Protein degradation during fasting

Saundersoa C.L. Leslie, S. (1988). Muscle growth and protein degradation during early development in chicks of fast and slow growing strains. Comp. Biochem. Physiol, 89A, 333-7. 

D. Skeletal muscle in its resting state can satisfy most of its energy needs by oxidation of fatty acids taken up from blood, and during the early stages of fasting, protein degradation in the muscle is increased. 

Up to one-third of muscle protein may be degraded to component amino acids for use as fuel during fasting. 

Skeletal muscle is specialized to perform intermittent mechanical work. As described previously, the energy sources that provide ATP for muscle contraction depend on the degree of muscular activity and the physical status of the individual. During fasting and prolonged starvation, some skeletal muscle protein is degraded to provide amino acids (e.g., alanine) to the liver for gluconeogenesis. 

During fasting or infective stress, protein degradation in skeletal muscle is activated to increase the supply of amino acids in the blood for glu-coneogenesis, or for the synthesis of antibodies and other component of the immune response. Under these conditions, synthesis of ubiquitin, a protein that targets proteins for degradation in proteosomes, is increased by the steroid hormone cortisol. 

The brain is glucose dependent, but, like many cells in the body, can use BCAA for energy. The BCAA also provide a source of nitrogen for neurotransmitter synthesis during fasting. Other amino acids released from skeletal muscle protein degradation also serve as precursors of neurotransmitters. 

In these hypercatabolic states, skeletal muscle protein synthesis decreases, and protein degradation increases. Oxidation of BCAA is increased and glutamine production enhanced. Amino acid uptake is diminished. Cortisol is the major hormonal mediator of these responses, although certain cytokines may also have direct effects on skeletal muscle metabohsm. As occurs during fasting and metabolic acidosis, increased levels of cortisol stimulate ubiquitin-mediated proteolysis, induce the synthesis of glutamine synthetase, and enhance release of amino acids and glutamine from the muscle cells. 

The presence of proteases is a threat for protein stability. A simple strategy for protection against proteolytic degradation is based on the fast handling of the sample and use of low temperatures. One additional precaution is the addition of protease inhibitors, especially during disruption and extraction steps. In some cases, there is a need for a combination of inhibitors. Sometimes, pH adjustment is effective in inactivating proteases without affecting the stability of the protein product. 

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