phosphatidic acid metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving phosphatidic acid, any derivative of glycerol phosphate in which both the remaining hydroxyl groups of the glycerol moiety are esterified with fatty acids. [ISBN:0198506732]

Phosphatidic acid (PA) is a central intermediate in lipid metabolism, playing a crucial role in various cellular processes. Its metabolism is tightly regulated and involves a complex interplay of enzymes. The process begins with the synthesis of PA from diacylglycerol (DAG) by the enzyme diacylglycerol kinase (DGK). DGK isoforms are differentially expressed in various tissues and have distinct regulatory mechanisms.

PA can also be generated through the hydrolysis of phosphoinositides by phospholipases C and D, or by the dephosphorylation of phosphatidylinositol 4-phosphate (PIP) by phosphatidylinositol 4-phosphatase. These alternative pathways contribute to the dynamic regulation of PA levels in cells.

PA is a precursor for the synthesis of other important phospholipids, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Its conversion to these phospholipids is mediated by specific enzymes, such as CTP:phosphocholine cytidylyltransferase (CCT) and phosphatidylinositol synthase (PIS).

Beyond its role as a precursor for other lipids, PA itself exerts a range of cellular functions. It acts as a second messenger, modulating intracellular signaling pathways involved in cell growth, proliferation, and survival. PA activates various downstream signaling molecules, including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), and Ras.

PA also interacts with membrane proteins, influencing their activity and localization. For example, PA can bind to and activate certain ion channels, regulate the trafficking of proteins, and contribute to membrane organization.

In addition to its involvement in cellular signaling, PA plays a role in the formation of lipid droplets, which are organelles responsible for storing neutral lipids. PA can also be incorporated into the lipid bilayer, modulating membrane fluidity and curvature.

The metabolic fate of PA is determined by its conversion to other lipids or its degradation. PA can be dephosphorylated by lipid phosphatases, yielding DAG, or it can be converted to CDP-diacylglycerol (CDP-DAG), a precursor for the synthesis of cardiolipin and phosphatidylglycerol.

The metabolic process of phosphatidic acid is highly complex and tightly regulated, ensuring the proper balance of PA levels in cells. Dysregulation of PA metabolism has been implicated in various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. Understanding the intricate mechanisms governing PA metabolism is crucial for developing novel therapeutic strategies targeting these diseases.'
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Proteins (4)

Compounds (15)