1. Some naturally occurring fatty acids in animals

2. Phospholipases hydrolyze phospholipids
PLA2 will hydrolyze an arachidonate from the carbon-2 position of a membrane phospholipid in an immune response
Figure 9.8
Action of four phospholipases. Phospholipases A1, A2, C, and D can be used to dissect glycerophospholipid structure. Phospholipases catalyze the selective removal of fatty acids from C-1 or C-2 or convert glycerophospholipids to diacylglycerols or phosphatidates.
Phosphate ester linkage
Lipases are a class of hydrolase.

3. Arachidonic acid is a precursor to eicosanoids,
multi-functional hormones
Prostaglandins, Thromboxanes, and Leukotrienes

4. Eicosanoids
Eicosanoids are oxygenated derivatives of C20 polyunsaturated
fatty acids (e.g. arachidonic acid)- mediate many pathological
responses
20:4D5,8,11,14
Prostaglandin E2 – can cause constriction of blood vessels

5. Eicosanoids Thromboxane A2 – involved in blood clot formation
Leukotriene D4 – mediator of smooth-muscle contraction and
provokes bronchial constriction seen in asthmatics.
Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels.
Aspirin alleviates pain, fever, and inflammation by inhibiting
cyclooxygenase (COX), an enzyme critical for the synthesis of
Prostaglandins. (NSAID family of compounds)

6. An inhibitor of mammalian eicosanoid hormone synthesis
Advil (Ibuprofen)
An inhibitor of mammalian eicosanoid hormone synthesis

10. Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the synthesis of prostaglandins responsible for protection of the stomach lining, while COX-2 mediates the synthesis of prostaglandins responsible for pain and inflammation. By creating “selective” NSAIDs that inhibit COX-2, but not COX-1, the same pain relief as traditional NSAIDs is offered, but with greatly reduced risk of fatal or debilitating peptic ulcers. Rofecoxib is a selective COX-2 inhibitor or coxib (CycloOXygenase-2 Inhibitors).

11. Rofecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that has now been withdrawn over safety concerns. It was marketed by Merck & Co. to treat osteoarthritis and acute pain conditions. Rofecoxib was approved as safe and effective by the Food and Drug Administration (FDA) on May 20, 1999, and was subsequently marketed under the brand names Vioxx, Ceoxx, and Ceeoxx.
Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.
On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of $2.5 billion from Vioxx.