Lysophosphatidic acid

Lysophosphatidic acid
Names
	IUPAC name (2-hydroxy-3-phosphonooxypropyl) (Z)-octadec-9-enoate
	Other names LPA
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).

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

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.^[2]

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.

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.
^ 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.

Kremer, Andreas E.; Martens, Job J.W.W.; Kulik, Wim; Ruëff, Franziska; Kuiper, Edith M.M.; Van Buuren, Henk R.; Van Erpecum, Karel J.; Kondrackiene, Jurate; et al. (2010). "Lysophosphatidic Acid is a Potential Mediator of Cholestatic Pruritus". Gastroenterology. 139 (3): 1008–18, 1018.e1. doi:10.1053/j.gastro.2010.05.009. PMID 20546739.
Moolenaar, Wouter H. (1995). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger". The Journal of Biological Chemistry. 270 (22): 12949–52. doi:10.1074/jbc.270.22.12949. PMID 7768880.
Mills, Gordon B.; Moolenaar, Wouter H. (2003). "The emerging role of lysophosphatidic acid in cancer". Nature Reviews Cancer. 3 (8): 582–91. doi:10.1038/nrc1143. PMID 12894246. S2CID 29079135.
Panupinthu, N; Lee, H Y; Mills, G B (2010). "Lysophosphatidic acid production and action: Critical new players in breast cancer initiation and progression". British Journal of Cancer. 102 (6): 941–6. doi:10.1038/sj.bjc.6605588. PMC 2844037. PMID 20234370.
Park, S Y; Jeong, K J; Panupinthu, N; Yu, S; Lee, J; Han, J W; Kim, J M; Lee, J-S; et al. (2010). "Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression". Oncogene. 30 (11): 1351–9. doi:10.1038/onc.2010.517. PMID 21102517.

[1] 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.

[2] 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.

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