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Prof. Eric Arnoys

COX1 and COX2

Prostaglandins and thromboxanes are potent paracrine hormones responsible for a diverse array of physiological effects, including from inflammation, platelet aggregation, vasodilation, vasoconstriction, and smooth muscle relaxation. They are made from arachidonate that has been released from a glycerophospholipid by an activated phospholipase A2:


Structure of arachidonate, aka, eicosatetraenoate 20:4 (Δ5,8,11,14) (file obtained from

The first steps in both prostaglandin and thromboxane synthesis are catalyzed by cyclooxygenase (COX), an enzyme with both peroxidase and cyclooxygenase activities. A heme in the core of the enzyme is responsible for the addition of an oxygen molecule in the first step of the reaction:


As one might expect with their role in inflammation, prolific activity of prostaglandins and thromboxanes is found in excessive swelling and in chronic arthritis. In fact, COXs are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. Just how they are targeted became clear when the structures of the COXs were solved.


Once arachidonate is released from the phospholipid, it navigates this channel to the heme in the first active site.


Most NSAIDs, such as celecoxib shown here, act as competitive inhibitors by blocking this channel. Aspirin is unusual in that it acetylates a serine in the channel which permanently inactivates the enzyme.

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Minor in Biochemistry

Minor in Chemistry


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