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Chemical modulation of glycerolipid signaling and metabolic pathways
Authors:Sarah A. Scott  Thomas P. Mathews  Pavlina T. Ivanova  Craig W. Lindsley  H. Alex Brown
Affiliation:1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA;3. Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA;4. Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA;5. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37235, USA
Abstract:
Thirty years ago, glycerolipids captured the attention of biochemical researchers as novel cellular signaling entities. We now recognize that these biomolecules occupy signaling nodes critical to a number of physiological and pathological processes. Thus, glycerolipid-metabolizing enzymes present attractive targets for new therapies. A number of fields—ranging from neuroscience and cancer to diabetes and obesity—have elucidated the signaling properties of glycerolipids. The biochemical literature teems with newly emerging small molecule inhibitors capable of manipulating glycerolipid metabolism and signaling. This ever-expanding pool of chemical modulators appears daunting to those interested in exploiting glycerolipid-signaling pathways in their model system of choice. This review distills the current body of literature surrounding glycerolipid metabolism into a more approachable format, facilitating the application of small molecule inhibitors to novel systems. This article is part of a Special Issue entitled Tools to study lipid functions.
Keywords:PLC, phospholipase C   PLD, phospholipase D   PLA, phospholipase A   PtdBuOH, phosphatidylbutanol   PC, phosphatidylcholine   PA, phosphatidic acid   PG, phosphatidylglycerol   PE, phosphatidylethanolamine   PS, phosphatidylserine   LPC, lysophosphatidylcholine   LPA, lysophosphatidic acid   ATX, autotaxin   PIP2, phosphatidylinositol bisphosphate   DAG, diacylglycerol   AA, arachidonic acid   2-AG, 2-arachidonoylglycerol   FA, fatty acid   FFA, free fatty acid   DGK, diacylglycerol kinase   PI3K, phosphatidylinositol 3-kinase   MGLL, monoacylglycerol lipase   DAGL, diacylglycerol lipase   TAG, triacylglycerol   HSL, hormone-sensitive lipase   ATGL, adipose triacylglycerol lipase   CGI-58, comparative gene identification 58   ADHD5, α/β hydrolase domain-containing protein 5   LPAAT, lysophosphatidic acid acyltransferase   PNPLA, patatin-like phospholipase domain-containing proteins   GPAT, glycerol-3-phosphate acyltransferase   DGAT, diacylglycerol acyltransferase
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