Lipoygenases are enzymes that catalyze the oxidation of polyunsaturated fatty acids, playing diverse roles in signaling, structural changes, and lipid metabolism. They are found in plants, fungi, and animals, but not in most bacteria or yeast. The diversity of lipoygenase expression is highlighted, with different enzymes having distinct catalytic properties. For example, some tightly control reactions with molecular oxygen, while others produce mixed products and release free radicals. The phylogenetic tree separates plant and animal enzymes into subgroups, with sequence identity varying between species. Nomenclature is based on substrate specificity, with examples like 12-LOX and 15-LOX. Lipoygenases produce signaling molecules such as leukotrienes and HETEs, which have fast and slow actions, affecting cell surface receptors and long-term cellular processes. They also induce structural changes in membranes through lipid peroxidation, which is important in processes like red cell maturation and atherosclerosis. Gene knockout studies show that lipoygenases may not have obvious developmental issues, but their roles may become apparent under physiological or pathological stress. Some lipoygenases produce mixed products, while others catalyze the formation of a single product. The enzyme structure includes a non-heme iron center, and crystal structures reveal details about substrate access and catalysis. The acquisition of substrates is influenced by membrane interactions and carrier proteins. In mammals, 5-LOX interacts with FLAP to facilitate leukotriene biosynthesis. The discovery of novel enzymes, such as manganese lipoxygenases and R-lipoxygenases, provides new insights into catalytic mechanisms and stereospecificity. Overall, lipoygenases are essential in various biological processes, and their functions are complex and multifaceted.Lipoygenases are enzymes that catalyze the oxidation of polyunsaturated fatty acids, playing diverse roles in signaling, structural changes, and lipid metabolism. They are found in plants, fungi, and animals, but not in most bacteria or yeast. The diversity of lipoygenase expression is highlighted, with different enzymes having distinct catalytic properties. For example, some tightly control reactions with molecular oxygen, while others produce mixed products and release free radicals. The phylogenetic tree separates plant and animal enzymes into subgroups, with sequence identity varying between species. Nomenclature is based on substrate specificity, with examples like 12-LOX and 15-LOX. Lipoygenases produce signaling molecules such as leukotrienes and HETEs, which have fast and slow actions, affecting cell surface receptors and long-term cellular processes. They also induce structural changes in membranes through lipid peroxidation, which is important in processes like red cell maturation and atherosclerosis. Gene knockout studies show that lipoygenases may not have obvious developmental issues, but their roles may become apparent under physiological or pathological stress. Some lipoygenases produce mixed products, while others catalyze the formation of a single product. The enzyme structure includes a non-heme iron center, and crystal structures reveal details about substrate access and catalysis. The acquisition of substrates is influenced by membrane interactions and carrier proteins. In mammals, 5-LOX interacts with FLAP to facilitate leukotriene biosynthesis. The discovery of novel enzymes, such as manganese lipoxygenases and R-lipoxygenases, provides new insights into catalytic mechanisms and stereospecificity. Overall, lipoygenases are essential in various biological processes, and their functions are complex and multifaceted.