Converting Membrane Components into Signaling Molecules


Upon cell stimulation, arachidonic acid is released from the plasma membrane through the activation of phospholi-pase A2 (PLA2). Further metabolism of arachidonic acid, and the eventual composition of resulting eicosanoids, depends upon the availability of enzymes responsible for arachidonic acid metabolism within a specific cell. These enzymes may be classified into three major groups, including the cyclooxygenases, lipoxygenases, and P450-monooxygenases (Figure 1).

The products of arachidonic acid metabolism exert a vast range of downstream effects on cell signaling pathways. The primary mode of eicosanoid action is through specific G protein—coupled receptors. In the highly complex network of cell signaling, these mediators influence many different systems, including those governing cell proliferation and differentiation (e.g., MAP kinase and PPARs), cytoskeletal dynamics (e.g., Rho GTPases), apoptosis (e.g., Akt and PI3K), ion transport (e.g., Ca2+ channels), and many others. Some of the eicosanoid downstream signaling pathways, such as those involved in inflammation, have been extensively studied. Others, such as the effects of metabolic pathways mediated by different cyclooxygenase isoforms, have only recently come under intense scrutiny.

The Cyclooxygenase Pathway

Prostaglandins and thromboxanes are bioactive substances that result from the metabolism of arachidonic acid by cyclooxygenases. These molecules are produced by most cells in the body and act as autocrine and paracrine mediators of a diverse range of cell functions, including pain

Plasma membrane phospholipids

Arachidonic acid

Phospholipase A2

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Essentials of Human Physiology

Essentials of Human Physiology

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