From Wikipedia, the free encyclopedia
Chemical compound
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
ChEMBL
ChemSpider
ECHA InfoCard
100.040.631
EC Number
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
C21 H41 O7 P
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).
Chemical compound
A 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 lyso
phospholipase D called
autotaxin , which removes the
choline group from
lysophosphatidylcholine .
Lysophosphatidic acids are also intermediates in the synthesis of
phosphatidic acids .
See also
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 .
Further reading
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 .
Yakubu, M A; Liliom, K; Tigyi, G J; Leffler, C W (1997). "Role of lysophosphatidic acid in endothelin-1-and hematoma-induced alteration of cerebral microcirculation". 273 (2): R703–R709.
doi :
10.1152/ajpregu.1997.273.2.R703 .
Tigyi, G J; Hong, L; Yakubu, M; Parfenova, H; Shibata, M; Leffler, C W (1995). "Lysophosphatidic acid alters cerebrovascular reactivity in piglets". 268 (5): H2048–H2055.
doi :
10.1152/ajpheart.1995.268.5.H2048 .
Extracellular
Eicosanoids Lysophospholipids Steroids Others
Intracellular
Nuclear receptor
Second messenger
General:
Arachidonic acid
DAG (
PKC ,
TRPC )
IP3 (
IP3 R ,
RyR )
Phosphatidic acid
Phosphoinositides:
PIP2 (
IRKs )
PIP3 (
PKB/Akt ,
Btk ,
PDPK1 )
PtdIns(3,4)P2 (
PKB/Akt ,
PDPK1 ); Sphingolipids:
C1P
Ceramide (
CAPPs ,
KSR1 ,
PKCζ ,
CTSD )
Glucosylceramides
S1P
Sphingosine (
SDK1 ,
PKH ,
YPK )
Precursors