Prostaglandin endoperoxide H synthases (PGHSs), also known as cyclooxygenases (COXs), are enzymes that catalyze the conversion of arachidonic acid and oxygen into PGH2, a key step in prostanoid biosynthesis. There are two isoforms, PGHS-1 (COX-1) and PGHS-2 (COX-2). PGHS-1 is constitutively expressed in most tissues and is involved in maintaining normal physiological functions, while PGHS-2 is inducible and is primarily involved in inflammatory responses. Both isoforms are important pharmacologically as targets of nonsteroidal anti-inflammatory drugs (NSAIDs), with PGHS-2 being the main target for anti-inflammatory effects. PGHS-2 is rapidly induced in response to various stimuli such as growth factors, tumor promoters, and cytokines, and is classified as an immediate early gene. Its expression is regulated by multiple signaling pathways, including those involving protein kinases A and C, tyrosine kinases, and bacterial endotoxin. PGHS-2 is also inhibited by anti-inflammatory steroids like cortisol and dexamethasone through both transcriptional and post-transcriptional mechanisms. PGHS-1 and PGHS-2 are homodimeric, heme-containing, glycosylated proteins with two catalytic sites. They are anchored to the lipid bilayer through amphipathic helices rather than transmembrane motifs. Both enzymes have similar catalytic turnover numbers and substrate affinities, but subtle differences exist in peroxide requirements and fatty acid substrate specificity. The catalytic mechanisms of both isoforms are largely similar, with the cyclooxygenase and peroxidase activities being physically and functionally separate. NSAIDs inhibit PGHS activity by competing with arachidonate for binding to the cyclooxygenase site, but have little effect on peroxidase activity. Aspirin, in particular, causes covalent modification and irreversible inhibition of PGHSs, which is why it has a long-lasting effect on platelet function. In contrast, other NSAIDs like ibuprofen act as reversible competitive inhibitors. PGHS-1 and PGHS-2 are encoded by separate genes located on different chromosomes. PGHS-1 is approximately 22 kilobase pairs long and lacks a TATA box, while PGHS-2 is 8 kilobase pairs long and contains 10 exons. The regulation of PGHS-1 expression is not well understood, while PGHS-2 expression is regulated through multiple signaling pathways. PGHS-1 and PGHS-2 are involved in different prostanoid biosynthetic systems. PGHS-1 is part of an ER system that produces prostanoids acting extracellularly, while PGHS-2 is involved in a nuclear system that produces prostanoids acting intracellularly.Prostaglandin endoperoxide H synthases (PGHSs), also known as cyclooxygenases (COXs), are enzymes that catalyze the conversion of arachidonic acid and oxygen into PGH2, a key step in prostanoid biosynthesis. There are two isoforms, PGHS-1 (COX-1) and PGHS-2 (COX-2). PGHS-1 is constitutively expressed in most tissues and is involved in maintaining normal physiological functions, while PGHS-2 is inducible and is primarily involved in inflammatory responses. Both isoforms are important pharmacologically as targets of nonsteroidal anti-inflammatory drugs (NSAIDs), with PGHS-2 being the main target for anti-inflammatory effects. PGHS-2 is rapidly induced in response to various stimuli such as growth factors, tumor promoters, and cytokines, and is classified as an immediate early gene. Its expression is regulated by multiple signaling pathways, including those involving protein kinases A and C, tyrosine kinases, and bacterial endotoxin. PGHS-2 is also inhibited by anti-inflammatory steroids like cortisol and dexamethasone through both transcriptional and post-transcriptional mechanisms. PGHS-1 and PGHS-2 are homodimeric, heme-containing, glycosylated proteins with two catalytic sites. They are anchored to the lipid bilayer through amphipathic helices rather than transmembrane motifs. Both enzymes have similar catalytic turnover numbers and substrate affinities, but subtle differences exist in peroxide requirements and fatty acid substrate specificity. The catalytic mechanisms of both isoforms are largely similar, with the cyclooxygenase and peroxidase activities being physically and functionally separate. NSAIDs inhibit PGHS activity by competing with arachidonate for binding to the cyclooxygenase site, but have little effect on peroxidase activity. Aspirin, in particular, causes covalent modification and irreversible inhibition of PGHSs, which is why it has a long-lasting effect on platelet function. In contrast, other NSAIDs like ibuprofen act as reversible competitive inhibitors. PGHS-1 and PGHS-2 are encoded by separate genes located on different chromosomes. PGHS-1 is approximately 22 kilobase pairs long and lacks a TATA box, while PGHS-2 is 8 kilobase pairs long and contains 10 exons. The regulation of PGHS-1 expression is not well understood, while PGHS-2 expression is regulated through multiple signaling pathways. PGHS-1 and PGHS-2 are involved in different prostanoid biosynthetic systems. PGHS-1 is part of an ER system that produces prostanoids acting extracellularly, while PGHS-2 is involved in a nuclear system that produces prostanoids acting intracellularly.