Biosynthesis of prostaglandins

The generation of prostaglandins is catalyzed by a membrane-bound multienzyme complex. The first reaction of the biosynthetic sequence is the generation (by the enzyme 'fatty acid cyclooxygenase') of prostaglandin endoperoxides, a reaction which involves the incorporation of two moles of oxygen: this reaction probably proceeds by an ene reaction rather than a free-radical mechanism. After biosynthesis the endoperoxides can be metabolized in various ways depending on the cell-type. For example, in platelets they may be transformed into non-prostanoid compounds called thromboxanes, whereas vascular endothelium and many other tissues generate another derivative, prostacyclin. In other tissues, the 'classical' prostaglandins E, F or D may be generated. Some products of the cyclooxygenase (e.g. hydroperoxides, malonaldehyde) may have a direct toxic action on cells: prostaglandins themselves do not, but some types (especially those of the E series) are probably responsible for many of the clinical signs and symptoms of inflammation.