Biochem

CYCLOOXYGENASE (COX)

Aeyanica Bianca D. Morales

HUB32

De La Salle University-Dasmariñas

Dasmariñas, Cavite Philippines

INTRODUCTION

Cyclooxygenase or also known as prostaglandin hormone synthases (COX-1 and COX-2) are an enzyme that catalyze the conversion of arachidonic acid to prostaglandin H2(PGH2), the common biosynthetic predecessor to prostaglandins and thromboxane. These bioactive lipids intercede numerous physiological and pathophysiological effects including fever, inflammation, pain, hemostasis, regulation of renal function and maintenance of mucosal integrity of the gastrointestinal tract. The pharmalogical effects of non-steroidal anti-inflammatory drugs (NSAIDs) came from the inhibition of COX enzymes. The two isoforms of COX encoded by genes, known as COX-1 which is precise in most tissues and is requisite for the production of PGs, which is involved in the housekeeping functions throughout the body. COX-2 which is an inducible enzyme, stimulated in a variety of cells in response to cytokines, mitogens and endotoxins. The two isoforms allocate high degree of amino acid sequence and structural homology. In the discovery of COX-2 in early 1990s and differences in its expression profile from COX-1 led to the hypothesis that specific inhibiton of COX-2 would be anti-inflammatory and analgesic but would lack the gastric toxicity associated with NSAIDs. It indicates that the anti-inflammatory effect of NSAIDs is due to the inhibition of COX-2 while ulcerogenic side effects arise from inhibition of COX-1. The severe gastrointestinal toxicity is due to their non-selective inhibition of COX-1 and COX-2.

CYCLOOXYGENASE

The Structure: COX and its form COX-1 and COX-2

The isoforms of COX (COX-1 and COX-2) are homodimers with molecular mass of approximately 70kDa per monomer (Fig 1). The tertiary and quaternary structures of the two enzymes are essentially identical. Each of the subunit is composed of three...