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.

中文翻译：

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健康和疾病中的花生四烯酸代谢。


花生四烯酸 (AA) 是一种 n-6 必需脂肪酸，是哺乳动物细胞的主要成分，可由磷脂酶 A2 释放。越来越多的证据表明，AA 起着重要的生化作用，因为它是类二十烷酸生物活性脂质代谢物的直接前体，例如前列腺素、白三烯和环氧二十碳三烯酸，这些代谢物通过三种不同的酶代谢途径获得：环氧合酶途径、脂氧合酶途径和细胞色素 P450 途径。 AA代谢不仅涉及细胞分化、组织发育和器官功能，还参与肝纤维化、神经退行性变、肥胖、糖尿病和癌症等疾病的进展。这些类二十烷酸通常被认为是促炎分子，因为它们可以引发氧化应激并刺激免疫反应。因此，干预AA代谢途径是临床治疗炎症相关疾病的有效方法。目前，针对 AA 代谢途径相关酶的抑制剂是药物发现的一个重要领域。此外，AA代谢抑制剂联合化疗和免疫治疗的临床研究也取得了许多进展。在此，我们回顾一下AA的发现，并重点关注AA代谢与健康和疾病的关系。此外，还总结了针对 AA 代谢的抑制剂，并讨论了潜在的临床应用。