Sandbox Reserved 1175

This Sandbox is Reserved from Jan 11 through August 12, 2016 for use in the course CH462 Central Metabolism taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1160 through Sandbox Reserved 1184.

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Lysophosphatodic Acid

Figure 1: Chemical Structure of LPA

Function

LPA, a signaling phospholipid, can attach to three specific G-protein-coupled receptors. LPA can activate multiple pathways in particular, Ras and Pho which belong to the family of GTPases. Another use of LPA is it can help in stimulation of cell migration .

Helices

Structure

spinqualitylabelsall models LPA Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Comparison of S1P and LPA Lysophosphatidic Acid Receptors (LPA) are part of a larger family known as lysophospholipid receptor family (EDG family). Within this family there is a structure called S1P1. Since only the structures for LPA1 and S1P1 are known in the EDG family, comparisons are made between the two structures . There is a difference in binding paths between these two receptors. The binding path in the LPA1 is located in the extracellular milieu. While in the S1P1 the ligands are able to have access to the membrane so that the binding can occur. Figure 2: Comparison of the binding pockets of LPA1 and S1P1 receptors There is a difference in the shape of the electron density from the binding pocket. In S1P1 the binding pocket has more of an oval shape. For the LPA1 receptor the binding pocket has a spherical shape. Since the binding pocket is more spherical it gives LPA1 the ability to be able to recognize a larger group of chemical species. In particular the ability to bind with acyl chains of varying lengths . Clinical Testing LPA is still in the clinical stage of testing. So far the LPA receptors have had physiological effects on every organism that it has been tested with. There have been studies done looking at what happens with infertility, fibrosis, pain, and cancer when they come into contact with LPA receptors ,ref name= "Chrencik"/>. LPA receptors are commonly found in serum and saliva. . Pain LPA, a signaling phospholipid, that attaches to three specific G-protein-coupled receptors. After an injury occurs LPA is released in the body. It then will activate G-protein-coupled receptors. Within the nervous system, LPA plays a role in the nociceptive process (nociceptive pain is a sharp pain that can come from a mild burn or twisted ankle). The LPA signaling will activate GTPase RhoA. Once activated Rho translocates to the plasma membrane. Rho will activate Rho kinase (ROCK). Mice with the deletation of LPA1 receptors were studied to see the role that LPA signaling played in pain. In a study done with mice, those without the LPA1 receptor had lower levels of pain.. Another use of LPA is it can help in stimulation of cell migration . It was seen that with targeted deletion of LPA receptors the mice would be cured from fibrosis. Mice who had fibrosis were given LPA1 regulated LPA-induced fibroblast. Over time the mice who had fibrosis began to have their lungs repaired. The amount of fluid in their lungs decreased.