ALOX - Arachidonate lipoxygenase | Elisa - Clia - Antibody - Protein

Background:

Arachidonate lipoxygenases (ALOX) are a family of enzymes that catalyze the dioxygenation of polyunsaturated fatty acids, particularly arachidonic acid, to produce bioactive lipid mediators known as leukotrienes and lipoxins. These enzymes play critical roles in inflammation, immune response, and various physiological processes. There are several members of the ALOX family, each with specific substrate preferences and tissue distributions.ALOX5,also known as 5-lipoxygenase (5-LOX), this enzyme is primarily involved in the synthesis of leukotrienes from arachidonic acid. Leukotrienes are potent lipid mediators that contribute to inflammation and allergic reactions.ALOX12 also called 12-lipoxygenase (12-LOX), acts on arachidonic acid to produce 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can further be converted into various bioactive lipid mediators, including lipoxins. ALOX15 also known as 15-lipoxygenase (15-LOX), this enzyme can act on both arachidonic acid and linoleic acid to produce 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 13-hydroperoxyoctadecadienoic acid (13-HPODE), respectively. ALOX15 is involved in inflammation, cell differentiation, and lipid metabolism

Protein Structure:

• Domains: ALOX enzymes typically have a conserved lipoxygenase domain responsible for their catalytic activity.
• Active Site: The active site contains a non-heme iron ion coordinated by conserved histidine residues. This iron is essential for the enzyme's ability to catalyze the dioxygenation of polyunsaturated fatty acids.
• Structural Features: The enzymes have a barrel-shaped structure, which accommodates the fatty acid substrate and positions it for oxidation.

Classification and Subtypes:

• ALOX5 (5-Lipoxygenase): Primarily converts arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which can be further metabolized to leukotrienes, important mediators in inflammation and allergic reactions.
• ALOX12 (12-Lipoxygenase): Catalyzes the formation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE), involved in platelet aggregation and vascular function.
• ALOX15 (15-Lipoxygenase): Produces 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which plays a role in the resolution of inflammation and cell differentiation.

Function and Biological Significance:

• Inflammation and Immunity: Lipoxygenase products, such as leukotrienes and hydroxyeicosatetraenoic acids (HETEs), are key regulators of inflammatory responses and immune cell function.
• Cell Signaling: ALOX enzymes generate lipid mediators that act as signaling molecules, influencing processes like cell proliferation, differentiation, and apoptosis.
• Homeostasis: By modulating the balance of lipid mediators, ALOX enzymes help maintain homeostasis in tissues, particularly in the cardiovascular and immune systems.

Interactions:

• Substrate Interaction: ALOX enzymes interact with polyunsaturated fatty acids, positioning them in the active site for oxygenation.
• Protein Partners: These enzymes interact with other proteins involved in lipid metabolism and signaling, such as phospholipases and cyclooxygenases, to coordinate the production of various lipid mediators.
• Cellular Interactions: ALOX enzymes are often part of larger signaling complexes and interact with receptors on cell surfaces to influence cellular responses.

Clinical Issues:

• Inflammatory Diseases: Dysregulation of ALOX activity is implicated in various inflammatory diseases, including asthma, rheumatoid arthritis, and inflammatory bowel disease. Overproduction of leukotrienes by ALOX5, for example, contributes to the pathophysiology of asthma.
• Cancer: Aberrant expression of ALOX enzymes has been linked to cancer. ALOX12 and ALOX15, in particular, have roles in tumor progression and metastasis by affecting cell proliferation and survival pathways.
• Cardiovascular Diseases: ALOX-derived lipid mediators are involved in the regulation of vascular function and platelet aggregation. Imbalances in these pathways can contribute to atherosclerosis and other cardiovascular conditions.

Summary:

Arachidonate lipoxygenases (ALOX) are vital enzymes in the metabolism of polyunsaturated fatty acids, producing lipid mediators that regulate inflammation, immunity, and cell signaling. Key members include ALOX5, ALOX12, and ALOX15, each with specific roles in generating bioactive lipids. These enzymes are integral to maintaining physiological homeostasis, but their dysregulation can lead to various diseases, including inflammatory disorders, cancer, and cardiovascular diseases. Understanding the functions and regulatory mechanisms of ALOX enzymes is crucial for developing therapeutic strategies targeting their activity in disease contexts.