By Friedrich Marks, Gerhard Fürstenberger
Polyunsaturated fatty acids are crucial for human mobilephone metabolism. As precursors of a truly huge and very flexible family members of signaling compounds they play a key function in intracellular verbal exchange. Eicosanoids represent probably the most ample and renowned subfamilies of those fatty acid derivatives that are shaped essentially alongside oxidative pathways. Prostaglandins, leukotrienes, and comparable eicosanoids have a modulatory functionality in mammalian cells and are answerable for tissue responses reminiscent of irritation or wound fix. expanding task in eicosanoid study sheds new gentle on state-of-the-art commonest ailments together with atherosclerosis, melanoma, Alzheimer's, asthma, and rheumatic illnesses. the new advances have already got far-reaching implications in drugs. This targeted account, written through major specialists, covers the ground-breaking advancements in contemporary eicosanoid learn. the themes span eicosanoid biogenesis, new points in their pathophysiology, for instance their effect at the cardiovascular method, in addition to the medical program of artificial eicosanoids and their antagonists. Researchers and scholars operating in biochemistry or in pharmaceutical, physiological, medicinal and neurochemistry will price this informative advent to at least one of the main quickly constructing fields in mobilephone biology.
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Additional info for Prostaglandins, Leukotrienes and Other Eicosanoids: From Biogenesis to Clinical Application
Oxygen insertion can also occur at C5 and C15 leading to isoprostane formation along a different pathway (dioxetane mechanism, see Rokach et al. 1891). In isoprostanes the two side chains of the five-membered ring are in the cis position rather than trans configurated as in cyclooxygenase-derived prostanoids. Compound IV is, therefore, the 8 stereoisomer (8-epi-PGFz,) of the cyclooxygenase-derived PGF2,. For more details about the complex stereochemistry of isoprostane formation see Rokach rt al.
Anandamide is rapidly degraded by hydrolysis catalyzed by a widespread microsoma1 aminohydrolase. In addition, it is rapidly taken up by cells through a mechanism which apparently resembles the reuptake of neurotransmitters by presynaptic terminals . 4 Eicosanoids in invertebrutes 27 Anandamide is also a substrate for the enzymes of eicosanoid biosynthesis such as 12- and 15-1ipoxygenases, cytochrome P-450-dependent monooxygenases and cyclooxygenases (see, for instance, Yu et al. [1061). At least 12(S)- and 15(S)-hydroxy anandamide, the lipoxygenase-derived metabolites, exhibit a similar affinity to the CB I receptor as anandamide .
E. histamine and the tetrapeptide FMRF amide, which, through activation of potassium channels, induce hyperpolarization and, thus, inhibit neurotransmitter release. Simultaneously with presynaptic inhibition, 12-lipoxygenase activity is induced in the neurons, pointing to the possibility that the corresponding eicosanoids may act as intracellular mediators of the neuromodulatory effect. In fact, treatment of such neurons with 12HPETE induced hyperpolarization, whereas 12-HETE and 5-HETE proved to be inactive.