470.
28. Modi S, Sutcliffe MJ, Primrose WU, Lian LY, and Roberts GC (1996) The catalytic mechanism of cytochrome P450 BM3 involves a 6 A movement of the bound substrate on reduction. Nat Struct Biol 3:414-417.
29. Nelson SD and Trager WF (2003) The use of deuterium isotope effects to probe the active site properties, mechanism of cytochrome P450-catalyzed reactions and mechanisms of metabolically dependent toxicity. Drug Metab Dispos 31:1481-1498.
30. Northrop D (1977) Determining the absolute magnitude of hydrogen isotope effects, in Isotope Effects on Enzyme-Catalyzed Reactions (Cleland WW, O'Leary MH, and Northrop DB eds), pp 122-152, University Park Press, Baltimore.
31. Omura T and Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification and properties. J Biol Chem 239:2379-2385.
32. Raucy JL and Lasker JM (1991) Isolation of P450 enzymes from human liver. Methods Enzymol 206:577-587.
33. Regal KA, Howald WN, Peter RM, Gartner CA, Kunze KL, and Nelson SD (1998) Subnanomolar quantification of caffeine's in vitro metabolites by stable isotope dilution gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 708:75-85.
34. Regal KA and Nelson SD (2000) Orientation of caffeine within the active site of human cytochrome P450 1A2 based on NMR longitudinal (T1) relaxation measurements. Arch Biochem Biophys 384:47-58.
35. Shea JP, Nelson SD, and Ford GP (1983) MNDO calculation of kinetic isotope effects in model cytochrome P-450 oxidations. J Am Chem Soc 105:5451-5454.
36. Shen AL, Porter TD, Wilson TE, and Kasper CB (1989) Structural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis. J Biol Chem 264:7584-7589.
37. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, and Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76-85.
38. Tassaneeyakul W, Birkett DJ, McManus ME, Veronese ME, Andersson T, Tukey RH, and Miners JO (1994) Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochem Pharmacol 47:1767-1776.
39. Yun CH, Miller GP, and Guengerich FP (2000) Rate-determining steps in phenacetin oxidations by human cytochrome P450 1A2 and selected mutants. Biochemistry 39:11319-11329.
40. Yun CH, Miller GP, and Guengerich FP (2001) Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis. Biochemistry 40:4521-4530.