[Cyclooxygenase and prostanoids--biological implications].

Abstract

Arachidonic acid is the main precursor of eikosanoids, which regulate the function of various organs and systems. It is released from cellular membrane phospholipids by phospholipase A2 or indirectly by phospholipases C and D. Prostaglandins, prostacyclin (PGI2), and thromboxane A2 (TAX2) are synthesized from arachidonic acid on a metabolic pathway dependent on prostaglandin H2 synthase activity, also known as cyclooxygenase (COX). Of the 12 prostaglandins, the most potent are PGD2, PGE2, and PGF2. The others are synthesized in a primary step of arachidonic acid transformation (PGG2, PGH2), by degradation of the above-mentioned prostaglandins, or are not presented physiologically and may be chemically generated (PGK2, PGL2). Similar compounds could originate from dihomo-gamma-linolenic, alpha-linoleic, and eicosapentaenoic acids. Three primary COX isoenzymes are distinguished: COX-1 (constitutive), COX-2 (inducible), and COX-3, which is detected mainly in the central nervous system. A number of partial forms of COX-1 and COX-2 are also known, but their biological functions have not been well evaluated. Although they differ in genes, transcription factors, primary protein structure, reactivity to substrates, and drugs which inhibit enzyme activity, the crystal structure is similar for all the izoenzymes. In contrast to the COX-1 gene, whose expression is typical for most of the cells, constant COX-2 expression was detected in the placenta and fetal tissue in late pregnancy. In the postnatal period, COX-2 expression decreases rapidly physiologically, and is observed in kidney, forebrain, spinal cord, as well as some other organs, but to a minor degree. It increases in inflammatory, degenerative, and neoplastic processes.