The functional effects of physical interactions involving cytochromes P450: putative mechanisms of action and the extent of these effects in biological membranes

References

• Alston K, Robinson RC, Park SS, et al. (1991). Interactions among cytochromes P-450 in the endoplasmic reticulum. Detection of chemically cross-linked complexes with monoclonal antibodies. J Biol Chem 266:735–739.
   PubMed Web of Science ®Google Scholar
• Anandatheerthavarada HK, Addya S, Dwivedi RS, et al. (1997). Localization of multiple forms of inducible cytochromes P450 in rat liver mitochondria: Immunological characteristics and patterns of xenobiotic substrate metabolism. Arch Biochem Biophys 339:136–150.
   PubMed Web of Science ®Google Scholar
• Atkins WM, Wang RW, Lu AY. (2001). Allosteric behavior in cytochrome p450-dependent in vitro drug-drug interactions: A prospective based on conformational dynamics. Chem Res Toxicol 14:338–347.
   PubMed Web of Science ®Google Scholar
• Baas BJ, Denisov IG, Sligar SG. (2004). Homotropic cooperativity of monomeric cytochrome P450 3A4 in a nanoscale native bilayer environment. Arch Biochem Biophys 430:218–228.
   PubMed Web of Science ®Google Scholar
• Backes WL, Batie CJ, Cawley GF. (1998). Interactions among P450 enzymes when combined in reconstituted systems: Formation of a 2B4-1A2 complex with a high affinity for NADPH-cytochrome P450 reductase. Biochemistry 37:12852–12859.
   PubMed Web of Science ®Google Scholar
• Causey KM, Eyer CS, Backes WL. (1990). Dual role of phospholipid in the reconstitution of cytochrome P-450 LM2-dependent activities. Mol Pharmacol 38:134–142.
   PubMed Web of Science ®Google Scholar
• Cawley GF, Batie CJ, Backes WL. (1995). Substrate-dependent competition of different P450 isozymes for limiting NADPH-cytochrome P450 reductase. Biochemistry 34:1244–1247.
   PubMed Web of Science ®Google Scholar
• Cawley GF, Zhang S, Kelley RW, Backes WL. (2001). Evidence supporting the interaction of CYP2B4 and CYP1A2 in microsomal preparations. Drug Metab Dispos 29:1529–1534.
   PubMed Web of Science ®Google Scholar
• Davydov DR. (2011). Microsomal monooxygenase as a multienzyme system: The role of P450-P450 interactions. Expert Opin Drug Metab Toxicol 7:543–558.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Davydova NY, Sineva EV, et al. (2013). Pivotal role of P450-P450 interactions in CYP3A4 allostery: The case of alpha-naphthoflavone. Biochem J 453:219–230.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Davydova NY, Sineva EV, Halpert JR. (2015). Interactions among cytochromes P450 in microsomal membranes: Oligomerization of cytochromes P450 2E1, 3A5, and 2E1 and its functional consequences. J Biol Chem 290:3850–3864.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Deprez E, Hoa GH, et al. (1995). High-pressure-induced transitions in microsomal cytochrome P450 2B4 in solution: Evidence for conformational inhomogeneity in the oligomers. Arch Biochem Biophys 320:330–344.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Fernando H, Baas BJ, et al. (2005). Kinetics of dithionite-dependent reduction of cytochrome P450 3A4: Heterogeneity of the enzyme caused by its oligomerization. Biochemistry 44:13902–13913.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Halpert JR. (2008). Allosteric P450 mechanisms: Multiple binding sites, multiple conformers or both? Expert Opin Drug Metab Toxicol 4:1523–1535.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Karyakin AV, Binas B, et al. (1985). Kinetic studies on reduction of cytochromes P-450 and b5 by dithionite. Eur J Biochem 150:155–159.
   PubMedGoogle Scholar
• Davydov DR, Kariakin AA, Petushkova NA, Peterson JA. (2000a). Association of cytochromes P450 with their reductases: Opposite sign of the electrostatic interactions in P450BM-3 as compared with the microsomal 2B4 system. Biochemistry 39:6489–6497.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Knyushko TV, Hoa GH. (1992). High pressure induced inactivation of ferrous cytochrome P-450 LM2 (IIB4) CO complex: Evidence for the presence of two conformers in the oligomer. Biochem Biophys Res Commun 188:216–221.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Petushkova NA, Archakov AI, Hoa GH. (2000b). Stabilization of P450 2B4 by its association with P450 1A2 revealed by high-pressure spectroscopy. Biochem Biophys Res Commun 276:1005–1012.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Petushkova NA, Bobrovnikova EV, et al. (2001). Association of cytochromes P450 1A2 and 2B4: Are the interactions between different P450 species involved in the control of the monooxygenase activity and coupling? Adv Exp Med Biol 500:335–338.
   PubMed Web of Science ®Google Scholar
• Davydov DR, Sineva EV, Sistla S, et al. (2010). Electron transfer in the complex of membrane-bound human cytochrome P450 3A4 with the flavin domain of P450BM-3: The effect of oligomerization of the heme protein and intermittent modulation of the spin equilibrium. Biochim Biophys Acta 1797:378–390.
   PubMed Web of Science ®Google Scholar
• Denisov IG, Sligar SG. (2012). A novel type of allosteric regulation: Functional cooperativity in monomeric proteins. Arch Biochem Biophys 519:91–102.
   PubMed Web of Science ®Google Scholar
• Depierre JW, Dallner G. (1975). Structural aspects of the membrane of the endoplasmic reticulum. Biochim Biophys Acta 415:411–472.
   PubMed Web of Science ®Google Scholar
• Dong MS, Bell LC, Guo Z, et al. (1996a). Identification of retained N-formylmethionine in bacterial recombinant mammalian cytochrome P450 proteins with the N-terminal sequence MALLLAVFL…: Roles of residues 3-5 in retention and membrane topology. Biochemistry 35:10031–10040.
   PubMed Web of Science ®Google Scholar
• Dong H, Shertzer HG, Genter MB, et al. (2013). Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins. Biochem Biophys Res Commun 435:727–732.
   PubMed Web of Science ®Google Scholar
• Dong MS, Yamazaki H, Guo ZY, Guengerich FP. (1996b). Recombinant human cytochrome P450 1A2 and an N-terminal- truncated form: Construction, purification, aggregation properties, and interactions with flavodoxin, ferredoxin, and NADPH-cytochrome P450 reductase. Arch Biochem Biophys 327:11–19.
   PubMed Web of Science ®Google Scholar
• Fernando H, Halpert JR, Davydov DR (2000). Kinetics of electron transfer in the complex of cytochrome P450 3A4 with the flavin domain of cytochrome P450BM-3 as evidence of functional heterogeneity of the heme protein. Arch Biochem Biophys 471:20–31.
   Web of Science ®Google Scholar
• Genter MB, Clay CD, Dalton TP, et al. (2006). Comparison of mouse hepatic mitochondrial versus microsomal cytochromes P450 following TCDD treatment. Biochem Biophys Res Commun 342:1375–1381.
   PubMed Web of Science ®Google Scholar
• Gomes AM, Winter S, Klein K, et al. (2009). Pharmacogenomics of human liver cytochrome P450 oxidoreductase: Multifactorial analysis and impact on microsomal drug oxidation. Pharmacogenomics 10:579–599.
   PubMed Web of Science ®Google Scholar
• Gorsky LD, Koop DR, Coon MJ. (1984). On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem 259:6812–6817.
   PubMed Web of Science ®Google Scholar
• Gruenke LD, Konopka K, Cadieu M, Waskell L. (1995). The stoichiometry of the cytochrome P-450-catalyzed metabolism of methoxyflurane and benzphetamine in the presence and absence of cytochrome b(5). J Biol Chem 270:24707. available from: http://www.jbc.org/cgi/content/abstract/270/42/24707
   PubMed Web of Science ®Google Scholar
• Guengerich FP. (2006). A malleable catalyst dominates the metabolism of drugs. Proc Natl Acad Sci U S A 103:13565–13566.
   PubMed Web of Science ®Google Scholar
• Guengerich FP, Krauser JA, Johnson WW. (2004). Rate-limiting steps in oxidations catalyzed by rabbit cytochrome P450 1A2. Biochemistry 43:10775–10788.
   PubMed Web of Science ®Google Scholar
• Guengerich FP, Ueng YF, Kim BR, et al. (1996). Activation of toxic chemicals by cytochrome p450 enzymes - Regio- and stereoselective oxidation of aflatoxin B1. Adv Exp Med Biol 387:7–15.
   PubMedGoogle Scholar
• Gut J, Richter C, Cherry RJ, et al. (1982). Rotation of cytochrome P-450. II. Specific interactions of cytochrome P-450 with NADPH-cytochrome P-450 reductase in phospholipid vesicles. J Biol Chem 257:7030–7036.
   PubMed Web of Science ®Google Scholar
• Hazai E, Kupfer D. (2005). Interactions between CYP2C9 and CYP2C19 in reconstituted binary systems influence their catalytic activity: Possible rationale for the inability of CYP2C19 to catalyze methoxychlor demethylation in human liver microsomes. Drug Metab Dispos 33:157–164.
   PubMed Web of Science ®Google Scholar
• Henderson CJ, McLaughlin LA, Wolf CR. (2013). Evidence that cytochrome b5 and cytochrome b5 reductase can act as sole electron donors to the hepatic cytochrome P450 system. Mol Pharmacol 83:1209–1217.
   PubMed Web of Science ®Google Scholar
• Hildebrandt A, Estabrook RW. (1971). Evidence for the participation of cytochrome b 5 in hepatic microsomal mixed-function oxidation reactions. Arch Biochem Biophys 143:66–79.
   PubMed Web of Science ®Google Scholar
• Houston JB, Galetin A. (2005). Modeling atypical CYP3A4 kinetics: Principles and pragmatism. Arch Biochem Biophys 433:351–360.
   PubMed Web of Science ®Google Scholar
• Houston JB, Kenworthy KE. (2000). In vitro-in vivo scaling of CYP kinetic data not consistent with the classical Michaelis–Menten model. Drug Metab Dispos 28:246–254.
   PubMed Web of Science ®Google Scholar
• Hu Y, Krausz K, Gelboin HV, Kupfer D. (2004). CYP2C subfamily, primarily CYP2C9, catalyzes the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: Use of inhibitory monoclonal antibodies in P450 identification. Xenobiotica 34:117–132.
   PubMed Web of Science ®Google Scholar
• Hu Y, Kupfer D. (2002). Metabolism of the endocrine disruptor pesticide-methoxychlor by human P450s: Pathways involving a novel catechol metabolite. Drug Metab Dispos 30:1035–1042.
   PubMed Web of Science ®Google Scholar
• Jamakhandi AP, Kuzmic P, Sanders DE, Miller GP. (2007). Global analysis of protein-protein interactions reveals multiple CYP2E1-reductase complexes. Biochemistry 46:10192–10201.
   PubMed Web of Science ®Google Scholar
• Jansson I, Schenkman JB. (1987). Influence of cytochrome b5 on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P-450. Drug Metab Dispos 15:344–348.
   PubMed Web of Science ®Google Scholar
• Kaminsky LS, Guengerich FP. (1985). Cytochrome P-450 isozyme/isozyme functional interactions and NADPH-cytochrome P-450 reductase concentrations as factors in microsomal metabolism of warfarin. Eur J Biochem 149:479–489.
   PubMedGoogle Scholar
• Kaminsky LS, Guengerich FP, Dannan GA, Aust SD. (1983). Comparisons of warfarin metabolism by liver microsomes of rats treated with a series of polybrominated biphenyl congeners and by the component-purified cytochrome P-450 isozymes. Arch Biochem Biophys 225:398–404.
   PubMed Web of Science ®Google Scholar
• Kandel SE, Lampe JN. (2014). Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity. Chem Res Toxicol 27:1474–1486.
   PubMed Web of Science ®Google Scholar
• Kelley RW, Cheng D, Backes WL. (2006). Heteromeric complex formation between CYP2E1 and CYP1A2: Evidence for the involvement of electrostatic interactions. Biochemistry 45:15807–15816.
   PubMed Web of Science ®Google Scholar
• Kenaan C, Shea EV, Lin HL, et al. (2013). Interactions between CYP2E1 and CYP2B4: Effects on affinity for NADPH-cytochrome P450 reductase and substrate metabolism. Drug Metab Dispos 41:101–110.
   PubMed Web of Science ®Google Scholar
• Korzekwa KR, Krishnamachary N, Shou M, et al. (1998). Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 37:4137–4147.
   PubMed Web of Science ®Google Scholar
• Laursen T, Jensen K, Moller BL. (2011). Conformational changes of the NADPH-dependent cytochrome P450 reductase in the course of electron transfer to cytochromes P450. Biochim Biophys Acta 1814:132–138.
   PubMed Web of Science ®Google Scholar
• Li B, Yau P, Kemper B. (2011). Identification of cytochrome P450 2C2 protein complexes in mouse liver. Proteomics 11:3359–3368.
   PubMed Web of Science ®Google Scholar
• Li DN, Pritchard MP, Hanlon SP, Burchell B, Wolf CR, Friedberg T (2000). Competition between cytochrome P-450 isozymes for NADPH-cytochrome P-450 oxidoreductase affects drug metabolism J Pharmacol Exp Ther 289:661–667.
   Web of Science ®Google Scholar
• Lin HL, Myshkin E, Waskell L, Hollenberg PF. (2007). Peroxynitrite inactivation of human cytochrome P450s 2B6 and 2E1: Heme modification and site-specific nitrotyrosine formation. Chem Res Toxicol 20:1612–1622.
   PubMed Web of Science ®Google Scholar
• Loida PJ, Sligar SG. (1993). Molecular recognition in cytochrome P-450: Mechanism for the control of uncoupling reactions. Biochemistry 32:11530–11538.
   PubMed Web of Science ®Google Scholar
• Lynch T, Price A. (2007). The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 76:391–396.
   PubMed Web of Science ®Google Scholar
• Ozalp C, Szczesna-Skorupa E, Kemper B. (2005). Bimolecular fluorescence complementation analysis of cytochrome p450 2c2, 2e1, and NADPH-cytochrome p450 reductase molecular interactions in living cells. Drug Metab Dispos 33:1382–1390.
   PubMed Web of Science ®Google Scholar
• Peterson JA, Ebel RE, O'keeffe DH, et al. (1976). Temperature dependence of cytochrome P-450 reduction. A model for NADPH-cytochrome P-450 reductase: Cytochrome P-450 interaction. J Biol Chem 251:4010–4016.
   PubMed Web of Science ®Google Scholar
• Ramsden D, Tweedie DJ, Chan TS, Tracy TS. (2014). Altered CYP2C9 activity following modulation of CYP3A4 levels in human hepatocytes: An example of protein-protein interactions. Drug Metab Dispos 42:1940–1946.
   PubMedGoogle Scholar
• Reed JR, Backes WL. (2012). Formation of P450.P450 complexes and their effect on P450 function. Pharmacol Ther 133:299–310.
   PubMed Web of Science ®Google Scholar
• Reed JR, Brignac-Huber LM, Backes WL. (2008). Physical incorporation of NADPH-cytochrome P450 reductase and cytochrome P450 into phospholipid vesicles using glycocholate and bio-beads. Drug Metab Dispos 36:582–588.
   PubMed Web of Science ®Google Scholar
• Reed JR, Cawley GF, Ardoin TG, et al. (2014). Environmentally persistent free radicals inhibit cytochrome P450 activity in rat liver microsomes. Toxicol Appl Pharmacol 277:200–209.
   PubMed Web of Science ®Google Scholar
• Reed JR, Cawley GF, Backes WL. (2011). Inhibition of cytochrome P450 1A2-mediated metabolism and production of reactive oxygen species by heme oxygenase-1 in rat liver microsomes. Drug Metab Lett 5:6–16.
   PubMedGoogle Scholar
• Reed JR, Cawley GF, Backes WL. (2013). Interactions between cytochromes P450 2B4 (CYP2B4) and 1A2 (CYP1A2) lead to alterations in toluene disposition and P450 uncoupling. Biochemistry 52:4003–4013.
   PubMed Web of Science ®Google Scholar
• Reed JR, Connick JP, Cheng D, et al. (2012). Effect of homomeric P450-P450 complexes on P450 function . Biochem J 446:489–497.
   PubMed Web of Science ®Google Scholar
• Reed JR, Cruz AL, Lomnicki SM, Backes WL. (2015a). Inhibition of cytochrome P450 2B4 by environmentally persistent free radical-containing particulate matter. Biochem Pharmacol 95:126–132.
   PubMed Web of Science ®Google Scholar
• Reed JR, Dela Cruz AL, Lomnicki SM, Backes WL. (2015b). Environmentally persistent free radical-containing particulate matter competitively inhibits metabolism by cytochrome P450 1A2. Toxicol Appl Pharmacol 289:223–230.
   PubMed Web of Science ®Google Scholar
• Reed JR, Eyer M, Backes WL. (2010). Functional interactions between cytochromes P450 1A2 and 2B4 require both enzymes to reside in the same phospholipid vesicle: Evidence for physical complex formation. J Biol Chem 285:8942–8952.
   PubMed Web of Science ®Google Scholar
• Reed JR, Hollenberg PF. (2003). Examining the mechanism of stimulation of cytochrome P450 by cytochrome b5: The effect of cytochrome b5 on the interaction between cytochrome P450 2B4 and P450 reductase. J Inorg Biochem 97:265–275.
   PubMed Web of Science ®Google Scholar
• Reed JR, Kelley RW, Backes WL. (2006). An evaluation of methods for the reconstitution of cytochromes P450 and NADPH P450 reductase into lipid vesicles. Drug Metab Dispos 34:660–666.
   PubMed Web of Science ®Google Scholar
• Robin MA, Maratrat M, Le Roy M, et al. (1996). Antigenic targets in tienilic acid hepatitis - Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera. J Clin Invest 98:1471–1480.
   PubMed Web of Science ®Google Scholar
• Sevrioukova I, Truan G, Peterson JA. (1996). The flavoprotein domain of P450BM-3: Expression, purification, and properties of the flavin adenine dinucleotide- and flavin mononucleotide-binding subdomains. Biochemistry 35:7528–7535.
   PubMed Web of Science ®Google Scholar
• Stringer RA, Strain-Damerell C, Nicklin P, Houston JB. (2009). Evaluation of recombinant cytochrome P450 enzymes as an in vitro system for metabolic clearance predictions. Drug Metab Dispos 37:1025–1034.
   PubMed Web of Science ®Google Scholar
• Subramanian M, Low M, Locuson CW, Tracy TS. (2009). CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis. Drug Metab Dispos 37:1682–1689.
   PubMed Web of Science ®Google Scholar
• Subramanian M, Zhang H, Tracy TS. (2010). CYP2C9-CYP3A4 protein-protein interactions: Role of the hydrophobic N terminus. Drug Metab Dispos 38:1003–1009.
   PubMed Web of Science ®Google Scholar
• Szczesna-Skorupa E, Chen CD, Rogers S, Kemper B. (1998). Mobility of cytochrome P450 in the endoplasmic reticulum membrane. Proc Natl Acad Sci U S A 95:14793–14798.
   PubMed Web of Science ®Google Scholar
• Szczesna-Skorupa E, Mallah B, Kemper B. (2003). Fluorescence resonance energy transfer analysis of cytochromes P450 2C2 and 2E1 molecular interactions in living cells. J Biol Chem 278:31269–31276.
   PubMed Web of Science ®Google Scholar
• Tan YZ, Patten CJ, Smith P, Yang CS (2000). Competitive interactions between cytochromes P450 2A6 and 2E1 for NADPH-cytochrome P450 oxidoreductase in the microsomal membranes produced by a baculovirus expression system Arch Biochem Biophys 342:82–91.
   Web of Science ®Google Scholar
• Tsalkova TN, Davydova NY, Halpert JR, Davydov DR. (2007). Mechanism of interactions of alpha-naphthoflavone with cytochrome P450 3A4 explored with an engineered enzyme bearing a fluorescent probe. Biochemistry 46:106–119.
   PubMed Web of Science ®Google Scholar
• West SB, Lu AYH. (1972). Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds and endogenous substrates. V. Competition between cytochromes P-450 and P-448 for reductase in 3,4-benzpyrene hydroxylation. Arch Biochem Biophys 153:298–303.
   PubMed Web of Science ®Google Scholar
• White RE, Coon MJ. (1980). Oxygen activation by cytochrome P-450. Annu Rev Biochem 49:315–356.
   PubMed Web of Science ®Google Scholar
• Wibo M, Amar-Costesec A, Berthet J, Beaufay H. (1971). Electron microscope examination of subcellular fractions. 3. Quantitative analysis of the microsomal fraction isolated from rat liver. J Cell Biol 51:52–71.
   PubMed Web of Science ®Google Scholar
• Yamazaki H, Gillam EMJ, Dong MS, et al. (1997). Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with cytochrome P450 3A4 and other forms: Effects of cytochrome P450-P450 and cytochrome P450-b5 interactions. Arch Biochem Biophys 342:329–337.
   PubMed Web of Science ®Google Scholar
• Yamazaki H, Johnson WW, Ueng YF, et al. (1996a). Lack of electron transfer from cytochrome b5 in stimulation of catalytic activities of cytochrome P450 3A4 Characterization of a reconstituted cytochrome P450 3A4 NADPH-cytochrome P450 reductase system and studies with apo-cytochrome b5. J Biol Chem 271:27438–27444.
   PubMed Web of Science ®Google Scholar
• Yamazaki H, Nakano M, Gillam EMJ, et al. (1996b). Requirements for cytochrome b5 in the oxidation of 7- ethoxycoumarin, chlorzoxazone, aniline, and N-nitrosodimethylamine by recombinant cytochrome P450 2E1 and by human liver microsomes. Biochem Pharmacol 52:301–309.
   PubMed Web of Science ®Google Scholar
• Yun CH, Miller GP, Guengerich FP. (2000). Rate-determining steps in phenacetin oxidations by human cytochrome P450 1A2 and selected mutants. Biochemistry 39:11319–11329.
   PubMed Web of Science ®Google Scholar