Prostaglandins and their precursors

Arachidonic acid is a slippery molecule that owes its mobility to its four cis double bonds. These are the source of its flexibility, keeping the pure fatty acid liquid, even at subzero temperatures, and helping to give mammalian cell membranes their correct fluidity at physiological temperatures. The double bonds are also the key to the propensity of arachidonic acid to react with molecular oxygen. This can happen nonenzymatically, contributing to oxidative stress, or through the actions of three types of oxygenase: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450. While the products of these enzymes and of the nonenzymatic transformations have well-substantiated bioactivities, unchanged arachidonic acid itself has biological activity. This will be a main focus this review. Before dealing with bioactivity, I will consider the solubility properties of the molecule, which are crucial to understanding the availability within the cell of endogenous and exogenous arachidonic acid. I then discuss two controversial issues, arachidonic acid transport into cells and the accessibility of added arachidonic acid to endogenous cellular compartments, and finally turn to selected biological actions of this lipid. The enzymes of arachidonic acid release have been well covered in specialized reviews and are introduced here only in passing.