Clinical Correlations of Eicosanoid Metabolism

A. Cyclooxygenase (COX) localization – COX I and COX II are located on the luminal faces of endoplasmic reticulum (ER) membranes, and on the intermembrane faces of the nuclear envelope (NE). (The bilaminar (double) NE is continuous with the ER.) In contrast to most integral membrane proteins, such as glucagon and epinephrine receptors and the LDL receptor, COX I and COX II do not pass through membranes. They are said to be monotopically inserted into membranes, and are exposed on only one side, in this case the luminal side, of the membrane. Eicosaenoic acids (cyclooxygenase substrates such as arachidonic acid) reach the COX active site by diffusing through a short patch of membrane into a “protein tunnel” that is part of the enzyme-membrane contact region. Differences in the structure of this tunnel in COX I and COX II have contributed to the design of specific inhibitors.