PMC

Main enzymes and G protein-coupled receptors in the cyclooxygenase pathway. Arachidonic acid is converted to PGG₂ by cyclooxygenase 1 or 2 and PGG₂ then undergoes conversion to PGH₂ through the peroxidase activity of COX. Several isomerases convert PGH₂ to other 2-series prostaglandins, prostacyclins or thromboxanes, which act in part by binding to specific prostanoid receptors (green). EPA is thought to serve as a substrate for the same set of enzymes to generate three-series eicosanoids (PGH₃, PGE₃, etc.). Some prostanoids have also been shown to bind to PPARs (not shown). Official protein symbols are shown in red for enzymes and in green for receptors, with common abbreviations in parenthesis. PTGS1–2 prostaglandin-endoperoxide synthase 1–2, PTGDS PGD₂ synthase (brain), HPGDS hematopoietic PGD synthase, PTGES1–3 PGE synthase 1–3, PTGIS PGI₂ (prostacyclin) synthase, TBXAS1 TXA synthase 1, PTGDR PGD₂ receptor, PTGER1–4 PGE receptor 1–4 (subtype EP1–4), PTGFR PG F receptor, PTGIR PGI₂ (prostacyclin) receptor, TBXA2R TXA₂ receptor

Conversion of ω6 and ω3 series PUFA by metabolic enzymes and interaction with de novo fatty acid synthesis. The main dietary ω6 and ω3 PUFA (LA, 18:2 n-6 and αLNA, 18:3 n-3) undergo a series of desaturation (FADS2, FADS1) and elongation (ELOVL5, KAR, HACD, TECR) steps converting them to AA and EPA, respectively. The in vitro conversion rates of these enzymatic steps are indicated as percent of product formed from 150 nmol substrate incubated with 5 mg of rat liver microsomal protein for 3 min []. Long-chain PUFA are converted to prostaglandins (PG) and thromboxanes (TX) by cyclooxygenases (COX1–2) or to leukotrienes (LT) and hydroxyeicosatetraenoic acids (HETE) by lipoxygenases (LOX). EPA can be further elongated and desaturated to DHA in a pathway involving β-oxidation in the peroxisome. In the presence of aspirin, COX2 metabolizes EPA and DHA to resolvins. The various products play important roles in inflammation, cell proliferation and apoptosis, and angiogenesis. In the de novo lipid synthesis pathway, acetyl-CoA and malonyl-CoA can be interconverted by acetyl-CoA carboxylase (ACC1) and malonyl-CoA decarboxylase (MLYCD). Acetyl-CoA and malonyl-CoA are used as substrates by fatty acid synthase (FASN) to generate long-chain saturated fatty acids, which can be elongated further (ELOVL6) or desaturated (SCD) to form monounsaturated fatty acids. Malonyl-CoA is also required for elongation of ω6 and ω3 PUFA