The Arachidonic Acid Pathway by drdoc on-line
 

The arachidonic acid pathway constitutes one of the main mechanisms for the production of pain and inflammation, as well as controlling homeostatic function.

The pathway produces different classes of end product :

1.
The prostaglandins (from cyclooxygenase metabolism) (PG) esp PGE2, PGF2alpha and PGD2 2. The Prostacyclines PGI2
3.. Thromboxane Tx A2
4.. The leukotrienes ( from lipoxygenase metabolism)

 

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The prostaglandins modulate immune function via the lymphocyte. They are mediators of the vascular phases of inflammation and are potent vasodilators. They increase vascular permeability. Prostacycline is a vasodilator and reduces platelet aggregation.

Thromboxane is a powerful vasoconstrictor and increases platelet aggregation.

 

The leukotrienes catalyze the addition of molecular oxygen to specific double bonds in polyunsaturated fatty acids. The most important lipoxygenases are the 5-1ipoxygenases. Products of the 5-lipoxygenase pathway are important mediators of inflammation.They cause vasoconstriction, but increase microvascular permeability. They are important mediators of bronchial asthma. They cause leukocyte adherence to the vascular endothelium and activate the leucocytes to secrete their enzymes. They contract smooth muscle - ie in the bronchi and blood vessels.

The pathway was first shown by Sir John Vane and colleagues - who proposed that the major therapeutic action of aspirin and other NSAIDs was from the inhibition of the enzyme cyclooxygenase. The anti-inflammatory potencies of the different NSAIDs were proportional to there action as cyclooxygenase inhibitors. It was also shown that cyclooxygenase inhibition produced toxic side effects. ie...NSAIDs cause erosive gastritis from the effects of reduction of PGE2 in the gastric mucosa. The renal toxicicty is also related to the action of cyclooxygenase inhibition.

In fact 2 kinds of COX enzymes are known now to exist. The COX 1 is related to the toxicity and COX 2 related to inflammation. Specific COX 2 inhibition is therefore desirable..and drugs are now commercially available - Celecoxib and Rofecoxib. (Go to COX1/COX2 page)

The poly unsaturated fats include omega-3 fatty acids. These polyunsaturated fatty acids compete with linoleic acid in the arachidonic acid pathway, thereby reducing the metabolism of arachidonic acid to prostaglandin E2 and thromboxane A2, which are both important in mediating inflammation.

Dietary sources of the omega-3 fatty acids and linolenic acid are salmon, mackerel, eels, nuts and vegetables. These acids inhibit the formation of the prostaglandin 2 series, and increase production of the 3 series prostaglandins and leukotrienes of the 5 series. Evening primrose oil contains gammalinolenic acid, an n-6 fatty acid which is converted to dihomogammalinolenic acid, an analogue of arachidonic acid. This may act as precursor to the prostaglandins of the 1 series, e.g, PGE, which has potent anti-inflammatory and anti-thrombotic action.

However, in terms of reducing the severity of inflammation, they do not appear to be of primary importance in the development of the disease.

The theoretical benefit has never been shown to produce any MAJOR therapeutic benefit--although there MAY BE A MARGINAL BENEFIT. I always encourage more fish and less red meat as part of the diet in patients with arthritis.

 

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