Neonicotinoid metabolism: compounds, substituents, pathways, enzymes, organisms, and relevance.
Neonicotinoids are one of the three principal insecticide chemotypes. The seven major commercial neonicotinoids are readily biodegraded by metabolic attack at their N-heterocyclylmethyl moiety, heterocyclic or acyclic spacer, and N-nitroimine, nitromethylene, or N-cyanoimine tip. Phase I metabolism is largely dependent on microsomal CYP450 isozymes with situ selectivity in hydroxylation, desaturation, dealkylation, sulfoxidation, and nitro reduction. Cytosolic aldehyde oxidase is a nitroreductase for some neonicotinoids. Phase II metabolism involves methylation, acetylation, and formation of glucuronide, glucoside, amino acid, and sulfate- and glutathione-derived conjugates. Some neonicotinoids act as proinsecticides with metabolism to more potent nicotinic agonists. Pest resistance is more commonly due to synergist-reversible CYP450 detoxification than to nAChR mutants or variants. Metabolites in some cases contribute to mammalian hepatotoxicity and carcinogenesis and in others to enhanced plant vigor and stress shields. These relationships explain much of neonicotinoid comparative toxicology and provide the basis for continued and improved safety and effectiveness of this chemotype.
Casida
John E
JE
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA. ectl@berkeley.edu
D042931:Aldehyde Oxidase / Q000378:metabolism; D000691:Anabasine / Q000819:agonists*; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D001673:Biodegradation, Environmental; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D007313:Insecta / Q000201:enzymology; D007305:Insecticide Resistance; D007306:Insecticides / Q000378:metabolism*; D008958:Models, Molecular; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000378:metabolism; D011978:Receptors, Nicotinic
D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; C082359:imidacloprid; D003577:Cytochrome P-450 Enzyme System; D042931:Aldehyde Oxidase; D000691:Anabasine