Lysophosphatidic acid
Names
Systematic IUPAC name
(2R)-2-hydroxy-3-{[(9Z)-octadec-9-enoyl]oxy}propyl dihydrogen phosphate
Other names
LPA
1-acyl-sn-glycerol 3-phosphate
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.040.631 Edit this at Wikidata
EC Number
  • 244-710-0
MeSH lysophosphatidic+acid
UNII
  • 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
  • CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(=O)(O)O)O
Properties
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).
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A lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.[1][2][3][4]

Function

See also: Lysophospholipid receptor

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 acids are also intermediates in the synthesis of phosphatidic acids.

Production of LPA by Autotaxin

See also

References

  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. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.

Further reading

Category