Cytochrome P450 in Insects

  • R. Feyereisen
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


More than half the described species of eukaryotic organisms living on our planet are insects, and it is generally believed that a vast majority of insect species are still unknown. Among the known insect species are our best friends (pollinators of our crops) and our worst enemies (vectors of disease and avid consumers of our food). It is the chemical warfare against the latter that provided the framework for most of the early studies on insect cytochrome P450. The metabolism of insecticides, its inhibition by synergists such as piperonyl butoxide, and the resistance of insect pests to insecticides are only the most obvious reasons to study insect cytochrome P450. Insects are excellent model systems in which to study the induction of cytochrome P450 by dietary chemicals, or the molecular genetics of cytochrome P450. However, the study of cytochrome P450 has often been hampered by the small size of insects and the difficulty in obtaining enough tissue. Purification and reconstitution studies have been particularly difficulty (Hodgson 1985). Nonetheless, large numbers of insects obtained at low cost can sometimes compensate for small size, and the use of radiolabeled substrates has allowed enzymological studies of cytochrome P450 from tiny endocrine glands such as the corpora allata or the pro thoracic glands. This review is necessarily selective and will survey the known insect cytochromes P450 as well as some aspects of cytochrome P450 function in insects.


Juvenile Hormone Cytochrome P450 Enzyme Malpighian Tubule Musca Domestica Cytochrome P450 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agosin M (1982) Multiple forms of insect cytochrome P-450: role in insecticide resistance. In: Hietanen E (ed) Cytochrome P450; biochemistry, biophysics and environmental implications. Elsevier, Amsterdam, p 661Google Scholar
  2. Ahmad S, Kirkland KE, Blomquist GJ (1987) Evidence for a sex pheromone metabolizing cytochrome P-450 monooxygenase in the housefly. Arch Insect Biochem Physiol 6: 121–140CrossRefGoogle Scholar
  3. Asseffa A, Smith SJ, Nagata K, Gillette J, Gelboin HV, Gonzalez FJ (1989) Novel exogenous heme-dependent expression of mammalian cytochrome P450 using baculovirus. Arch Biochem Biophys 274: 481–490PubMedCrossRefGoogle Scholar
  4. Bigelow SW, Zijlstra JA, Vogel EW, Nebert DW (1985) Measurements of the cytosolic Ah receptor among four strains of Drosophila melanogaster. Arch Toxicol 56: 219–225PubMedCrossRefGoogle Scholar
  5. Blais C, Lafont R (1986) Ecdysone 20-hydroxylation in imaginal wing discs of Pieris brassicae (Lepidoptera): correlations with ecdysone and 20-hydroxyecdysone titers in pupae. Arch Insect Biochem Physiol 3: 501–512CrossRefGoogle Scholar
  6. Bradfield JY, Lee YH, Keeley LL (1991) Cytochrome P450 family 4 in a cockroach: molecular cloning and regulation by hypertrehalosemic hormone. Proc Natl Acad Sci USA 88: 4558–4562PubMedCrossRefGoogle Scholar
  7. Brattsten LB (1979) Ecological significance of mixed-function oxidations. Drug Metab Rev 10: 35–58PubMedCrossRefGoogle Scholar
  8. Brattsten LB (1987) Sublethal virus infection depresses cytochrome P-450 in an insect. Experientia 43: 451–454CrossRefGoogle Scholar
  9. Brattsten LB, Ahmad S (1986) Molecular aspects of insect-plant interactions. Plenum, New YorkGoogle Scholar
  10. Burger A, Roussel JP, Colobert F, Kappler C, Hetru C, Luu B, Hoffmann JA (1987) In vitro studies on potential selective and irreversible inhibitors of enzymes involved in the biosynthesis of ecdysone. Pestic Biochem Physiol 29: 197–208CrossRefGoogle Scholar
  11. Burger A, Roussel JP, Hetru C, Hoffman JA, Luu B (1989) Allenic cholesteryl derivatives as inhibitors of ecdysone biosynthesis. Tetrahedron 45: 155–164CrossRefGoogle Scholar
  12. Cariño F, Koener JF, Plapp FW Jr, Feyereisen R (1992) Expression of the cytochrome P450 gene CYP6A1 in the housefly, Musca domestica ACS Symp. Ser 505: 31–40Google Scholar
  13. Clarke SE, Brealey CJ, Gibson GG (1989) Cytochrome P-450 in the housefly: induction, substrate specificity and comparison to three rat hepatic isoenzymes. Xenobiotica 19: 1175–1180PubMedCrossRefGoogle Scholar
  14. Cohen MB, Schuler MA, Berenbaum MR (1992) A host-inducible cytochrome P450 from a host-specific caterpillar: molecular cloning and evolution. Proc Natl Acad Sci USA 89:(in press)Google Scholar
  15. Cuany A, Pralavorio M, Pauron D, Berge JB, Fournier D, Blais C, Lafont R, Salaun JP, Weissbart D, Larroque C, Lange R (1990) Characterization of microsomal oxidative activities in a wild-type and in a DDT resistant strain of Drosophila melanogaster. Pestic Biochem Physiol 37: 293–302CrossRefGoogle Scholar
  16. Dubendorfer A (1986) Ecdysone C20-hydroxylation and conjugate formation by Drosophila melanogaster cell lines. Arch Insect Biochem 16: 645–651Google Scholar
  17. Feyereisen R (1987) Chemical disruption of insect juvenile hormone biosynthesis. In: Greenhalgh R, Roberts TR (eds) Pesticide science and biotechnology. Blackwell, Oxford, p 113Google Scholar
  18. Feyereisen R, Durst F (1978) Ecdysterone biosynthesis; a microsomal cytochrome-P-450-linked ecdysone 20-monooxygenase from tissues of the African migratory locust. Eur J Biochem 88: 37–47PubMedCrossRefGoogle Scholar
  19. Feyereisen R, Durst F (1980) Development of microsomal cytochrome P-450 monooxygenases during the last larval instar of the locust, Locusta migratoria: correlation with the hemolymph 20-hydroxyecdysone titer. Mol Cell Endocrinol 20: 157–169PubMedCrossRefGoogle Scholar
  20. Feyereisen R, Vincent DR (1984) Characterization of antibodies to house fly NADPH-cytochrome P-450 reductase. Arch Insect Biochem 14: 163–168Google Scholar
  21. Feyereisen R, Pratt GE, Hamnett AF (1981) Enzymic synthesis of juvenile hormone in locust corpora allata: evidence for a microsomal cytochrome P-450 linked methyl farnesoate epoxidase. Eur J Biochem 118: 231–238PubMedCrossRefGoogle Scholar
  22. Feyereisen R, Koener JF, Farnsworth DE, Nebert DW (1989) Isolation and sequence of cDNA encoding a cytochrome P-450 from an insecticide-resistant strain of the house fly, Musca domestica. Proc Natl Acad Sci USA 86: 1465–1469PubMedCrossRefGoogle Scholar
  23. Ffrench-Constant RH, Roush RT (1991) Gene mapping and cross-resistance in cyclodiene insecticide-resistant Drosophila melanogaster ( Mg ). Genetics Research Cambridge 57: 17–21CrossRefGoogle Scholar
  24. Gandhi R, Varak E, Goldberg ML (1992) Molecular analysis of a cytochrome P450 gene of family 4 on the Drosophila X chromosome. DNA Cell Biol 11: 397–404PubMedCrossRefGoogle Scholar
  25. Greenwood DR, Rees HH (1984) Ecdysone 20-mono-oxygenase in the desert locust, Schistocerca gregaria. Biochem J 223: 837–847PubMedGoogle Scholar
  26. Halliday WR, Farnsworth DE, Feyereisen R (1986) Hemolymph ecdysteroid titer and midgut ecdysone 20-monooxygenase activity during the last larval stage of Diploptera punctata. Insect Biochem 16: 627–634CrossRefGoogle Scholar
  27. Hallstrom I (1985) Genetic regulation of the cytochrome P-450 system in Drosophila melanogaster: II. Localization of some genes regulating cytochrome P-450 activity. Chem Biol Interact 56: 173–184PubMedCrossRefGoogle Scholar
  28. Hammock BD (1975) NADPH dependent epoxidation of methyl farnesoate to juvenile hormone in the cockroach. Life Sci 17: 323–328PubMedCrossRefGoogle Scholar
  29. Hamnett AF, Pratt GE (1983) The absolute configuration of precocene I dihydrodiols produced by metabolism of precocene I by corpora allata of Locusta migratoria, in vitro. Life Sci 32: 2747–2753PubMedCrossRefGoogle Scholar
  30. Hodgson E (1985) Microsomal mono-oxygenases In: Kerkut GA, Gilbert LI (eds) Comprehensive insect physiology, biochemistry and pharmacology, vol 11. Pergamon, Oxford, pp 225–321Google Scholar
  31. Hoggard N, Rees HH (1988) Reversible activation-inactivation of mitochondrial ecdysone 20-mono-oxygenase: a possible role for phosphorylation- dephosphorylation. J Insect Physiol 34: 647–653CrossRefGoogle Scholar
  32. Hoggard N, Fisher MJ, Rees HH (1989) Possible role for covalent modification in the reversible activation of ecdysone 20-monooxygenase activity. Arch Insect Biochem Physiol 10:241–253CrossRefGoogle Scholar
  33. Houpt DR, Pursey JC, Morton RA (1988) Genes controlling malathion resistance in a laboratory-selected population of Drosophila melanogasterGoogle Scholar
  34. Hunt DWA, Smirle MJ (1988) Partial inhibition of pheromone production in Dendroctonus ponderosae ( Coleoptera: Scolytidae) by polysubstrate mono-oxygenase inhibitors. J Chem Ecol 14: 529–536CrossRefGoogle Scholar
  35. Jowett T, Wajidi MFF, Oxtoby E, Wolf CR (1991) Mammalian genes expressed in Drosophila: a transgenic model for the study of mechanisms of chemical mutagenesis and metabolism. EMBO J 10: 1075–1081PubMedGoogle Scholar
  36. Kalb VF, Loper JC (1988) Proteins from eight eukaryotic cytochrome P-450 families share a segmented region of sequence similarity. Proc Natl Acad Sci USA 85: 7221–7225PubMedCrossRefGoogle Scholar
  37. Kappler C, Kabbouh M, Durst F, Hoffman JA (1986) Studies on the C-2 hydroxylation of 2-deoxyecdysone in Locusta migratoria. Insect Biochem 16: 25–32CrossRefGoogle Scholar
  38. Kappler C, Kabbouh M, Hetru C, Durst F, Hoffman JA (1988) Characterization of three hydroxylases involved in the final steps of biosynthesis of the steroid hormone ecdysone in Locusta migratoria ( Insecta, Orthoptera). J Steroid Biochem 31: 891–898PubMedCrossRefGoogle Scholar
  39. Keogh DP, Johnson RF, Smith SL (1989) Regulation of cytochrome P-450 dependent steroid hydroxdylase activity in Manduca sexta: evidence for the involvement of a neuroendocrine-endocrine axis during larval-pupal development. Biochem Biophys Res Commun 165: 442–448PubMedCrossRefGoogle Scholar
  40. Koener JF, Cariño FA, Feyereisen R (1993) The cDNA and deduced protein sequence of house fly NADPH-cytochrome P450 reductase. Insect Biochem Mol Biol 23: (in press)Google Scholar
  41. Lehmann M, Koolman J (1986) The influence of forskolin on the metabolism of ecdysone and 20-hydroxyecdysone in isolated fat body of the blowfly, Calliphora vicina. Biol Chem Hoppe Seyler 367: 387–393PubMedCrossRefGoogle Scholar
  42. Mitchell MJ, Smith SL (1986) Characterization of ecdysone 20-monooxygenase activity in wandering stage larvae of Drosophila melanogaster. Insect Biochem 16: 525–537CrossRefGoogle Scholar
  43. Mitchell MJ, Smith SL (1988) Ecdysone 20-monooxygenase activity throughout the life cycle of Drosophila melanogaster. Gen Comp Endocrinol 72: 467–470PubMedCrossRefGoogle Scholar
  44. Ohta D, Matsuura Y, Sato R (1991) Expression and characterization of a rabbit liver cytochrome P450 with the aid of the baculovirus expression system. Biochem Biophys Res Commun 175: 394–399PubMedCrossRefGoogle Scholar
  45. Pratt GE, Kuwano E, Farnsworth DE, Feyereisen R (1990) Structure/activity studies on 1,5-disubstituted imidazoles as inhibitors of juvenile hormone biosynthesis in isolated corpora allata of the cockroach Diploptera punctata. Pestic Biochem Physiol 38: 223–230CrossRefGoogle Scholar
  46. Ronis MJJ, Hodgson E, Dauterman WC (1988) Characterization of multiple forms of cytochrome P-450 from an insecticide resistant strain of house fly ( Musca domestica ). Pestic Biochem Physiol 32: 74–90CrossRefGoogle Scholar
  47. Smith SL (1985) Regulation of ecdysteroid titer: synthesis. In: Kerkut GA, Gilbert LI (eds) Comprehensive insect physiology, biochemistry and pharmacology, vol 7. Pergamon, Oxford, p 295Google Scholar
  48. Smith SL, Bollenbacher WE, Cooper DY, Schleyer H, Wielgus JJ, Gilbert LI (1979) Ecdysone 20-monooxygenase: characterization of an insect cytochrome P-450 dependent steroid hydroxylase. Mol Cell Endocrinol 15: 111–133PubMedCrossRefGoogle Scholar
  49. Snyder M, Hirsh J, Davidson N (1981) The cuticle genes of Drosophila. A developmentally regulated gene cluster. Cell 25: 165–177PubMedCrossRefGoogle Scholar
  50. Srivatsan J, Kuwahara T, Agosin M (1987) The effect of alpha-ecdysone and phenobarbital on the alpha-ecdysone 20-monooxygenase of house fly larva. Biochem Biophys Res Commun 148: 1075–1080PubMedCrossRefGoogle Scholar
  51. Srivatsan J, Weirich M, Agosin M (1990) Cytochrome P-450-catalyzed formation of 20-hydroxy-ecdysone in larval housefly mitochondria. Biochem Biophys Res Commun 168: 1372–1377CrossRefGoogle Scholar
  52. Sundseth SS, Kennel SJ, Waters LC (1989) Monoclonal antibodies to resistance-related forms of cytochrome P450 in Drosophila melanogaster. Pestic Biochem Physiol 33: 176–188CrossRefGoogle Scholar
  53. Sundseth SS, Nix CE, Waters LC (1990) Isolation of insecticide resistance-related forms of cytochrome P-450 from Drosophila melanogaster. Biochem J 265: 213–217PubMedGoogle Scholar
  54. Waters LC, Nix CE (1988) Regulation of insecticide resistance-related cytochrome P-450 expression in Drosophila melanogaster. Pestic Biochem Physiol 30: 214–227CrossRefGoogle Scholar
  55. Waters LC, Ch’ang LY, Kennel SJ (1990) Studies on the expression of insecticide resistance-associated cytochrome P450 in Drosophila using cloned DNA. Pestic Sci 30: 456–458Google Scholar
  56. Waters LC, Zelhof AC, Shaw BJ, Ch’ang LY (1992) Possible involvement of the LTR of transposable element 17.6 regulating expression of an insecticide resistance-associated P450 gene in Drosophila. Proc Natl Acad Sci USA 89: 4855–4859PubMedCrossRefGoogle Scholar
  57. Weirich GF, Svoboda J A, Thompson MJ (1985) Ecdysone 20-monooxygenase in mitochondria and microsomes of Manduca sexta (L.) midgut: is the dual localization real? Arch Insect Biochem Physiol 2: 385–396CrossRefGoogle Scholar
  58. Wheelock GD, Scott JG (1990) Immunological detection of cytochrome P450 from insecticide resistant and susceptible house flies ( Musca domestica ). Pestic Biochem Physiol 38: 130–139CrossRefGoogle Scholar
  59. White RA Jr, Franklin RT, Agosin M (1979) Conversion of α-pinene to α-pinene oxide by rat liver and the bark beetle Dendroctonus terebrans microsomal fractions. Pestic Biochem Physiol 10: 233–242CrossRefGoogle Scholar
  60. Yu SJ (1986) Consequences of induction of foreign compound-metabolizing enzymes in insects. In: Brattsten LB, Ahmad S (eds) Molecular aspects of insect-plant interactions. Plenum, New York, p 153CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • R. Feyereisen

There are no affiliations available

Personalised recommendations