Arachidonate 15-lipoxygenase (ALOX15) (ALOX15)

Arachidonate 15-lipoxygenase (ALOX15) is a non-heme iron-containing enzyme that serves as the primary catalyst for the production of Protectins, a class of specialized pro-resolving mediators (SPMs) derived from docosahexaenoic acid (DHA) [4, 6, 9]. ALOX15 initiates the biosynthetic pathway by oxygenating DHA at the C-17 position to form 17S-hydroxydocosahexaenoic acid (17S-HpDHA), which is then converted into bioactive molecules like Protectin D1 (PD1) [6, 10]. These mediators are essential for the active resolution of inflammation, functioning to limit further neutrophil recruitment and stimulate the clearance of apoptotic cells by macrophages (efferocytosis) [1, 5]. Dysregulation of protectin production is implicated in the pathophysiology of chronic inflammatory and neurodegenerative diseases, including asthma, rheumatoid arthritis, and Alzheimer's disease, where the mediator is often referred to as Neuroprotectin D1 (NPD1) [3, 9]. Pharmacological modulation of this pathway involves the administration of DHA or omega-3 supplements to increase substrate availability for protectin synthesis [11, 12]. Additionally, aspirin can influence this process by acetylating COX-2, leading to the formation of aspirin-triggered protectin epimers (AT-PD1) that provide potent anti-inflammatory and tissue-protective effects [6, 10].

Other names

15-Lipoxygenase-115-LOX-115-LOXLOG15Arachidonate 15-lipoxygenase type I

Docosahexaenoic acid (DHA) serves as the primary substrate for ALOX15, which catalyzes its oxygenation to form the 17-hydroperoxy intermediate required for protectin synthesis. Aspirin modifies this pathway by acetylating COX-2, which then produces 17R-HpDHA that is converted by ALOX15 into potent aspirin-triggered protectin epimers.