Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism.
Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism.
复制标题
DOI：
10.1016/j.bbalip.2013.01.002
复制
发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Brown JM
中科院分区：
文献类型：
--
作者：
Lord CC;Thomas G;Brown JM
脂质代谢失调是许多慢性疾病如肥胖、糖尿病、心血管疾病和癌症的基础。因此，了解控制脂质合成和降解的酶机制对于成功发现这些人类疾病的药物至关重要。编码α/β水解酶折叠结构域（ABHD）蛋白的基因几乎存在于所有已报道的基因组中，这些蛋白共有的保守结构基序预测了在脂质合成和降解中的共同作用。然而，这些脂质代谢酶的生理底物和产物及其在代谢途径中更广泛的作用在很大程度上仍然是未知的。最近，ABHD蛋白家族的几个成员的突变与遗传性先天性脂质代谢缺陷有关。此外，在细胞和动物模型中的研究已经揭示了ABHD蛋白在脂质代谢、脂质信号转导和代谢疾病中的重要作用。这篇评论的目的是提供一个全面的总结，围绕目前的知识状态有关哺乳动物ABHD蛋白家族成员。特别是，我们将讨论ABHD蛋白如何非常适合在脂质代谢和信号传导的界面上发挥作用。虽然，目前关于哺乳动物ABHD蛋白质的知识状态仍处于起步阶段，本次审查突出了ABHD酶作为针对代谢疾病的新疗法的有吸引力的目标的潜力。
Dysregulation of lipid metabolism underlies many chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Therefore, understanding enzymatic mechanisms controlling lipid synthesis and degradation is imperative for successful drug discovery for these human diseases. Genes encoding α/β hydrolase fold domain (ABHD) proteins are present in virtually all reported genomes, and conserved structural motifs shared by these proteins predict common roles in lipid synthesis and degradation. However, the physiological substrates and products for these lipid metabolizing enzymes and their broader role in metabolic pathways remain largely uncharacterized. Recently, mutations in several members of the ABHD protein family have been implicated in inherited inborn errors of lipid metabolism. Furthermore, studies in cell and animal models have revealed important roles for ABHD proteins in lipid metabolism, lipid signal transduction, and metabolic disease. The purpose of this review is to provide a comprehensive summary surrounding the current state of knowledge regarding mammalian ABHD protein family members. In particular, we will discuss how ABHD proteins are ideally suited to act at the interface of lipid metabolism and signal transduction. Although, the current state of knowledge regarding mammalian ABHD proteins is still in its infancy, this review highlights the potential for the ABHD enzymes as being attractive targets for novel therapies targeting metabolic disease.