Hormone eicosanoid

The body uses a diverse range of chemical messengers to mediate and control growth, function and metabolism. These include hormones, eicosanoids and cytokines. Their effects may be evident throughout the body, or on the cell that synthesises them alone. They may affect one target or many targets about the body, in the same or sin different ways. 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

The release of arachidonate and the synthesis or interconversion of eicosanoids can be initiated by a variety of stimuli, including histamine, hormones such as epinephrine and bradykinin, proteases such as thrombin, and even serum albumin. An important mechanism of arachidonate release and eicosanoid syn-... 

Lipids are naturally occurring organic molecules that have limited solubility in water and can be isolated from organisms by extraction with nonpolar organic solvents. Fats, oils, waxes, many vitamins and hormones, and most nonprotein cell-meznbrane components are examples. Note that this definition differs from the sort used for carbohydrates and proteins in that lipids are defined by a physical property (solubility) rather than by structure. Of the many kinds of lipids, we ll be concerned in this chapter only with a few triacvlglycerols, eicosanoids, terpenoids, and steroids. 

The biosynthesis of eicosanoids utilizes several enzymes till the ultimate bioactive ligand is obtained. The literature is very rich in PAL studies on these enzymes and the local hormone receptors therefore only some major results on the key biotransformations and receptors are represented here. 

Hyperglycemia followed by hypoglycemia Catabolic hormones release Platelet-activating factor and eicosanoid release... 

Figure 11.30 Mechanisms of regulation of phospholipase A2. In all these processes described above, it is phospholipase A that carries out the hydrolysis of membrane phospholipid. Cytokines are local hormones produced by immune cells, T-lymphocytes and macrophages (Chapter 17). Other factors relate to shear stress in endothelial cells and those that stimulate release of granules from mast cells. Eicosanoids are present in the granules and they must be re-synthesised after degranulation in the mast cells. Here the enzymes described above must be present in mast cells.

Special tasks. Some lipids have adopted special roles in the body. Steroids, eicosanoids, and some metabolites of phospholipids have signaling functions. They serve as hormones, mediators, and second messengers (see p.370). Other lipids form anchors to attach proteins to membranes (see p.214). The lipids also produce cofactors for enzymatic reactions—e.g., vitamin K (see p.52) and ubiquinone (see p.l04). The carotenoid retinal, a light-sensitive lipid, is of central importance in the process of vision (see p.358). 

Cyt P450 systems are also involved in many other metabolic processes—e.g., the biosynthesis of steroid hormones (see p. 172), bile acids (see p. 314), and eicosanoids (see p. 390), as well as the formation of unsaturated fatty acids (see p. 409). The liver s reddish-brown color is mainly due to the large amounts of P450 enzymes it contains. 

T FIGURE 10-18 Arachidonic acid and some eicosanoid derivatives. (a) In response to hormonal signals, phospholipase A2 cleaves arachidonic acid-containing membrane phospholipids to release arachidonic acid (arachidonate at pH 7), the precursor to various eicosanoids. (b) These compounds include prostaglandins such as PCE, in which C-8 and C-12 of arachidonate are joined to form the characteristic five-membered ring. In thromboxane A2/ the C-8 and... 

Prostaglandins, thromboxanes, and leukotrienes (the eicosanoids), derived from arachidonate, are extremely potent hormones. 

Mammals have several classes of hormones, distinguishable by their chemical structures and their modes of action (Table 23-1). Peptide, amine, and eicosanoid hormones act from outside the target cell via surface receptors. Steroid, vitamin D, retinoid, and thyroid hormones enter the cell and act through nuclear receptors. Nitric oxide also enters the cell, but activates a cytosolic enzyme, guanylyl cyclase (see Fig. 12-10). 

Hormones can also be classified by the way they get from the point of their release to their target tissue. Endocrine (from the Greek endon, within, and krinein, to release ) hormones are released into the blood and carried to target cells throughout the body (insulin is an example). Paracrine hormones are released into the extracellular space and diffuse to neighboring target cells (the eicosanoid hormones are of this type). Autocrine hormones are released by and affect the same cell, binding to receptors on the cell surface. 

Eicosanoids The eicosanoid hormones (prostaglandins, thromboxanes, and leukotrienes) are derived from the 20-carbon polyunsaturated fatty acid arachidonate. 

Peptide, amine, and eicosanoid hormones act outside the target cell on specific receptors in the plasma membrane, altering the level of an intracellular second messenger. 

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