Advance in Understanding the Biosynthesis of Prostacyclin and Thromboxane A2 in the Endoplasmic Reticulum Membrane via the Cyclooxygenase Pathway

Recent advances in topological and structural characterization of the prostacyclin (PGI2) and thromboxane A2 (TXA2) synthases have led to the understanding of the biosynthesis of PGI2 and TXA2 at a structural level. This mini-review focuses on the molecular mechanism of the isomerization of the prostaglandin H2 to PGI2 and TXA2 by their synthases in the endoplasmic reticulum (ER) membrane coordinated with cyclooxygenase-1 or -2. This review summarizes the evidences in which the biosynthesis of PGI2 and TXA2 are influenced / modulated by the membrane anchor residues of the synthases and the ER membrane itself, and provides the structural basis for engineering the synthases for the next generation of gene therapy and drug designs targeting the specific synthases.