What is the physiology of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2)?

Answer

Evidence suggests that COX-1 and COX-2 are similar in structure and function but that they exist as 2 distinct enzymatic entities. They have been defined as monotropic integral membrane proteins located primarily in the endoplasmic reticulum (COX-1) and the perinuclear envelope (COX-2). Their distinct biosynthetic activity includes an endoperoxidase synthase reaction that oxygenates and cyclizes polyunsaturated fatty acid precursors (eg, arachidonic acid) to form prostaglandin G₂ (PGG2), and a peroxidase reaction that converts PGG2 to prostaglandin H₂ (PGH2), as shown below. In turn, PGH2 is converted to biologically active products (ie, prostaglandin E₂ [PGE2]) by individual synthase and reductase reactions.

Cyclooxygenase conversion of arachidonic acid into prostaglandin H2 (PGH2).

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COX-1 is expressed constitutively and is isolated throughout most cell lines in almost all mammalian tissues. It is described as a housekeeping enzyme, being responsible for cell-to-cell signaling, tissue homeostasis, and cytoprotection. In view of this, researchers hypothesize that COX-1 is a rapid responder to various physiologic conditions.

Conversely, COX-2 is described as an inducible isoform influenced by a plethora of proinflammatory mediators. Without appropriate stimulation, isolation of the COX-2 protein is negligible in most tissues. However, newer literature reveals that COX-2 is expressed constitutively in some cell lines of the brain, kidney, and trachea. Although vaguely described, COX-2 is considered to be a principal mediator of inflammation, mitogenesis, and angiogenesis.

Studies have demonstrated that the eicosanoids produced by cytosolic COX-1 participate in autocrine and paracrine activities, while those produced by perinuclear COX-2 result in intracrine activity. This subcellular localization of the COX enzyme (through the use of new microscopy techniques) has helped to explain why 2 isoforms exist. Furthermore, researchers have proposed that COX-1 and COX-2 acquire arachidonic acid from different phospholipases, suggesting participation through separate pathways.

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Twenty-carbon polyunsaturated fatty acid with cyclopentane ring.
Cyclooxygenase conversion of arachidonic acid into prostaglandin H2 (PGH2).
Thromboxane A2 (TXA2).
Prostacyclin (PGI2).
Prostaglandin E2 (PGE2).

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