Structure And Expression Of Cox1 And Cox2

The cyclooxygenase enzyme system, also known as prostaglandin H synthetase (PGHS), is composed of two distinct isoenzymes, cyclooxy-genase-1 (COX-1) and cyclooxygenase-2 (COX-2). These enzymes form part of the prostaglandin synthetase complex of enzymes, which plays a key role in the conversion of arachidonic acid into prostaglandin G2 (PGG2). This molecule is subsequently transformed into individual prostaglandins by tissue-specific components of the synthetase complex, such as hydroperoxidase (Figure 1).

Both enzymes are both homodimeric, haem-containing, glycosylated proteins.

Although approximately 60% identical, studies of crystal structure have revealed COX-2 has a larger active site. This is consistent with what is termed "substrate promiscuity" of COX-2, a property which enables the enzyme to metabolise molecules structurally similar to prostaglandins, such as linoleic acid and anandamide (2, 3).

COX-1 and COX-2 are encoded by genes which are tightly regulated, and located on different chromosomes (4). The isoenzymes differ substantially in patterns of expression and biology.

The COX-1 gene is essentially a "housekeeping gene", expressed at a constant level throughout the cell cycle, and by almost all tissues. It has therefore been termed "the constitutive isoenzyme".

In contrast, the COX-2 gene is an "immediate to early gene" (5, 6).

COX-2 is induced rapidly in response to growth factors, tumour promoters, hormones, bacterial endotoxin, cytokines, and shear stress (7), and has a number of inducible enhancer elements. COX-2 is often termed "the inducible isoenzyme" (8), but this is an oversimplification, as the gene is expressed constitutively in brain, testes, and trachea (9-12).

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