Diacylglycerol acyltransferase 1 is activated by phosphatidate and inhibited by SnRK1-catalyzed phosphorylation

Phosphatidic acid (PA) has emerged as a new class of lipid mediators involved in diverse cellular functions in plants, animals, and microorganisms. Considerable progress has been made recently on the production, cellular function, and mode of action of PA in the cell. The cellular levels of PA undergo dynamic changes in response to developmental and environmental stimuli. The production of signaling PA is mediated by families of multiple enzymes that regulate the timing, location, amount, and molecular species of PA. A number of PA target proteins have been identified, which include proteins involved in phosphorylation and dephosphorylation of proteins and lipids, as well as in G protein regulation, vesicular trafficking, and metabolism. PA mediates cellular functions through different modes of action, such as membrane tethering, modulation of enzymatic activities, and/or structural effects on cell membranes. The regulatory processes in which PA has been implicated include signaling pathways in cell growth, proliferation, reproduction, and responses to hormones and biotic and abiotic stresses.

Triacylglycerol (TG) is a storage lipid which serves as an energy reservoir and a source of signalling molecules and substrates for membrane biogenesis. TG is essential for many physiological processes and its metabolism is widely conserved in nature. Acyl-CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the final step in the sn-glycerol-3-phosphate pathway leading to TG. DGAT activity resides mainly in two distinct membrane bound polypeptides, known as DGAT1 and DGAT2 which have been identified in numerous organisms. In addition, a few other enzymes also hold DGAT activity, including the DGAT-related acyl-CoA:monoacylglycerol acyltransferases (MGAT). Progress on understanding structure/function in DGATs has been limited by the lack of detailed three-dimensional structural information due to the hydrophobic properties of theses enzymes and difficulties associated with purification. This review examines several aspects of DGAT and MGAT genes and enzymes, including current knowledge on their gene structure, expression pattern, biochemical properties, membrane topology, functional motifs and subcellular localization. Recent progress in probing structural and functional aspects of DGAT1 and DGAT2, using a combination of molecular and biochemical techniques, is emphasized. Biotechnological applications involving DGAT enzymes ranging from obesity therapeutics to oilseed engineering are also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The CDP-choline pathway of phosphatidylcholine (PtdCho) biosynthesis was first described more than 50 years ago. Investigation of the CDP-choline pathway in yeast provides a basis for understanding the CDP-choline pathway in mammals. PtdCho is considered as an intermediate in a cycle of synthesis and degradation, and the activity of a CDP-choline cycle is linked to subcellular membrane lipid movement. The components of the mammalian CDP-choline pathway include choline transport, choline kinase, phosphocholine cytidylyltransferase, and choline phosphotransferase activities. The protein isoforms and biochemical mechanisms of regulation of the pathway enzymes are related to their cell- and tissue-specific functions. Regulated PtdCho turnover mediated by phospholipases or neuropathy target esterase participates in the mammalian CDP-choline cycle. Knockout mouse models define the biological functions of the CDP-choline cycle in mammalian cells and tissues. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. Copyright © 2012 Elsevier B.V. All rights reserved.