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Prostaglandin G/H synthase 1 Prostaglandin G/H synthase 1 Prostaglandin G/H synthase 2 Arachidonate 5-lipoxygenase Solute carrier organic anion transporter family member 1B1 Solute carrier organic anion transporter family member 1B3 Solute carrier organic anion transporter family member 2B1 Prostaglandin E synthase Prostacyclin synthase Thromboxane-A synthase Cytosolic phospholipase A2 NADPH azoreductase Mesalazine Mesalazine Sulfasalazine Sulfasalazine Prostaglandin H2 Prostaglandin E2 Prostaglandin I2 Thromboxane A2 Arachidonic acid O2 Prostaglandin G2 H2O Leukotriene A4 Mesalazine Sulfapyridine Heme Heme Fe3+ Calcium Glutathione Heme Phospholipids Acceptor Reduced acceptor Prostaglandin G/H synthase 2 Heme Heme Heme Calcium NADPH Endoplasmic Reticulum Cytosol Extracellular space Mesalazine inhibits COX-1 (prostaglandin G/H synthase 1) and COX-2 (prostaglandin G/H synthase 2) on the endoplasmic reticulum membrane, preventing the conversion of arachidonic acid into PGH2. Prostaglandin H2 synthesis is reduced COX-1 synthesizes prostaglandins necessary for normal gastrointestinal and renal function. COX-2 is responsible for prostaglandin synthesis during tissue injury and inflammation. Inhibition of COX-2 provides anti-inflammatory activity. Prostaglandin E2 is responsible for inflammation and pain by activating immune cells and stimulating pain fibres. Lower concentrations of prostaglandin E2 lowers inflammatory and pain response, hence an analgesic effect is seen. Decreasing PGE2 in the central nervous system also has an antipyretic effect. Epithelial cell Intestine The inhibition of the arachidonate 5-lipoxygenase enzyme results in the decrease of the biosynnthesis of leukotriene. This decreases the inflammation. Bacteria in the large intestine Both metabolites are active but most of the sulfapyridine is absorbed by the intestine while most mesalazine is not and will stay in the colon.
Endoplasmic Reticulum PTGS1 PTGS1 PTGS2 ALOX5 SLCO1B1 SLCO1B3 SLCO2B1 PTGES PTGIS TBXAS1 PLA2G4A azr Mesalazine Mesalazine Sulfasalazine Sulfasalazine Prostaglandin H2 Prostaglandin E2 Prostaglandin I2 Thromboxane A2 Arachidonic acid Oxygen Prostaglandin G2 Water Leukotriene A4 Mesalazine Sulfapyridine Phospholipids Acceptor Reduced acceptor PTGS2