Cytochromes P450 of insects: the tip of the iceberg

Abstract

The cytochrome P450-dependent monooxygenases are an extremely important metabolic system involved in the metabolism of endogenous compounds and xenobiotics. Collectively, P450 monooxygenases can metabolize numerous substrates and carry out multiple oxidative reactions. The large number of substrates metabolized is due to the plethora of P450 isoforms and to the broad substrate specificity of some isoforms. Monooxygenases of insects have several functional roles, including growth, development, feeding and protection against xenobiotics, including resistance to pesticides and tolerance to plant toxins. This review begins with background information about P450s and their evolution, followed by a discussion of the extraordinary diversity of insect P450s. Given the enormous interest in studying individual P450s, we then provide a synopsis of the different methods that have been used in their isolation and the substrates that are known to be metabolized. We conclude by summarizing the lessons we have learned from the study of individual insect P450s, including their roles in insecticide resistance, plant-insect interactions and insect physiology. However, these studies are just the 'tip of the iceberg'. Our knowledge continues to expand at a rapid pace, suggesting that the next decade will outpace the last in terms of improving our understanding of the cytochromes P450 of insects.

Insights into the transcriptome of oenocytes from Aedes aegypti pupae

“…Additionally, different forms of P450s participate in the metabolism of different molecules, such as sterols, steroid hormones and several lipids that include eicosanoids, vitamin D3 and retinoid (Simpson 1997). In insects, P450s also participate in a variety of physiological roles ranging from development, feeding and growth to resistance to pesticides and tolerance to plant toxins (Scott & Wen 2001, Gilbert 2004. P450s are intimately involved in the synthesis and degradation of hormones and pheromones, such as 20-hydroxyecdysone and juvenile hormone (Scott & Wen 2001, Gilbert 2004).…”

“…In insects, P450s also participate in a variety of physiological roles ranging from development, feeding and growth to resistance to pesticides and tolerance to plant toxins (Scott & Wen 2001, Gilbert 2004. P450s are intimately involved in the synthesis and degradation of hormones and pheromones, such as 20-hydroxyecdysone and juvenile hormone (Scott & Wen 2001, Gilbert 2004). P450s expressed in oenocytes might participate in steroid metabolism, as previous data has demonstrated that oenocytes isolated from Tenebrio molitor larvae can synthesise both α and β ecdysone from 4-14 C-cholesterol precursors in vitro (Romer et al 1974).…”

“…In insects, increased transcription of P450s is frequently associated with resistance to insecticides (Scott & Wen 2001). High expression of P450s has been linked to insecticide resistance in Drosophila (Sundseth et al 1990) and An.…”

“…gambiae (Lycett et al 2006), and cytochrome b5 (corresponding to Ae. aegypti whole genome sequence AAEL010017) ( Table), that is an important donor of the regulating substrate that binds to P450 with CPR (Scott & Wen 2001).…”

Isolation of the monooxygenase complex from Rhipicephalus (Boophilus) microplus – clues to understanding acaricide resistance

“…Cytochrome P450s are an ancient protein family found in all forms of life (Scott and Wen 2001;Sztal et al, 2012) and are known to be the major phase I metabolizing enzymes. In humans, CYPs metabolize approximately 65% of currently used clinical drugs (Zhou et al, 2005), emphasising the importance of this group of enzymes in xenobiotic metabolism.…”