Hormone biosynthetic pathways

Abstract Pheromones are utilized by many insects in a complex chemical communication system. This review will look at the biosynthesis of sex and aggregation pheromones in the model insects, moths, flies, cockroaches, and beetles. The biosynthetic pathways involve altered pathways of normal metabolism of fatty acids and isoprenoids. Endocrine regulation of the biosynthetic pathways will also be reviewed for the model insects. A neuropeptide named pheromone biosynthesis activating neuropeptide regulates sex pheromone biosynthesis in moths. Juvenile hormone regulates pheromone production in the beetles and cockroaches, while 20-hydroxyecdysone regulates pheromone production in the flies. 

Keywords Pheromone Biosynthetic pathways Hormonal regulation PBAN ... 

Fig. 3 Biosynthetic pathways to pyrethrins. The identified enzymes involved in biosynthesis are shown in orange. Note that green leaf volatiles and the plant hormone jasmonic acid share the oxylipin pathway. The phosphate moiety is indicated as P ...

The chemical communication system used to attract mates involves not only the overt chemical signals but also indirectly a great deal of chemistry in the emitter and receiver. As an example, in emitting female moths, this includes enzymes (and cofactors, mRNA, genes) of the pheromone biosynthetic pathways, hormones (and genes) involved in... 

For an organism to eliminate a lipophilic, chemically inert xenobiotic, it is usually hrst necessary to oxidize it to a more polar form. In addition, many biosynthetic pathways that produce steroid hormones, prostaglandins, leukotrienes, etc. involve oxidative steps. Organisms have evolved many enzymes to carry out these oxidations. Oxidation can occur by addition of oxygen (without addition of hydrogen which would represent hydration), removal of hydrogen atoms (without removal of oxygen which would represent dehydration), or simply removal of electrons. 

Urea ((NH2)2CO), a small and highly water soluble molecule, is an end product of amine and ammonia nitrogen metabolism and as such represents an example of biodetoxification (Section 6.4). The process is discussed in this section because it illustrates a genuine de novo biosynthetic pathway rather than detoxification involving chemical modification, via phase I and phase II reactions, of a pre-existing molecule as is the case for haem or steroid hormones. 

Biosynthetic pathways. Only an overview of the synthesis pathways that lead to the individual hormones is shown here. Further details are given on p.410. 

Hydrophilic hormones and other water-soluble signaling substances have a variety of biosynthetic pathways. Amino acid derivatives arise in special metabolic pathways (see p. 352) or through post-translational modification (see p. 374). Proteohormones, like all proteins, result from translation in the ribosome (see p. 250). Small peptide hormones and neuropeptides, most of which only consist of 3-30 amino acids, are released from precursor proteins by proteolytic degradation. 

The first committed step in the synthesis of triterpenoid saponins involves the cyclisation of 2,3-oxidosqualene to give one of a number of different potential products [9]. Most plant triterpenoid saponins are derived from oleanane or dammarane skeletons, although lupanes are also common [9]. This cycHsation event forms a branchpoint with the sterol biosynthetic pathway, in which 2,3-oxidosqualene is cyclised to lanosterol (in animals and fungi) or to cycloartenol (in plants) (Fig. 2). Sterols are important membrane constituents and also serve as precursors for hormone biosynthesis. 

We begin with an account of the main steps in the biosynthesis of cholesterol from acetate, then discuss the transport of cholesterol in the blood, its uptake by cells, the normal regulation of cholesterol synthesis, and its regulation in those with defects in cholesterol uptake or transport. We next consider other cellular components derived from cholesterol, such as bile acids and steroid hormones. Finally, an outline of the biosynthetic pathways to some of the many compounds derived from isoprene units, which share early steps with the pathway to cholesterol, illustrates the extraordinary versatility of isoprenoid condensations in biosynthesis. 

At each level of a hormonal cascade, feedback inhibition of earlier steps in the cascade is possible an unnecessarily elevated level of the ultimate hormone or of one of the intermediate hormones inhibits the release of earlier hormones in the cascade. These feedback mechanisms accomplish the same end as those that limit the output of a biosynthetic pathway (compare Fig. 23-11 with Fig. 6-28) a product is synthesized (or released) only until the necessary concentration is reached. 

FIGURE 23-11 Cascade of hormone release following central nervous system input to the hypothalamus. In each endocrine tissue along the pathway, a stimulus from the level above is received, amplified, and transduced into the release of the next hormone in the cascade. The cascade is sensitive to regulation at several levels through feedback inhibition by the ultimate hormone. The product therefore regulates its own production, as in feedback inhibition of biosynthetic pathways within a single cell. 

Ethylene is now considered to be one of the main plant-hormones involved in fruit development. Many responses formerly believed to result from the presence of auxins are now ascribed to induced ethylene production.425 The biosynthetic pathway for formation of ethylene from methionine, in a wide variety of plant tissues, including shoots of mung bean,426 tomato,427 and pea427 carrot427 and tomato428 roots and the fruits of apple,429,430 tomato,427 and avocado,427 has been elucidated, and is as follows. 

Figure 25-12 Structures and some biosynthetic pathways for some hormones, indole alkaloids, and other metabolites of tryptophan.

Stereospecific 2,3-epoxidation of squalene. followed by a non-concerted carbocationic cyclization and a seiies of carbocationic rearrangements, forms lanosterol (26) in the first steps dedicated solely toward steroid synthesis. Cholesterol is the principal starting material for steroid hormone biosynthesis ill animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to he normal constituents, in trace amounis. in tissues that are actively synthesizing cholesterol,... 

The excessive production of thyroid hormone in Graves disease is associated with an enlarged thyroid gland, but in this case a circulating immunoglobulin that mimics the activity of thyroid stimulating hormone (TSH) is implicated. Finally, we saw in an earlier section how an inappropriate steroid hormone may be secreted in excessive amounts when specific enzymes in the adrenal steroid biosynthetic pathway are present at inadequate levels. 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

---