title: Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism.
abstract: 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.
authors: Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors: Caleb C
authors: CC
authors: Lord
authors: Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors: Gwynneth
authors: G
authors: Thomas
authors: Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors: J Mark
authors: JM
authors: Brown
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002265:Carboxylic Ester Hydrolases