Steroid metabolism, Insect

Insect steroid metabolism has two biochemically distinctive components dealkylation of phytosterols to cholesterol and polyhydroxylation of cholesterol to ecdysone. We will focus on the first of these. Lacking the ability to synthesize sterols de novo, insects instead have evolved a dealkylation pathway to convert plant sterols to cholesterol(7-10). The dealkylation pathways are apparently absent in most other higher and lower organisms, which can convert mevalonate to squalene and thence into sterols( ). Specific insecticides are possible based on these biochemical differences. 

In a study concerning the insect steroid metabolism, Prestwich [72] developed the same strategy for the preparation of 29-fluorophytosterols 329 as depicted in Scheme 6.52. 

Svoboda J A 1984 Insect steroids Metabolism and function. In Nes W D, Fuller G, Tsai L-S (eds) Isopentenoids in plants Biochemistry and function. Marcel Dekker New York, 367-400... 

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. 

Arthropoda.—Steroid biosynthesis seems to be absent from all of this phylum. Examples of the class Arachnida, Diplopoda, Crustacea, and Insecta have been examined. Steroid metabolism in insects has been reviewed. " It should be borne in mind that insects can synthesise some terpenoids [e.g. (32) and (46)], but there is an absolute dietary requirement for steroids. Phytosterols such as -sitosterol are converted back into cholesterol derivatives apparently by the reverse of side chain alkylation (86 R = Et) (85 R = CHMe)—> (85 R = CHj)— (84)— (74). In addition a A -double bond is introduced. Parasites, and other organisms naturally present, may contribute to some of these reactions. ... 

Various aspects of steroid biosynthesis were included in a Royal Society Symposium. The published proceedings and other reviews have dealt with cyclase enzymes,water-soluble steroids and triterpenoids, the involvement of a 14(15)- or 8(14)-double bond and its reductionin cholesterol biosynthesis, biosynthesis of sterols, steroid metabolism in insects, pregnane steroids, cardenolides, and bufadienolides. ... 

The sterol requirements of invertebrates are frequently satisfied by modification of dietary steroids. Thus, cholesterol is formed from 24-alkylated steroids, such as ergosterol and /5-sitosterol, by Crustaceans and insects. The mechanism of this process seems to be the reverse of their mode of formation. The 24-ethyl group of -sitosterol is converted into a 24-ethylidene group with fucosterol, and cholesta-5,24-dienol is formed on loss of the alkyl group. Cholesterol is required in insects for metabolism to the hormone ecdysone (84). However, plants also produce ecdysone and both organisms metabolize cholesterol to ecdysone. which is then further metabolized to ecdysterone (85)." ... 

Variability in Steroid Metabolism Among Phytophagous Insects... 

SvoBODA, J. A. and M. J. Thompson, Variability in steroid metabolism among phytophagous insects, in Ecology and Metabolism of Plant Lipids (G. Fuller and W. D. Nes, eds.), ACS Symposium Series 325,176-186, American Chemical Society, Washington, DC, 1987. 

Resemblance of the tricyclic diterpene skeleton to the ABC-ring system of common steroids prompted the suggestion that the diterpenes interfered with the pink bollworm s steroid metabolism. Insect hormones are produced from dietary phytosterols which are absorbed, transported, and biochemically altered. Interference by the diterpene resin acids at any stage of this process could significantly reduce larval viability. To test this hypothesis, feeding studies were conducted using a levopimaric acid test diet with added cholesterol (addition of... 

Triterpenes and Steroids in Invertebrates Insects.—Terpenoid metabolism in insects will be considered separately from other invertebrates. Although insects do not possess the complete machinery required for biosynthesis of sterols from small molecules, it has been reported that a Sarcophaga bullata homogenate converts squalene into a compound with the chromatographic properties of squalene 2,3-oxide. However, this report warrants substantiation. The major insect juvenile hormone (133 R = Me) becomes labelled from [ C]acetate and also from l-[ H or... 

Cardenolldes appear to be metabolized by a variety of species, possibly as a mechanism for converting these steroids into compounds that can be efficiently sequestered. The milkweed bug, Oncopeltus fasclatus, metabolizes (hydroxylates ) the nonpolar cardenollde dlgltoxln to more polar compounds that are subsequently sequestered In the dorsolateral space fluid (17. 18). Larvae of another cardenolide-adapted Insect, the monarch butterfly, Danaus plexlppus. also convert these steroids Into compounds that are readily sequestered. For example, uscharldln, which contains a carbonyl group at C-3 ( ) of the... 

Physiological Function. The mechanism by which L-ascorbic acid benefits an insect is unknown. The vitamin is found in many tissues where it probably plays a variety of roles related to its redox potential. Besides the possible general function of detoxifying superoxide and hydrogen peroxide, L-ascorbic acid may be involved in metabolic processes such as tyrosine metabolism, collagen formation, steroid synthesis, detoxification reactions, phagostimulation, or neuromodulation. At this time one can only speculate about the function of vitamin C in some specific tissues. 

Several studies are available concerning the metabolism of steroids by insects. It is generally assumed that the Insecta do not synthesize steroids de novo but accumulate them from food this was neatly confirmed for the housefly as [ " CJcholesterol recovered from larvae had the same specific activity as that added to their diet. A... 

Our laboratory is concerned with targeting potential insecticides that disrupt normal development and metamorphosis in insects. Juvenile hormones (JHs), acting in concert with the steroid hormone ecdysone, are believed to control the timing of the larval-larval molts, larval-pupal and pupal-adult transformations of the insects. It has been demonstrated that the events leading to pupation are initiated by reduction of the JH titer in the hemolymph. In addition to a cessation of biosynthesis, this reduction in JH titer is controlled by degradative metabolism (16,17). Hydrolysis of the epoxide and ester functionalities present in active JH are two routes of degradation and subsequent inactivation of JH (18). The primary route of JH metabolism in the hemolymph of last stadium lepidopterous larvae is ester hydrolysis, and it is catalyzed by the enzyme juvenile hormone esterase (JHE). JHE has been shown to... 

A variety of steroidal natural products have been isolated from insects, even though, as mentioned previously, insects are not able to carry out de novo steroid biosynthesis. The steroidal nucleus, as it occurs in insect primary and secondary metabolites thus must ultimately come from dietary or symbiotic microbial sources. For many phytophagus insects, C28 and C29 phytosterols are converted into cholesterol (C27) through a series of dealkylation pathways, with cholesterol subsequently serving as the starting point for further metabolic transformations, and resulting in a wide variety of steroid-based natural products. In other cases, dietary phytosterols are sequestered and deployed unmodified, and as with other compound classes, the relative importance of dietary sequestration versus modification is not always clear. 

Occasionally, plant alkaloids of terpenoid origin are sequestered by insects. For example, larvae of many species of sawfly are chemically protected by toxic metabolites they sequester from their host plants. This includes iridoid glycosides (see Section 2.04.3) and a group of steroidal alkaloids produced by plants of the genus Veratrum, such as zygadenine (149). In some cases, sawfly larvae have been shown to further metabolize sequestered Veratrum alkaloids for example, zygadenine is derived from hydrolysis of the ester functionalities in sequestered protoveratrine A (150). ... 

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