Tất cả các màng tế bào, bao gồm những nội mô phổi, bao gồm một phần lớn của các phospholipid cấu trúc có nguồn gốc từ glycerol. Ngoài ra để phục vụ một chức năng hàng rào, những hợp chất này được chuyển hóa bởi một gia đình Phospholipases, giải thoát các tiền chất của các hợp chất hoạt tính sinh học | Chapter 13 Eicosanoids and the Pulmonary Microvasculature Ivan M. Robbins and Brian W. Christman Department of Medicine Division of Allergy Pulmonary and Critical Care Medicine Vanderbilt University School of Medicine Tennessee Introduction All cell membranes including those of the pulmonary endothelium are composed in large part of phospholipids structurally derived from glycerol. In addition to serving a barrier function these compounds are metabolized by a family of phospholipases which liberates precursors of biologically active compounds that act in both an endocrine and paracrine fashion to alter physiologic responses. These phospholipids are enriched in the sn-2 position with arachidonic acid a 20-carbon alkane with four double bonds. Metabolism of arachidonic acid proceeds by oxygen insertion catalyzed by several different enzyme families including cyclooxygenase 1 COX-1 and cyclooxygenase 2 COX-2 yielding an unstable intermediate prostaglandin pG H2. Further metabolism of this compound depends on the complement of available enzymes in a given cell type . prostacyclin synthetase in endothelial cells and thromboxane synthase in platelets but can result in formation of a variety of prostaglandins including PGD2 PGE2 PGF2a prostacyclin pGI2 and TxA2. In the vascular bed of the lung the predominant prostaglandins made by vascular endothelium are prostacyclin and PGE2. Smooth muscle cells in lung vessels are net producers of both thromboxane A2 and prostacyclin. It is also possible for arachidonic acid to be metabolized by lipoxygenases yielding leukotrienes and lipoxins and specific cytochrome P450 enzymes yielding epoxyeicosatrienoic acids EETs and stereospecific hydroxyeicosatetraenoic acids HETEs . Alternately during situations of enhanced oxidant stress reactive oxygen species can directly interact with arachidonic acid esterified to membrane phospholipids to form isoprostanes IsoPs compounds analogous to prostaglandins but with different stereochemistry
