Arachidonic acid, biochemical role

NSAIDs block the synthesis of COX products of arachidonic acid, which have a critical role in renal hemodynamics, control of tubular function, and renin release. It is now apparent that two isoforms of COX synthesize prostaglandins. COX-1 is a resident or constitutive form and COX-2 is an inducible form that increases with disorders of inflammation. NSAIDs are nonspecific inhibitors of both COX isoforms. Analgesic nephropathy is a common cause of ESRD in a number of countries, reaching 10% in Switzerland and Australia, but is essentially a preventable condition for which biochemical monitoring has proved useful. The incidence of this disease has decreased over the last decade as awareness has improved and phenacetin was withdrawn from over-the-counter analgesic mixtures. In the United States, 1 in 5 citizens (50 miflion) report that they use an... 

Ghosh J, Myers CE. Arachidonic acid stimulates prostate cancer cell growth critical role of Slipoxygenase. Biochem Biophys Res Commun. 235 (1997) 418-423. 

Rifkind, A.B., C. Lee, T.K. Chang, and D.J. Waxman (1995). Arachidonic acid metabolisms by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2 Regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Arch. Biochem. Biophys. 320, 380-389. 

Rifkind, A. B., M. Gannon, andS. S. Gross. 1990. Arachidonic acid metabolism by dioxin-induced cytochrome P-450 a new hypothesis on the role of P-450 in dioxin toxicity. Biochem. Biophys. Res. Commun. 172(3) 1180-88. 

Ghosh, J., and Meyers, CP. (1997) Arachidonic Acid Stimulates Prostate Cancer Cell Growth Critical Role of 5-Lipoxygenase, Biochem. Biophys. Res. Commun. 235,418-423. 

Over the past three decades, the metabolic pathways responsible for the storage, mobilization and metabolism of arachidonic acid in animal tissues have been studied in great detail. Many of the enzymes involved in these biochemical reactions have been characterized, and drugs that interfere with them have been described. Thousands of publications have documented the pharmacological actions exerted by arachidonic acid and its metabolites, collectively known as the eicosanoids, on all systems and organs of the body, as well as their possible physiological roles. 

---