Arachidonic acid cascade enzymes

The arachidonic acid cascade enzymes represent a collective group of oxygenases, primarily including cyclooxygenases (COX-1, COX-2), lipoxygenases (5-LOX, 12-LOX, 15-LOX), and cytochrome P450 (CYP) epoxygenases/hydroxylases, which metabolize 20-carbon polyunsaturated fatty acids (PUFAs) into bioactive lipid mediators [PMID: 21473700]. While arachidonic acid (AA) is the primary endogenous substrate leading to pro-inflammatory eicosanoids like prostaglandins and leukotrienes, these enzymes also utilize omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as alternative substrates [PMID: 22591890]. The competition between AA and omega-3 PUFAs for these enzymes shifts the lipid profile toward less inflammatory or specialized pro-resolving mediators (SPMs), such as resolvins and protectins, which actively promote the resolution of inflammation [PMID: 24563426]. These enzymes are critical regulators of vascular tone, platelet aggregation, and immune cell recruitment, making them central to the pathophysiology of asthma, cardiovascular disease, and chronic inflammatory conditions like rheumatoid arthritis [PMID: 20156990]. Pharmacological intervention typically involves direct inhibition of these enzymes, as seen with nonsteroidal anti-inflammatory drugs (NSAIDs) targeting COX or zileuton targeting 5-LOX, to alleviate pain and inflammatory symptoms [PMID: 17301243].

Other names

Eicosanoid biosynthetic enzymesArachidonate oxygenasesCOX/LOX/CYP pathwayProstaglandin-endoperoxide synthases

Inhibition of cyclooxygenase or lipoxygenase activity to reduce the production of pro-inflammatory eicosanoids; competition by omega-3 PUFAs for enzyme active sites.