Phosphatidic acid is a phospholipid and an intermediate in glycerolipid biosynthesis. It is a transient intermediate in the synthesis of various phospholipid species that is synthesized de novo in cells via multiple routes, including the glycerol-3 phosphate and dihydroxyacetone phosphate pathways, enzymatic conversion of phosphatidylcholine by phospholipase D, and acetylation of lysophosphatidic acid by lysoPA-acyltransferase, among others. It has roles in shaping cellular membranes, cellular signaling, vesicle fission and fusion, as well as mitochondrial division and fusion. It stimulates respiratory burst in neutrophils independent of diacylglycerol and activates monoacylglycerol acyltransferase, phospholipase C (PLC), Ras, and phosphatidylinositol 4-phosphate (PIP4) kinase in several cell lines. Phosphatidic acids (egg) is a mixture of phosphatidic acids isolated from chicken egg with fatty acids of variable chain lengths.
Cyclic Phosphatidic Acids (cPAs) are naturally occurring lysophosphatidic acid (LPA) analogs, characterized by a 5-membered ring formed between the sn-2 hydroxy group and the sn-3 phosphate. Carba-derivatives of cPA (ccPA) modify the sn-2 (2-ccPA) or sn-3 (3-ccPA) linkage, hindering the conversion of cPA into LPA. Oleoyl 3-Carbacyclic Phosphatidic Acid (3-ccPA 18:1) incorporates the 18:1 fatty acid oleate at the sn-1 position on the glycerol backbone, acting as a cyclic LPA analog. This compound, at a concentration of 25 μM, blocks MM1 cells' transcellular migration through mesothelial cell monolayers induced by fetal bovine serum (by 90.1%) or LPA (by 99.9%), without impeding cell proliferation. Additionally, 3-ccPA 18:1, in the 0.1-1.0 μM range, notably suppresses autotaxin, which plays a vital role in various cancer cell behaviors including survival, growth, migration, invasion, and metastasis.
1-Palmitoyl-2-oleoyl-sn-glycero-3-PA (1,2-POPA) is a phospholipid featuring a palmitic acid (16:0) chain that is saturated and an oleic acid (18:1) chain that is monounsaturated, positioned at the sn-1 and sn-2 locations, respectively. This compound is utilized in creating micelles, liposomes, and various artificial membrane forms.
1-Arachidonoyl lysophosphatidic acid is a phospholipid containing arachidonic acid at the sn-1 position. It has been found in rat brain as 37% of the arachidonic acid-containing lysophosphatidic acid (LPA) species and is a precursor to 1-arachidonoyl glycerol . 1-Arachidonoyl lysophosphatidic acid binds to the LPA2/EDG4 receptor with an EC50 value of approximately 10 nM. It prevents TNF-α and IL-6 secretion in wild-type but not Lpa2-/- dendritic cells stimulated by LPS. It also decreases differentiation of HT-29 human colon carcinoma cells to goblet cells in the presence of sodium butyrate.
1-Palmitoyl lysophosphatidic acid (1-Palmitoyl LPA) is a LPA analog containing palmitic acid at the sn-1 position. LPA binds to one of five different G protein-coupled receptors (GPCRs) to mediate a variety of biological responses including cell proliferation, smooth muscle contraction, platelet aggregation, neurite retraction, and cell motility. In addition to playing a role in the aforementioned biological responses, 1-palmitoyl LPA enhances the action of β-lactam antibiotics (ampicillin, piperacillin, and ceftazidime) on various strains of Pseudomonas aeruginosa, a pathogen associated with pulmonary disease and pneumonia, via binding both Ca2+ and Mg2+.
1-Octadecyl lysophosphatidic acid (1-octadecyl LPA) is a LPA analog containing stearic acid at the sn-1 position. LPA binds to one of five different G protein linked receptors to mediate a variety of biological responses including cell proliferation, smooth muscle contraction, platelet aggregation, neurite retraction, and cell motility. Alkyl ether-linked LPA derivatives have a higher platelet aggregating activity than the acyl derivatives, most likely stemming from an alkyl-specific LPA receptor. For example, 1-octadecyl LPA has a platelet aggregating EC50 value of 9 nM versus 1-octadecanoyl LPA which has an EC50 value of 177 nM.
Diacylglycerols (DAG) are generated through the hydrolysis of membrane phospholipids and function as lipid second messengers by activating protein kinase C (PKC) and modulating cell growth and apoptosis. Additionally, they act as precursors for DAG kinases in the synthesis of phosphatidic acid, a crucial lipid messenger. The compound 1-NBD-decanoyl-2-decanoyl-sn-glycerol incorporates a nitrobenzoxadiazole (NBD) fluorophore at the ω-end of its terminal decanoyl chain, using the structure of 1,2-didecanoyl-sn-glycerol as a model for diacylglycerol. This molecule is expected to exhibit excitation and emission peaks at roughly 470/541 nm, paralleling those of various NBD-labeled phospholipids. Fluorescently labeled lipids, such as this, are instrumental in exploring their interactions with proteins, their uptake by cells and liposomes, and in developing assays for lipid metabolism research.
1,2-Dilinoleoyl-sn-glycerol is a diacylglycerol (DAG) with linoleic acid (18:2) side chains attached at both the sn-1 and sn-2 positions. It has been found as a component of phosphatidic acid in rat liver mitochondria and in spinach chloroplast membranes. 1,2-Dilinoleoyl-sn-glycerol is upregulated in some pregnant women and has been used as a biomarker to predict later preeclampsia in early pregnancy.
Cochlioquinone A is an inhibitor of diacylglycerol kinase (DGK) and diacylglycerol acyltransferase (DGAT). It has been shown to reduce the concentration of phosphatidic acid in T cell lymphoma and has also been shown to compete with macrophage inflammatory protein-1α for binding to human CCR5 chemokine receptors.