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Undergraduate Research Project Management System

The Role of Leucine and BCAAs in Regulating Protein Synthesis

Status Current
Seeking Researchers No
Start Date 09/01/2008
End Date 06/30/2009
Funding Source Alaska Heart Institute Fellowships
Funding Amount
Community Partner
Related Course
Last Updated 07/05/2008 01:25AM
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Faculty
  Tim Hinterberger

Student Researchers
  Alex Bonnecaze

Abstract

Leucine, isoleucine, and valine make up a distinct class of amino acids known as branched chain amino acids (BCAAs). BCAAs, especially leucine, have been shown to increase protein synthesis in skeletal muscle cells by activating the mammalian target of rapamycin (mTOR), a protein kinase. Leucine has also been show to directly increase the concentration of key initiation factors for protein synthesis, such as eIF4G. In addition to stimulating protein synthesis in muscle cells, leucine also slows protein degradation by binding to ubiquitin (Ub) proteasomes and preventing proteolysis. While leucine appears to be the main BCAA involved in increasing skeletal muscle protein synthesis, studies have determined that the addition of leucine without the other two BCAAs has a potential negative impact. The cellular presence of any of the three BCAAs activates branched chain ketoacid dehydrogenase (BCKD), an enzyme breaks down all three of the BCAAs. Due to the activity of BCKD it is generally believed that leucine should be administered in a proper ratio with the other BCAAs to avoid an imbalance. Muscle cells in a starved or exhausted state respond the most to the addition of BCAAs. While much has been learned about BCAAs' impact on skeletal muscle cells, many questions remain unanswered. Using C2C12 and L6 cells, two cultured cell lines that are widely studied models of normal skeletal muscle, we will determine what ratio of leucine to other BCAAs best stimulates protein synthesis. C2C12 and L6 myotubes will be tested in multiple trials involving the addition of BCAAs in different concentration ratios. Whether or not insulin synergistically works with BCAAs to increase protein synthesis will also be tested. We will also determine if leucine has any effect on the level of the myogenic factor MRF4 protein, because increased MRF4 has previously been found to be associated with muscle growth. If MRF4 protein is increased, the possibility that these treatments increase levels of MRF4 gene transcripts will be examined.

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