Lord Caleb C, Thomas Gwynneth, Brown J Mark
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Biochim Biophys Acta. 2013 Apr;1831(4):792-802. doi: 10.1016/j.bbalip.2013.01.002. Epub 2013 Jan 14.
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.
脂质代谢失调是许多慢性疾病（如肥胖症、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促机制对于成功研发治疗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示着它们在脂质合成和降解中具有共同作用。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的更广泛作用在很大程度上仍未得到明确。最近，ABHD蛋白家族的几个成员中的突变已被认为与遗传性脂质代谢先天性缺陷有关。此外，细胞和动物模型研究揭示了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。本综述的目的是全面总结关于哺乳动物ABHD蛋白家族成员的当前知识状态。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转导的界面发挥作用。尽管目前关于哺乳动物ABHD蛋白的知识仍处于起步阶段，但本综述强调了ABHD酶作为针对代谢疾病的新型疗法的有吸引力靶点的潜力。
