Acetyl-CoA Carboxylases and Diseases.
Acetyl-CoA Carboxylases and Diseases.
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乙酰辅酶A羧化酶和疾病
DOI：
10.3389/fonc.2022.836058
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发表时间：
2022
影响因子：
4.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Wang Y;Yu W;Li S;Guo D;He J;Wang Y
乙酰辅酶A羧化酶（ACCs）是催化乙酰辅酶A羧化以产生丙二酰辅酶A的酶。在哺乳动物中，ACC 1和ACC 2是ACC的两个成员。ACC 1定位于胞质溶胶中，并作为从头脂肪酸合成途径中的第一个和限速酶。ACC 2定位于线粒体外膜，产生丙二酰辅酶A，调节肉毒碱棕榈酰转移酶1（CPT 1）的活性，参与脂肪酸的β-氧化。脂肪酸的合成是无数生理和病理条件的核心。ACC 1是哺乳动物ACC的主要成员，大量文献报道了ACC 1在多种疾病中的作用，如癌症、糖尿病、肥胖症等。此外，乙酰辅酶A和丙二酰辅酶A分别是蛋白质乙酰化和丙二酰化的辅因子，因此ACC 1对乙酰辅酶A和丙二酰辅酶A的操纵也会显着影响蛋白质翻译后修饰的谱，导致哺乳动物细胞生物学过程的交替。本文就ACCs的结构特征、调控机制及其在疾病中的作用等方面进行综述。ACC 1已成为一个很有前途的疾病治疗靶点，因此，ACC 1的特异性抑制剂用于疾病治疗也进行了讨论。
Acetyl-CoA carboxylases (ACCs) are enzymes that catalyze the carboxylation of acetyl-CoA to produce malonyl-CoA. In mammals, ACC1 and ACC2 are two members of ACCs. ACC1 localizes in the cytosol and acts as the first and rate-limiting enzyme in the de novo fatty acid synthesis pathway. ACC2 localizes on the outer membrane of mitochondria and produces malonyl-CoA to regulate the activity of carnitine palmitoyltransferase 1 (CPT1) that involves in the β-oxidation of fatty acid. Fatty acid synthesis is central in a myriad of physiological and pathological conditions. ACC1 is the major member of ACCs in mammalian, mountains of documents record the roles of ACC1 in various diseases, such as cancer, diabetes, obesity. Besides, acetyl-CoA and malonyl-CoA are cofactors in protein acetylation and malonylation, respectively, so that the manipulation of acetyl-CoA and malonyl-CoA by ACC1 can also markedly influence the profile of protein post-translational modifications, resulting in alternated biological processes in mammalian cells. In the review, we summarize our understandings of ACCs, including their structural features, regulatory mechanisms, and roles in diseases. ACC1 has emerged as a promising target for diseases treatment, so that the specific inhibitors of ACC1 for diseases treatment are also discussed.