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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
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| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.363 |
| _version_ | 1797659181010911232 |
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| author | Yiran Zhang Yingxiang Liu Jin Sun Wei Zhang Zheng Guo Qiong Ma |
| author_facet | Yiran Zhang Yingxiang Liu Jin Sun Wei Zhang Zheng Guo Qiong Ma |
| author_sort | Yiran Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:10:08Z |
| format | Article |
| id | doaj.art-6179293b71194aba9dbd546ffa61692d |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-11T18:10:08Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-6179293b71194aba9dbd546ffa61692d2023-10-16T15:20:40ZengWileyMedComm2688-26632023-10-0145n/an/a10.1002/mco2.363Arachidonic acid metabolism in health and diseaseYiran Zhang0Yingxiang Liu1Jin Sun2Wei Zhang3Zheng Guo4Qiong Ma5Department of Orthopedic Surgery Orthopedic Oncology Institute The Second Affiliated Hospital of Air Force Medical University Xi'an ChinaDepartment of Orthopedic Surgery Orthopedic Oncology Institute The Second Affiliated Hospital of Air Force Medical University Xi'an ChinaDepartment of Orthopedic Surgery Orthopedic Oncology Institute The Second Affiliated Hospital of Air Force Medical University Xi'an ChinaDepartment of Pathology The Second Affiliated Hospital of Air Force Medical University Xi'an ChinaDepartment of Orthopedic Surgery Orthopedic Oncology Institute The Second Affiliated Hospital of Air Force Medical University Xi'an ChinaDepartment of Orthopedic Surgery Orthopedic Oncology Institute The Second Affiliated Hospital of Air Force Medical University Xi'an ChinaAbstract 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.https://doi.org/10.1002/mco2.363arachidonic acidbioactive lipid metabolitesorgan homeostasistargeted therapy |
| spellingShingle | Yiran Zhang Yingxiang Liu Jin Sun Wei Zhang Zheng Guo Qiong Ma Arachidonic acid metabolism in health and disease MedComm arachidonic acid bioactive lipid metabolites organ homeostasis targeted therapy |
| title | Arachidonic acid metabolism in health and disease |
| title_full | Arachidonic acid metabolism in health and disease |
| title_fullStr | Arachidonic acid metabolism in health and disease |
| title_full_unstemmed | Arachidonic acid metabolism in health and disease |
| title_short | Arachidonic acid metabolism in health and disease |
| title_sort | arachidonic acid metabolism in health and disease |
| topic | arachidonic acid bioactive lipid metabolites organ homeostasis targeted therapy |
| url | https://doi.org/10.1002/mco2.363 |
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