Insects, metabolism, species differences

Insects utilize propionate and methylmalonate in the biosynthesis of ethyl branched juvenile hormones and methyl branched cuticular hydrocarbons. The sources of propionate and methylmalonate in some insects appear to differ from those in mammals. Succinate is the precursor of propionate and methylmalonate in a termite, whereas valine and probably other amino acids are the sources of propionate and methylmalonate in several other species. An unusual pathway for propionate metabolism has been shown to occur in insects and it may be related to the absence or low levels of vitamin B found in many species. Propionate is converted directly to acetate with carbon 1 of propionate lost as C02> carbon 2 of propionate becoming the methyl carbon of acetate and carbon 3 of propionate becoming the carboxyl carbon of acetate. This pathway suggested the possibility that 2-fluoropropionate might be selectively metabolized in insects to the toxic 2-fluoro-acetate. However, preliminary data indicate that 2-fluoropropionate is not toxic to the housefly or the American cockroach. 

Advantage of species differences in metabolism was taken with the synthesis of malathion which is attacked by esterases in mammals and excreted rapidly as the diacid before conversion of the innocuous thio-phosphate to the toxic phosphate. Insects have very low levels of esterases, and metabolism to the lethal oxo metabolite can occur unimpeded (Figure 20). 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Amidases can be found in all kinds of organisms, including insects and plants [24], The distinct activities of these enzymes in different organisms can be exploited for the development of selective insecticides and herbicides that exhibit minimal toxicity for mammals. Thus, the low toxicity in mammals of the malathion derivative dimethoate (4.44) can be attributed to a specific metabolic route that transforms this compound into the nontoxic acid (4.45) [25-27]. However, there are cases in which toxicity is not species-selective. Indeed, in the preparation of these organophosphates, some contaminants that are inhibitors of mammalian carboxylesterase/am-idase may be present [28]. Sometimes the compound itself, and not simply one of its impurities, is toxic. For example, an insecticide such as phos-phamidon (4.46) cannot be detoxified by deamination since it is an amidase inhibitor [24],... 

There exists evidence that some insects store dietary alkaloids derived from natural sources. Figure 98 presents insect species that are known to accumulate pyrrolizidine alkaloids during different developmental stages. The larvae and adults of these insects can metabolize pyrrolizidine alkaloids in current physiological activities. These alkaloids are not toxic for these organisms. Moreover, there is observed trace accumulation of a portion of these compounds in the liver. There is no definitive purpose for these traces. Generally, the opinion presented in 1888 by Stahl in Germany that the accumulation of alkaloids is for defensive purposes has been most often cited in the research literature. 

The nutritional requirements of insect species exhibiting different feeding habits like scavengers, parasites, predators and phytophagous insects, are similar in a qualitative sense (O. Each insect species needs, however, a particular quantitative composition of nutrients in its diet to complete development ( ). The presence of toxic substances in plants, secondary plant substances as they were formerly called by phytochemists, forms a barrier which phytophagous insects have overcome by specialization. Thus, an insect can tolerate or detoxify the secondary plant substances present in its host plants, while the majority of these substances being present in other plants still acts as toxins (J ). In this way phytophagous insects are adapted to the metabolic qualities of their host plants, i.e. a particular chemical composition of nutrients and secondary plant substances. 

Hydrolytic reactions. There are numerous different esterases responsible for the hydrolysis of esters and amides, and they occur in most species. However, the activity may vary considerably between species. For example, the insecticide malathion owes its selective toxicity to this difference. In mammals, the major route of metabolism is hydrolysis to the dicarboxylic acid, whereas in insects it is oxidation to malaoxon (Fig. 5.12). Malaoxon is a very potent cholinesterase inhibitor, and its insecticidal action is probably due to this property. The hydrolysis product has a low mammalian toxicity (see chap. 7). 

The onset of symptoms depends on the particular organophosphorus compound, but is usually relatively rapid, occurring within a few minutes to a few hours, and the symptoms may last for several days. This depends on the metabolism and distribution of the particular compound and factors such as lipophilicity. Some of the organophosphorus insecticides such as malathion, for example (chap. 5, Fig. 12), are metabolized in mammals mainly by hydrolysis to polar metabolites, which are readily excreted, whereas in the insect, oxidative metabolism occurs, which produces the cholinesterase inhibitor. Metabolic differences between the target and nontarget species are exploited to maximize the selective toxicity. Consequently, malathion has a low toxicity to mammals such as the rat in which the LD50 is about 10 g kg-1. 

The following are some examples Phase 1 aromatic hydroxylation of aniline varies with species, the metabolism of malathion differs between mammals and insects, and the metabolism of amphetamine varies between different mammalian species. 

The genomes and the metabolism of the two insects Drosophila melanogaster and Anopheles gambia370a can now be compared. Many differences can be seen but almost half of the genes are orthologs. Many of these can be related also to those of pufferfish, mice,3700 humans, and other species. 

As reviewed by Williams (43), ecdysone has been isolated from more than 10 species of conifers, 20 ferns, and 30 flowering plants (out of 1000 species surveyed). A total of 28 different plant ecdysones are known, the most ubiquitous being /3-ecdysone. The ecological significance of /3-ecdysone in plants is unclear. It is not toxic when orally ingested (as feeding larvae would obtain it from a food plant), but there is some evidence that it could be a feeding deterrent in concentrations as low as 1 ppb. Perhaps it serves as a steroid base for other compounds once it is in an insect s metabolic system. 

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