Ecdysteroids metabolism

Keywords biosynthesis cardiac glycosides ecdysteroids metabolic pathways phylogeny pregnanes saponins secondary metabolites withanolides... 

Apparently, parasitic flatworms have discarded some pathways of de novo lipid synthesis, but have selectively retained several biosynthetic pathways that modify host lipids. Although lipids like fatty acids and cholesterol are obtained from the host, less abundant lipids that are more difficult to acquire because of their low concentration in the host (e.g. specific unsaturated fatty acids, eicosanoids, ecdysteroids and quinones) are synthesized de novo by the parasite, usually by the modification of more abundant substrates. In this way, lipid metabolism of parasitic flatworms is adapted to an opportunistic way of life, just like their energy metabolism. 

Unlike in dipterans, there is no ecdysteroid to complicate JH III action in adult bark beetles indeed, JH III appears to act alone in elevating HMG-R transcription in males. Furthermore, the clear, vigorous response by the mevalonate pathway in bark beetle midgut cells presents a simple metabolic focus, in contrast to the complicated developmental contexts studied in moths and flies. 

Recently, it has been demonstrated that ecdysteroid accumulation in spinach is inducible by mechanical [50] or insect [51] damage to roots. Evidence was further provided for the involvement of jasmonates in the induction of de novo ecdysteroid synthesis. Also, short- and long-term labelling of 20E from [2-14C]mevalonic acid in spinach demonstrate that ecdysteroids are metabolically stable in this species, which fits much better with a role in plant defence, rather than a phytohormonal role [52], Most recently, it has been demonstrated that root predation by the fungus gnat Bradysia impatiens results in elevated ecdysteroid levels in spinach and a significant reduction in larval establishment of B. impatiens [53],... 

Ecdysteroids suffer a number of disadvantages for applied purposes because they are chemically complex, environmentally and metabolically unstable and far too costly to isolate or synthesise in large amounts [150], Non-steroidal ecdysteroid analogues have greater potential for application in these respects. Further if such compounds are demonstrated to interact with the ecdysteroid-binding site of the EcR/USP complex, then analogues within these classes of compounds can be used to extend QSAR studies. 

The early literature on ecdysteroid structure-activity studies has been reviewed [120,150,171], The various bioassays employed vary in their complexity of performance and interpretation. A number of factors can affect the potency of a test compound to a greater or lesser extent depending on the assay system penetration, metabolism, excretion rate, sequestration and target site activity. In vivo assays will give a measure of all of these acting in concert, but not allow the individual contributions to be identified. On the other hand, cell-free receptor assays probably give a direct measure of target activity, but may bear little resemblance to the in vivo situation. 

Scheme 3). A clone of cells from the midge Cbironomus tentans was found to be resistant to the effects of ecdysteroids because they metabolized 20-hydroxyecdysone rapidly. The initial oxidation product was 20,26-dihydroxyecdysone, but this was oxidized further to 20-hydroxy-26-oxo-ecdysone (21). This aldehyde (21) then formed a tautomeric equilibrium mixture of two cyclic hemiacetals (22) and (23), which were separable, isolated, and their structures determined (Scheme 3) with the use of acetonides (Section 4.03.3.6).32 These are the first examples of ecdysteroids with side-chain hemiacetals. Although 20,26-dihydroxyecdysterone still... 

In addition to their well established role in catalyzing the metabolism of a wide variety of naturally occurring and synthetic xenobiotics, cytochrome P-450-mediated mixed-function oxidases are of critical Importance in the biosynthesis and regulation of the major hormones (ecdysteroids and juvenile hormone) that control insect growth and development. The characteristics of the mixed-function oxidases involved in the synthesis of insect hormones are described and the possibility that the enzymes might represent potential targets for insect control is discussed. 

To facilitate easy detection and improved separation, spacer components have been inserted between the members of the displacement train. The so-called Test Substance II (Camag, Muttenz, Switzerland) has numerous coloured components e.g., the Sudan Black components are members of the displacement train optimised for the ecdysteroids, semisynthetic morphine derivatives, and various phenylalkylamines. The various Sudan Black components were inserted between the components to be separated, if both the component and the ecdysteroids (or morphine derivatives or phenylalkylamines) were displaced. Black lines and white spots were observed, showing sharp separation and easy observation. In the case of the study of metabolism, the use of spacers facilitated the differentiation of poorly separated metabolites. 

A priori there is good reason to believe that inhibitors of CYP enzymes may influence the synthesis or degradation of ecdysteroids and juvenile hormones, and thus interfere with the normal development of insects this is the case. Piperonyl butoxide, a well-known CYP enzyme inhibitor that is widely used as a synergist for pyrethrins, retards the development of houseflies and other insects by a few days. The mechanism is probably an interference with the metabolism of JH and not JH activity. 

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