Abstract
Methyl tert-butyl ether (MTBE) is widely used as gasoline oxygenate and octane number enhancer for more complete combustion in order to reduce the air pollution caused by motor vehicle exhaust. The possible adverse effects of MTBE on human health are of major public concern. However, information on the metabolism of MTBE in human tissues is scarce. The present study demonstrates that human cytochrome P450 2A6 is able to metabolize MTBE to tert-butyl alcohol (TBA), a major circulating metabolite and marker for exposure to MTBE. As CYP2A6 is known to be constitutively expressed in human livers, we infer that it may play a significant role in metabolism of gasoline ethers in liver tissue.
Similar content being viewed by others
References
Brady JF, Xiao F, Ning SM, Yang CS (1990) Metabolism of methyl tertiary-butyl ether by rat hepatic microsomes. Arch Toxicol 64:157–160
Bruijn J, Berthault F, Vegro S, Pellegrini G, Allanou R, Scheer S (2005) tert-Butyl methyl ether, series: 3rd priority list, vol 19. Office for Official Publications of the European Communities, Luxembourg
Cain WS, Leaderer BP, Ginsberg GL, Andrews LS, Cometto-Muniz JE, Gent JF, Buck M, Berglund LG, Mohsenin V, Monahan E, Kjaergaard S (1996) Acute exposure to low-level methyl tertiary-butyl ether (MTBE): human reactions and pharmacokinetic response. Inhalation Toxicol 8:21–48
Clayton Environmental Consultants (1991) Gasoline vapor exposure assessment for the American Petroleum Institute (API). Clayton project number 31774.00 American Petroleum Institute, Washington, DC
Coon MJ, White RE (1980) In dioxygen binding and activation by metal centers. Wiley, New York, p 73
EFOA—European Fuel Oxygenates Association (2005) MTBE resource guide. Version n. 3, 2nd Revision. http://www.efoa.org
Fischer A, Müller M, Klasmeier J (2004) Determination of Henry’s law constant for methyl tert-butyl ether (MTBE) at groundwater temperatures. Chemosphere 54:689–694
Hansen BG, Munn SJ, Pakalin S, Musset C, Luotamo M, de Bruijn J, Berthaoult F, Vegro S, Pellegrini G, Allanou R, Scheer S (2002) European Union risk assessment report, ter-butyl methyl ether, vol 19, EUR 20417 EN. Office for Official Publications of the European Communities, Luxembourg
Hong JY, Wang YY, Bondoc FY, Yang ChS, Lee M, Hung WQ (1997a) Rat olfactory mucosa displays a high activity in metabolizing methyl tert-butyl ether and other gasoline ethers. Fundam Appl Toxicol 40:205–210
Hong JY, Yang ChS, Lee M, Wang YY, Huang W, Tan Y, Patten CJ, Bondoc FY (1997b) Role of cytochromes P450 in the metabolism of methyl tert-butyl ether in human livers. Arch Toxicol 71:266–269
Hong JY, Wang YY, Bondoc FY, Lee M, Yang CS, Hu WY, Pan J (1999a) Metabolism of methyl tert-butyl ether and other gasoline ethers by human liver microsomes and heterologously expressed human cytochromes P450: identification of CYP2A6 as a major catalyst. Toxicol Appl Pharmacol 160:43–48
Hong JY, Wang YY, Bondoc FY, Yang ChS, Gonzalez FJ, Pan Zh, Cokonis CD, Hu WY, Bao Z (1999b) Metabolism of methyl tert-butyl ether and other gasoline ethers in mouse liver microsomes lacking cytochrome P450 2E1. Toxicol Lett 105:83–88
Imaoka S, Yamada T, Hiroi T, Hayashi K, Sakaki T, Yabusaki Y, Funae Y (1996) Multiple forms of human P450 expressed in Saccharomyces cerevisiae, systematic characterization and comparison with those of the rat. Biochem Pharmacol 51:1041–1050
Jacobs J, Juertin J, Herron C (2001) MTBE: effects on soil and groundwater resources. Lewis Publishers, Boca Raton, FL
Johanson G, Nihlen A, Lof A (1995) Toxicokinetics and acute effects of MTBE and ETBE in male volunteers. Toxicol Lett 83:713–718
Le Gal A, Dre′ano Y, Gervasi PG, Berthou F (2001) Human cytochrome P450 2A6 is the major enzyme involved in the metabolism of three alkoxyethers used as oxyfuels. Toxicol Lett 124:47–58
McLain J, Lee J, Groves JT (2000) Biomimetic oxidations catalyzed by transition metal complexes. Imperial College Press, London, p 91
Montellano PRO (1995) Cytochrome P-450: structure, mechanism and biochemistry, 2nd edn. Plenum Press, New York, p 652
Oberdorster E, Rittschor D, McClellan-Green P (1998) Induction of cytochrome P-4503A by tributyltin in blue crabs, Callinectes sapidus. Aqua Toxicol 41:83–100
Prah JD, Goldstein GM, Devlin R, Otto D, Ashley D, House D, Cohen KL, Gerrity T (1994) Sensory, symptomatic, in ammatory, and ocular responses to and the metabolism of methyl tertiary butyl ether in a controlled human exposure experiment. Inhalation Toxicol 6:521–538
Raunio H, Husgafvel-Pursiainen K, Anttila S, Hietanen E, Hirvonen A, Pelkonen O (1995) Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility-review. Genetics 159:113–121
Shaffer KL, Uchrin CG (1997) Uptake of methyl tertiary butyl ether (MTBE) by groundwater solids. Bull Environ Contam Toxicol 59:744–749
Shilov AE, Shteinman AA (1999) Oxygen atom transfer into C–H bond in biological and model chemical systems. Mechanistic aspects. Acc Chem Res 32:763–771
Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414–423
Snyder MJ (2000) Cytochrome P450 enzymes in aquatic invertebrates: recent advances and future directions. Aqua Toxicol 48:529–547
Sono M, Roach MP, Coulter ED, Dawson JH (1996) Heme-containing oxygenases. Chem Rev 96:2841–2888
Traylor TG, Traylor PS, Valentine JS, Foote CS, Greenberg A, Liebman JE (1995) Active oxygen in biochemistry, blackie academic and professional. Chapman and Hall, London, p 84
US EPA (2000) 40 CFR Part 755. Methyl tertiary butyl ether (MTBE): advance notice of intent to initiate rulemaking under the toxic substances control act to eliminate or limit the use of MTBE as a fuel additive in gasoline. Federal register, vol 65, no 58, pp 16094–16109
US EPA (2004) Technologies for treating MTBE and other fuel oxygenates. EPA report 542-R-04-009. Office of Solid Waste and Emergency Response; Office of Superfund Remediation and Technology Innovation, Washington, DC
Yoshizawa K, Shiota Y, Yamabe T (1998) Abstraction of the hydrogen atom of methane by iron–oxo species: the concerted reaction path is energetically more favorable. Organometallics 17:2825–2831
Yun CH, Shimada T, Guengerich FP (1991) Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol 40:679–685
Zogorski JS, Morduchowitz A, Baehr AL, Bauman BJ, Conrad DL, Drew RT, Korte NE, Lapham WW, Pankow JF, Washington ER (1997) Fuel oxygenates and water quality. In: Interagency assessment of oxygenated fuels, National Science and Technology Council (NSTC). Committee on Environment and Natural Resources, Washington, DC
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Shamsipur, M., Miran Beigi, A.A., Teymouri, M. et al. Biotransformation of methyl tert-butyl ether by human cytochrome P450 2A6. Biodegradation 23, 311–318 (2012). https://doi.org/10.1007/s10532-011-9510-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10532-011-9510-0