Exploring the Roles of Phosphatidic Acid in Lipid Metabolism and Lipidomics Research

Phosphatidic acid (PA) is a key intermediate in lipid metabolism and an important precursor for various lipid molecules, including phosphatidylinositol, phosphatidylcholine, and triacylglycerol. In recent years, there has been a growing interest in understanding the role of PA in lipid metabolism and signaling pathways, as well as its potential applications in lipidomics research.

Structure and Composition of Phosphatidic Acid

PA is a phospholipid molecule with a glycerol backbone, two fatty acid chains, and a phosphate group. Its structure and composition can vary depending on the types of fatty acid chains and head groups attached to the glycerol backbone. PA is synthesized via the enzymatic conversion of diacylglycerol (DAG) by DAG kinase, which phosphorylates the hydroxyl group on the sn-3 position of DAG to produce PA. PA can also be synthesized via the acylation of lysophosphatidic acid by lysophosphatidic acid acyltransferase.

Enzymatic routes for structural and signaling PA metabolism (Tanguy et al., 2019).

Phosphatidic Acid in Lipid Metabolism

PA plays a crucial role in lipid metabolism as a precursor for other important lipid molecules. For example, PA can be converted to phosphatidylinositol by the sequential addition of inositol phosphate groups. Phosphatidylinositol is an important signaling molecule involved in various cellular processes, including membrane trafficking, cell division, and apoptosis. PA can also be converted to phosphatidylcholine via the Kennedy pathway, which is the major pathway for phosphatidylcholine synthesis in most cells. Phosphatidylcholine is an important component of cell membranes and is involved in membrane fusion, lipid transport, and signaling.

PA can also be converted to triacylglycerol, which is the major form of energy storage in cells. The synthesis of triacylglycerol from PA involves the sequential addition of three fatty acids to the glycerol backbone, catalyzed by diacylglycerol acyltransferase. Triacylglycerol can be stored in lipid droplets or used as an energy source during times of energy deprivation.

Phosphatidic acid is a key precursor in lipid metabolism (Shin et al., 2011)

Phosphatidic Acid Lipidomics Research

Lipidomics is the comprehensive analysis of lipid molecules in cells, tissues, or organisms. It aims to identify and quantify lipid molecules and their functions in various biological processes. PA has emerged as an important target for lipidomics research due to its central role in lipid metabolism and signaling pathways.

A lipidomics approach to measure PA species in subcellular membrane fractions has been developed using high-performance liquid chromatography (HPLC) and mass spectrometry. This approach enables the identification and quantification of different PA species in various subcellular fractions, providing insights into their functions in cellular processes.

Experimental workflow of lipid mediators analysis using MRM (Sorgi et al., 2018)

Phosphatidic acid pathway and synthesis can also be studied using lipidomics approaches. For example, the synthesis of PA via the Kennedy pathway can be studied by measuring the levels of different intermediates in the pathway, such as CDP-choline and phosphatidylcholine. The levels of these intermediates can provide insights into the regulation of the pathway and its involvement in cellular processes.

Additionally, lipidomics approaches can be used to study the regulation of PA levels in response to various stimuli, such as growth factors, hormones, or stress. Changes in PA levels can indicate the activation or inhibition of signaling pathways, providing insights into the functions of PA in these pathways.

References

1. Tanguy, Emeline, et al. "Phosphatidic acid: from pleiotropic functions to neuronal pathology." Frontiers in cellular neuroscience 13 (2019): 2.
2. Shin, John JH, and Christopher JR Loewen. "Putting the pH into phosphatidic acid signaling." BMC biology 9 (2011): 1-11.
3. Sorgi, Carlos Artério, et al. "Comprehensive high-resolution multiple-reaction monitoring mass spectrometry for targeted eicosanoid assays." Scientific Data 5.1 (2018): 1-12.

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