Metabolism of Eicosanoids

EFA deficiency can also occur in infants with highly restricted diets (e.g., primarily skim milk intake), in patients receiving total parenteral hyperalimentation without supplements of unsaturated lipids, and in those with severe malabsorptive defects. 

In EFA deficiency, oleic acid can be dehydrogenated to yield polyunsaturated fatty acids (PUFAs) that are nonessential and do not substitute for the essential fatty acids. One suchPUFA is 5,8,11-eicosatrienoic acid, which occurs in significant amounts in heart, liver, adipose tissue, and erythrocytes of animals fed diets deficient in EFAs but decreases after supplementation with linoleic or linolenic acids. Its appearance in tissues and plasma has been used in the assessment of EFA deficiency. 

40-45%), with equal amounts of saturated, monounsatu-rated, and polyunsaturated fats, and a cholesterol intake of no more than 300 mg/day (current average consumption in North America is about 600 mg/day). 

The eicosanoids—prostaglandins (PGs), thromboxanes (TXs), prostacyclins (PGIs), and leukotrienes (LTs)—are derived from essential fatty acids and act similarly to hormones (Chapter 30). However, they are synthesized in almost all tissues (unlike hormones, which are synthesized in selected tissues) and are not stored to any significant extent their physiological effects on tissues occur near sites of synthesis rather than at a distance. They function as paracrine messengers and are sometimes referred to as autacoids. 

Fatty Acid Composition of Some Fats of Animal and Plant Origin 

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It is misleading to consider that ROS are always deleterious, and that to prevent release or action of ail ROS will be of therapeutic value. One could reason that some ROS are released without control or purpose, as by-products of the normal metabolism of eicosanoids, or during oxidative phosphorylation in the mitochondria. However, during normal function, inflammatory ceUs appropriately release ROS both intracellularly into vacuoles and extracellularly in order to kill foreign organisms in host defence. Also, nitric oxide is a radical species whose principal role in the lung appears to be the control of pulmonary vascular tone and platelet function. Nevertheless, there are clear examples where fhistrated phagocytosis could explain an excessive release of ROS in... 

Yamamoto S (1999) Biosynthesis and metabolism of eicosanoids. Comprehensive Natural Products Chemistry, Vol 1. Elsevier, Amsterdam, pp 255-271. 

Additional deleterious or beneficial actions of agents that alter the metabolism of eicosanoids are described in the following text ... 

Prior to the demonstration of AA metabolism by P450, several groups demonstrated the role of microsomal P450s in the o>/a)-l hydroxylation of prostanoids "- and, more recently, leukotrienes- . Most of these reactions are considered to be involved in eicosanoid catabolism and excretion, but their potential relevance in eicosanoid bioactivation or inactivation, and/or in the control of organ/cell eicosanoid levels has only begun to be explored. We will first discuss the role of P450 in the metabolism of eicosanoids, and then concentrate on the studies of its role in AA metabolism and bioactivation. 

Typically, the P450-dependent metabolism of eicosanoids results in the hydroxylation of their... 

In the first part the biosynthesis of fatty acids in skin with its role in barrier function as well as the role of dietary fatty acids on skin cell function and in the treatment of inflammatory skin diseases is presented. The second part deals with skin as a source of proinflammatory eicosanoids, especially with the keratinocyte as a major cellular source. Metabolism of eicosanoids in skin, its role in psoriasis and atopic dermatitis as well as pharmacological inhibition of eicosanoid biosynthesis is reviewed. 

CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vaso-dilatory, and fibrinolytic properties. Polymorphic alleles with reduced function are known. Some other CYP2 subfamilies and isozymes listed in Table 1 are still not well characterized, in part because most of them were discovered in the course of the human genome project. 

Stratmann K, Boland W, Muller DG (1992) Pheromones of marine brown algae a new branch of eicosanoid metabolism. Angew Chem Int Ed 3 1246-1248 Suzuki M, Matsuo Y, Takahashi Y, Masuda M (1995) Callicladol, a novel cytotoxic bromotriter-pene polyether from a Vietnamese species of the red algal genus Laurencia. Chem Lett 11 1045-1046... 

In addition to its effects on haematopoietic cells, GM-CSF can also affect the function of mature cells. GM-CSF treatment increases the survival, cytotoxicity and eicosanoid formation by eosinophils, and can increase the tu-mouricidal activity, cytokine expression, surface antigen expression and oxidative metabolism of macrophages. It is chemotactic for endothelial cells, can induce the proliferation of some tumour cells, stimulates histamine release from basophils and affects the viability and function of Langerhans cells. Its effects on mature neutrophils are described in 7.2.1, 7.3.4. 

Nitric oxide and eicosanoid synthesis haem synthesis. The importance of the pentose phosphate pathway reduced glutathione in maintaining red cell integrity. The respiratory burst in phagocytes. Clotting and complement enzyme cascades. Metabolism of lipoproteins. 

Common NSAIDs include aspirin, ibuprofen, indomethacin, naproxen, and ketoprofen. Even though anti-inflammatories generally target cyclooxygenase, there are apparent differences in the details of how they relieve pain. For example, aspirin acts by primarily inhibiting the COX-dependent synthesis of eicosanoids, which are end products of metabolism of essential fatty acids including prostaglandin... 

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