Arachidonic acid metabolism in health and disease

Abstract

Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies

“…A large number of reporter metabolites were involved in arachidonic acid- and leukotriene-related metabolites. Arachidonic acid is an essential fatty acid, a major constituent of cell membrane phospholipids and precursor of bioactive lipids including leukotriene B4 (LTB4) leukotriene C4 (LTC4), leukotriene D4 (LTD4), leukotriene E4 (LTE4), epoxyeicosatrienoic acid, and hydroxyeicosatetraenoic acid . Since SARS-CoV-2 induces disturbances in leukotriene and arachidonic acid metabolisms, targeting them was offered as novel strategies to control the overall balance of their metabolites in patients with COVID-19. , Linoleic acid is the main source of essential n -6 polyunsaturated fatty acids, including arachidonic acid.…”

Long-Term Consumption of Purified Water Altered Amino Acid, Fatty Acid and Energy Metabolism in Livers of Rats

“…The abnormal metabolism of AA is closely related to the occurrence and development of many diseases, such as cardiovascular disease, inflammatory bowel disease, and asthma. Low AA levels affect sleep, elevate blood lipids, and cause fetal brain dysplasia [49]. DGLA has anti-inflammatory and antiproliferative properties [47].…”

Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention

“…More importantly, analysis of lipid metabolism in human polyps and tumor tissues may provide better insight into metabolic disturbances that contribute to carcinogenesis and provide new therapeutic strategies for identification, prevention, and therapy of this disease. Upregulation of the AA pathway occurs early in hyperplasia ( 90 , 91 ) and can activate tumor-related gene expression and signaling pathways ( 97 ). This pathway is targeted by non-steroidal anti-inflammatory drugs (NSAIDs), a common preventative treatment for FAP patients.…”