L-amino acid sensing by CaSR and Physiological Impact on Mice.
(2014) KBK820 20142Pure and Applied Biochemistry
- Abstract
- After localizing of the extracellular calcium sensing receptor (CaSR) throughout the gastrointestinal tract, free aromatic L-amino acids have been found to act as positive allosteric modulators suggesting the CaSR is a potential mediator in protein digestion. The binding site for L-amino acids in the CaSR is located in the venus flytrap domain (VFD). Point mutations on residue Thr-145 and Ser-170 in the venus flytrap domain (VFD), holding binding site(s) for L-amino acids, together, stereo selectively impairs and disables L-amino acid sensing while leaving Ca2+-sensing intact. In this study, we investigated if knock-in mice (KI) with double mutation T145A/S170T in the CaSR leads to increased food intake and weight gain due to probable... (More)
- After localizing of the extracellular calcium sensing receptor (CaSR) throughout the gastrointestinal tract, free aromatic L-amino acids have been found to act as positive allosteric modulators suggesting the CaSR is a potential mediator in protein digestion. The binding site for L-amino acids in the CaSR is located in the venus flytrap domain (VFD). Point mutations on residue Thr-145 and Ser-170 in the venus flytrap domain (VFD), holding binding site(s) for L-amino acids, together, stereo selectively impairs and disables L-amino acid sensing while leaving Ca2+-sensing intact. In this study, we investigated if knock-in mice (KI) with double mutation T145A/S170T in the CaSR leads to increased food intake and weight gain due to probable decreased secretions of anorectic hormones and hence decreased sensation of fullness. Comparison with wild-type (WT) mice showed KI-mice weighed significantly more after nine weeks of age (p < 0.001) and consumed more feed when given a diet with casein-based protein content (p < 0.01). The present data suggest that the CaSR may serve as a potential regulator and mediator in dietary protein and food intake regulation, making it a potential therapeutic target in treating obesity. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/4732901
- author
- Larsson, Anna LU
- supervisor
- organization
- course
- KBK820 20142
- year
- 2014
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Calcium Sensing Receptor, L-Amino Acids, Protein-Leverage Hypothesis
- language
- English
- id
- 4732901
- date added to LUP
- 2014-12-19 12:39:38
- date last changed
- 2015-01-22 18:03:59
@misc{4732901, abstract = {{After localizing of the extracellular calcium sensing receptor (CaSR) throughout the gastrointestinal tract, free aromatic L-amino acids have been found to act as positive allosteric modulators suggesting the CaSR is a potential mediator in protein digestion. The binding site for L-amino acids in the CaSR is located in the venus flytrap domain (VFD). Point mutations on residue Thr-145 and Ser-170 in the venus flytrap domain (VFD), holding binding site(s) for L-amino acids, together, stereo selectively impairs and disables L-amino acid sensing while leaving Ca2+-sensing intact. In this study, we investigated if knock-in mice (KI) with double mutation T145A/S170T in the CaSR leads to increased food intake and weight gain due to probable decreased secretions of anorectic hormones and hence decreased sensation of fullness. Comparison with wild-type (WT) mice showed KI-mice weighed significantly more after nine weeks of age (p < 0.001) and consumed more feed when given a diet with casein-based protein content (p < 0.01). The present data suggest that the CaSR may serve as a potential regulator and mediator in dietary protein and food intake regulation, making it a potential therapeutic target in treating obesity.}}, author = {{Larsson, Anna}}, language = {{eng}}, note = {{Student Paper}}, title = {{L-amino acid sensing by CaSR and Physiological Impact on Mice.}}, year = {{2014}}, }