Investigating Amino Acid Activation of G Protein Couple Receptors Involved in Lipid Metabolism

Investigating Amino Acid Activation of G Protein Couple Receptors Involved in Lipid Metabolism
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Book Synopsis Investigating Amino Acid Activation of G Protein Couple Receptors Involved in Lipid Metabolism by : Madelaine D. Russell

Download or read book Investigating Amino Acid Activation of G Protein Couple Receptors Involved in Lipid Metabolism written by Madelaine D. Russell and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Energy homeostasis is a dynamic and complex process that maintains a balance between energy intake and expenditure. G protein coupled receptors (GPCRs), the largest family of transmembrane receptors, are critical for the cellular communication needed to coordinate processes involved in energy homeostasis (e.g. food intake). Indeed, metabolites are thought to act as sensors of energy stores by activating GPCRs in order to regulate energy homeostasis. Amino acids in particular have been shown to activate a growing number of GPCRs such as the calcium receptor (CaR), the orphan GPCRs GPR142 and GPR139, the purinergic receptor P2Y, and the hydroxycarboxylic acid receptor HCA3. This study aimed to further elucidate the role of monomeric amino acids as signaling molecules by employing a high throughput screen approach in which 19 monomeric amino acids were screened against 72 lipid metabolism GPCRs in a human cell line. Receptor activity was measured using the G-protein independent ?-arrestin recruitment PRESTO TANGO assay. It was found that a mixture of 19 essential and non-essential amino acids significantly activated 14 lipid metabolism GPCRs. Of these, MC4, DP2, GPBA, S1P1, and S1P4 were chosen for further investigation and were found to be significantly activated by 0.8 mM L-Phenylalanine. This finding suggests L-Phenylalanine may play a more prominent role as a signalling molecule at GPCRs regulating energy homeostasis than previously thought. This aids in elucidating the satiating mechanisms of high protein diets and has important implications for research into diseases such as obesity, type 2 diabetes, and the metabolic syndrome.


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Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get