Eicosanoid-producing enzymes

Eicosanoid-producing enzymes represent a broad class of enzymes that catalyze the conversion of polyunsaturated fatty acids, primarily arachidonic acid, into potent lipid signaling molecules known as eicosanoids [1, 2]. This group includes three major enzymatic pathways: the cyclooxygenase (COX) pathway, which produces prostaglandins and thromboxanes; the lipoxygenase (LOX) pathway, which generates leukotrienes and lipoxins; and the cytochrome P450 (CYP) pathway, which produces epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) [1, 3]. These mediators are critical regulators of inflammation, pain, fever, vascular tone, and platelet function [1, 4]. Dysregulation of eicosanoid production is implicated in a wide range of pathologies, including chronic inflammatory diseases like rheumatoid arthritis, respiratory conditions like asthma, cardiovascular diseases, and various cancers [2, 5]. Pharmacological intervention typically involves the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit COX enzymes or specific inhibitors like zileuton to target 5-LOX [4, 6]. While highly effective for managing pain and inflammation, targeting these enzymes can lead to significant side effects, such as gastrointestinal bleeding or increased cardiovascular risk, due to the disruption of homeostatic lipid signaling [1, 6]. [1] https://www.ncbi.nlm.nih.gov/books/NBK542314/ [2] https://www.nature.com/articles/nrd.2017.115 [3] https://www.jlr.org/article/S0022-2275(20)30114-1/fulltext [4] https://pubmed.ncbi.nlm.nih.gov/15556670/ [5] https://www.atsjournals.org/doi/full/10.1164/rccm.200204-317PP [6] https://www.nejm.org/doi/full/10.1056/NEJMra052706

Other names

Arachidonate metabolic enzymesEicosanoid biosynthetic enzymesProstanoid and leukotriene synthasesArachidonic acid metabolizing enzymes

Inhibition of specific enzymes within the eicosanoid biosynthetic pathways (e.g., COX-1, COX-2, 5-LOX) to reduce the production of pro-inflammatory or pro-thrombotic lipid mediators [1, 4, 6].