Prostaglandins and Leukotrienes

Abstract

Prostaglandins and leukotrienes are different types of eicosanoids – oxygenated, 20 carbon fatty acids synthesized from arachidonic acid (AA) (all cis-5,8,11,14-eicosatetraenoic acid). AA is a member of the n-6 family of fatty acids that are essential for mammals. There are three major groups of eicosanoids formed via three distinct pathways – the cyclooxygenase (COX), lipoxygenase, and epoxygenase pathways. These pathways occur in higher eukaryotes that contain highly unsaturated fatty acids. Prostanoids, which include the prostaglandins and thromboxanes, are formed through the COX pathway; leukotrienes and related hydroxy fatty acids come from the lipoxygenase pathway; and epoxy and dihydroxy acids are formed via epoxygenase (P450) pathways. Prostanoids and leukotrienes function through G-protein-linked receptors and perhaps through peroxisomal proliferator-activated receptors, and there are one or more protein receptors for each prostanoid and leukotriene. These compounds act locally near their sites of synthesis without entering the circulation. They coordinate intercellular communication between the same (autocrine) and different (paracrine) cell types. Prostanoids promote inflammation, thrombosis, and pain, whereas leukotrienes are involved in asthma. Nonsteroidal anti-inflammatory drugs such as aspirin, ibuprofen, and COX-2 inhibitors function by attenuating prostanoid synthesis while inhibitors of leukotriene synthesis and action such as zileuton and montelukast, respectively, are used to treat asthma.