Lysophosphatidic acid

Lysophosphatidic acid

Lysophosphatidic acid
Names
IUPAC name
(2-hydroxy-3-phosphonooxypropyl) (Z)-octadec-9-enoate
Other names
LPA
Identifiers
 Y
Jmol-3D images Image
MeSH
PubChem
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).
 Y  (: Y/N?)

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

Contents

  • Function 1
  • Clinical significance 2
  • GTPase activation 3
  • Metabolism 4
  • See also 5
  • References 6
  • Further reading 7

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.

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.

Production of LPA by Autotaxin

See also

References

  1. ^ Reginald Garrett; Charles M. Grisham (28 December 2008). Biochemistry. Cengage Learning. pp. 235–.  

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.  
  • Moolenaar, Wouter H. (1995). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger". The Journal of Biological Chemistry 270 (22): 12949–52.  
  • Mills, Gordon B.; Moolenaar, Wouter H. (2003). "The emerging role of lysophosphatidic acid in cancer". Nature Reviews Cancer 3 (8): 582–91.  
  • 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.  
  • 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.