Yang Liu, Liao Zhe-Zhen, Ran Li, Xiao Xin-Hua
Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Front Oncol. 2025 May 1;15:1564419. doi: 10.3389/fonc.2025.1564419. eCollection 2025.
Arylacetamide deacetylase (AADAC), a microsomal serine esterase belonging to the polygenic hydrolase family, is predominantly localized in the liver and intestine. It plays a significant role in drug metabolism, lipid metabolism, and the pathogenesis of various diseases. In the context of drug metabolism, AADAC is vital for ensuring the safety of ester-based drugs. Its substrate specificity for short-chain acyl groups, along with genetic polymorphisms among individuals and species, influences drug-related processes. Regarding lipid metabolism, The lipase activity of AADAC is involved in the hydrolysis of cholesterol and triglycerides, lipid mobilization, and the assembly of lipoproteins. The expression of AADAC is regulated by multiple factors. It is associated with metabolic disorders; for instance, its decreased expression in the liver during obesity may impact triglyceride metabolism, and it may also have an indirect role in diabetes. In cardiovascular diseases, AADAC holds potential as a diagnostic marker. Its role in cancer is heterogeneous, being downregulated in certain cancers while upregulated in others, such as pancreatic and ovarian cancers, where it acts to inhibit cancer progression. Within the nervous system, AADAC may influence neurotransmitter regulation and drug metabolism. Currently, research on AADAC agonists is limited, and the development of inhibitors presents challenges, underscoring the necessity for further investigation in this area.
芳基乙酰胺脱乙酰酶（AADAC）是一种属于多基因水解酶家族的微粒体丝氨酸酯酶，主要定位于肝脏和肠道。它在药物代谢、脂质代谢以及各种疾病的发病机制中发挥着重要作用。在药物代谢方面，AADAC对于确保酯类药物的安全性至关重要。其对短链酰基的底物特异性，以及个体和物种之间的基因多态性，影响着与药物相关的过程。在脂质代谢方面，AADAC的脂肪酶活性参与胆固醇和甘油三酯的水解、脂质动员以及脂蛋白的组装。AADAC的表达受多种因素调节。它与代谢紊乱有关；例如，肥胖期间肝脏中其表达降低可能影响甘油三酯代谢，并且它在糖尿病中可能也具有间接作用。在心血管疾病中，AADAC有望作为一种诊断标志物。它在癌症中的作用具有异质性，在某些癌症中表达下调，而在其他癌症如胰腺癌和卵巢癌中表达上调，在这些癌症中它起到抑制癌症进展的作用。在神经系统中，AADAC可能影响神经递质调节和药物代谢。目前，关于AADAC激动剂的研究有限，抑制剂的开发也面临挑战，这凸显了该领域进一步研究的必要性。
