Lysophosphatidic acid

Lysophosphatidic acid
Names
	Preferred IUPAC name (2R)-2-hydroxy-3-{[(9Z)-octadec-9-enoyl]oxy}propyl dihydrogen phosphate
	Other names LPA; 1-acyl-sn-glycerol 3-phosphate
Identifiers
CAS Number	22002-87-5 ;
3D model (JSmol)	Interactive image ;
ChEMBL	ChEMBL117021 ;
ChemSpider	4593722 ;
ECHA InfoCard	100.040.631
EC Number	244-710-0;
IUPHAR/BPS	2906 ;
MeSH	lysophosphatidic+acid
PubChem CID	5497152 ;
UNII	PG6M3969SG ;
CompTox Dashboard (EPA)	DTXSID5041061 ;
	InChI InChI=1S/C21H41O7P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-21(23)27-18-20(22)19-28-29(24,25)26/h9-10,20,22H,2-8,11-19H2,1H3,(H2,24,25,26)/b10-9- Key: WRGQSWVCFNIUNZ-KTKRTIGZSA-N;
	SMILES CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(=O)(O)O)O;
Properties
Chemical formula	C21H41O7P
Molar mass	436.52 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Last updated February 21, 2023

Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.^[1]^[2]^[3]^[4]

Function

LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (also known as EDG2, EDG4, and EDG7). Additional, newly identified LPA receptors include LPAR4 (P2RY9, GPR23), LPAR5 (GPR92) and LPAR6 (P2RY5, GPR87).

Clinical significance

Because of its ability to stimulate cell proliferation, aberrant LPA-signaling has been linked to cancer in numerous ways. Dysregulation of autotaxin or the LPA receptors can lead to hyperproliferation, which may contribute to oncogenesis and metastasis.^[5]

LPA may be the cause of pruritus (itching) in individuals with cholestatic (impaired bile flow) diseases.

GTPase activation

Downstream of LPA receptor activation, the small GTPase Rho can be activated, subsequently activating Rho kinase. This can lead to the formation of stress fibers and cell migration through the inhibition of myosin light-chain phosphatase.

Metabolism

There are a number of potential routes to its biosynthesis, but the most well-characterized is by the action of a lysophospholipase D called autotaxin, which removes the choline group from lysophosphatidylcholine.

Lysophosphatidic acid is also an intermediate in the synthesis of phosphatidic acid.

Related Research Articles

Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes. Two major classes are known: those for bacteria and eukaryotes and a separate family for archaea.

Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.

Phospholipase D (EC 3.1.4.4, lipophosphodiesterase II, lecithinase D, choline phosphatase, PLD; systematic name phosphatidylcholine phosphatidohydrolase) is an enzyme of the phospholipase superfamily that catalyses the following reaction

The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling. In humans, there are eleven LPL receptors, each encoded by a separate gene. These LPL receptor genes are also sometimes referred to as "Edg".

<span class="mw-page-title-main">Autotaxin</span>

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2, is an enzyme that in humans is encoded by the ENPP2 gene.

Lysophosphatidic acid receptor 1 also known as LPA₁ is a protein that in humans is encoded by the LPAR1 gene. LPA₁ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

Sphingosine-1-phosphate receptor 3 also known as S1PR3 is a human gene which encodes a G protein-coupled receptor which binds the lipid signaling molecule sphingosine 1-phosphate (S1P). Hence this receptor is also known as S1P₃.

Lysophosphatidic acid receptor 4 also known as LPA₄ is a protein that in humans is encoded by the LPAR4 gene. LPA₄ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

Lysophosphatidic acid receptor 2 also known as LPA₂ is a protein that in humans is encoded by the LPAR2 gene. LPA₂ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

Lysophosphatidic acid receptor 6, also known as LPA₆, P2RY5 and GPR87, is a protein that in humans is encoded by the LPAR6 gene. LPA₆ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

Lysophosphatidic acid receptor 5 also known as LPA₅ is a protein that in humans is encoded by the LPAR5 gene. LPA₅ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

Lysophosphatidic acid receptor 3 also known as LPA₃ is a protein that in humans is encoded by the LPAR3 gene. LPA₃ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).

Lipid phosphate phosphohydrolase 1 also known as phosphatidic acid phosphatase 2a is an enzyme that in humans is encoded by the PPAP2A gene.

Lipid phosphate phosphohydrolase 3 (LPP3), also known as phospholipid phosphatase 3 (PLPP3) and phosphatidic acid phosphatase type 2B, is an enzyme that in humans is encoded by the PPAP2B gene on chromosome 1. It is ubiquitously expressed in many tissues and cell types. LPP3 is a cell-surface glycoprotein that hydrolyzes extracellular lysophosphatidic acid (LPA) and short-chain phosphatidic acid. Its function allows it to regulate vascular and embryonic development by inhibiting LPA signaling, which is associated with a wide range of human diseases, including cardiovascular disease and cancer, as well as developmental defects. The PPAP2B gene also contains one of 27 loci associated with increased risk of coronary artery disease.

The human gene AGK encodes the enzyme mitochondrial acylglycerol kinase.

Neutral cholesterol ester hydrolase 1 (NCEH) also known as arylacetamide deacetylase-like 1 (AADACL1) or KIAA1363 is an enzyme that in humans is encoded by the NCEH1 gene.

Gintonin is a glycolipoprotein fraction isolated from ginseng. The non-saponin ingredient was designated as gintonin, where gin was derived from ginseng, ton from the tonic effects of ginseng, and in from protein. The main component of gintonin is a complex of lysophosphatidic acids (LPA) and ginseng proteins such as ginseng major latex-like protein151 (GLP151) and ginseng ribonuclease-like storage protein.

<span class="mw-page-title-main">Diglyceride</span> Type of fat derived from glycerol and two fatty acids

A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as surfactants and are commonly used as emulsifiers in processed foods. DAG-enriched oil has been investigated extensively as a fat substitute due to its ability to suppress the accumulation of body fat; with total annual sales of approximately USD 200 million in Japan since its introduction in the late 1990s till 2009.

Lysophosphatidic acid phosphatase type 6 is an acid phosphatase enzyme that is encoded in humans by the ACP6 gene.

The lysophosphatidic acid receptors (LPARs) are a group of G protein-coupled receptors for lysophosphatidic acid (LPA) that include:

References

↑ van Corven, Emile J.; Groenink, Alida; Jalink, Kees; Eichholtz, Thomas; Moolenaar, Wouter H. (1989-10-06). "Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins". Cell. 59 (1): 45–54. doi:10.1016/0092-8674(89)90868-4. PMID 2551506. S2CID 25154850.
↑ Tsukahara, Tamotsu; Tsukahara, Ryoko; Haniu, Hisao; Matsuda, Yoshikazu; Murakami-Murofushi, Kimiko (2015-09-05). "Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma". Molecular and Cellular Endocrinology. 412: 320–329. doi:10.1016/j.mce.2015.05.021. hdl: 10069/35888 . ISSN 0303-7207. PMID 26007326. S2CID 10454566.
↑ Moolenaar, Wouter H. (1995-06-02). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger ∗". Journal of Biological Chemistry. 270 (22): 12949–12952. doi: 10.1074/jbc.270.22.12949 . ISSN 0021-9258. PMID 7768880.
↑ Tigyi, Gabor; Parrill, Abby L. (2003-11-01). "Molecular mechanisms of lysophosphatidic acid action". Progress in Lipid Research. 42 (6): 498–526. doi:10.1016/S0163-7827(03)00035-3. ISSN 0163-7827. PMID 14559069.
↑ Benesch, MG; Ko, YM; McMullen, TP; Brindley, DN (2014). "Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions". FEBS Letters. 588 (16): 2712–27. doi: 10.1016/j.febslet.2014.02.009 . PMID 24560789. S2CID 35544825.