Muscle protein degradation

Mechanism of Action. P-Agonists stimulate skeletal muscle growth by accelerating rates of fiber hypertrophy and protein synthesis, but generally do not alter muscle DNA content in parallel with the increases in protein accretion (133—135). This is in contrast to the effects of anaboHc steroids and ST on skeletal muscle growth. Both of the latter stimulate fiber hypertrophy and muscle protein synthesis, but also increase muscle DNA content coincident with increased protein accretion. Whether the P-agonists decrease muscle protein degradation is equivocal. 

Initially the level of insulin decreases, favouring increased rates of lipolysis, fatty acid oxidation, muscle protein degradation, glycogenolysis and gluconeogenesis. It soon increases, however, as a result of insulin resistance, when the stimulation of the above processes will depend on the cytokine levels. For details of endocrine hormone effects, see Chapter 12. For details of cytokines see Chapter 17. 

Tisdale, M. J. (1996). Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachesia. WuJrftibn 12, S31-S33-... 

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. 

Paul, H.S., and S.A. Adibi. 1980. Leucine oxidation and protein turnover in clofibrate-induced muscle protein degradation in rats. 65 1285-93. 

Brault JJ, Jespersen JG, Goldberg AL. (2010) Peroxisome proliferator-activated receptor gamma coactivator lalpha or Ibeta overexpression inhibits muscle protein degradation, induction of ubiquitin Ugases, and disuse atrophy. J Biol Chem 285, 19460-19471. 

In conclusion, this study shows that the expression of atrogin-l/MAFbx and C2 subunit mRNA in skeletal muscle of broilers was lower than in layers, suggesting lower muscle protein degradation in broiler than in layer chicken, responsible for the increased muscle mass. These results indicate that... 

Mammals, fungi, and higher plants produce a family of proteolytic enzymes known as aspartic proteases. These enzymes are active at acidic (or sometimes neutral) pH, and each possesses two aspartic acid residues at the active site. Aspartic proteases carry out a variety of functions (Table 16.3), including digestion pepsin and ehymosin), lysosomal protein degradation eathepsin D and E), and regulation of blood pressure renin is an aspartic protease involved in the production of an otensin, a hormone that stimulates smooth muscle contraction and reduces excretion of salts and fluid). The aspartic proteases display a variety of substrate specificities, but normally they are most active in the cleavage of peptide bonds between two hydrophobic amino acid residues. The preferred substrates of pepsin, for example, contain aromatic residues on both sides of the peptide bond to be cleaved. 

The alanine cycle accomplishes the same thing as the Cori cycle, except with an add-on feature (Fig. 17-11). Under conditions under which muscle is degrading protein (fasting, starvation, exhaustion), muscle must get rid of excess carbon waste (lactate and pyruvate) but also nitrogen waste from the metabolism of amino acids. Muscle (and other tissues) removes amino groups from amino acids by transamination with a 2-keto acid such as pyruvate (oxaloacetate is the other common 2-keto acid). 

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

The situation is, however, different in starvation. In this condition, it is the degradation of muscle protein that provides the amino acids for gluconeo-genesis, so that all the oxo-acids generated (except those for lysine and lencine) are nsed to synthesise the glucose required for oxidation by the brain. Hence, a process other than amino acid oxidation mnst generate the ATP required by gluconeogenesis. This process is fatty acid oxidation. 

Figure 8.13 The central role of transdeamination in metabolism of amino adds and further metabolism of the oxoacids in the liver. The box contains the reactions for conversion of the amino acids to their respective oxoacids. Processes are as follows (1) digestion of protein in the intestine and absorption of resultant amino acids, (2) degradation of endogenous protein to amino acids (primarily but not exclusively muscle protein), (3) protein synthesis, (4) conversion of amino acid to other nitrogen-containing compounds (see Table 8.4), (5) oxidation to CO2, (6) conversion to glucose via gluconeogenesis, (7) conversion to fat.

The amino acid precursors for gluconeogenesis are provided from the degradation of muscle protein. 

Figure 16.11 Pattern of fuel utilisation during prolonged starvation. The major metabolic change during this period is that the rates of ketone body formation and their utilisation by the brain increases, indicated by the increased thickness of lines and arrows. Since less glucose is required by the brain, gluconeogenesis from amino acids is reduced so that protein degradation in muscle is decreased. Note thin line compared to that in Figure 16.9.

In normal young children, the contribution of amino acid oxidation to energy requirement in starvation is about 1%, similar to that in the obese. In malnourished children, who have a protein-energy deficiency, it is even lower (4%). This suggests that a mechanism exists to protect muscle protein from degradation in children. Such a mechanism may involve a faster and greater increase in ketone body formation in children compared with adults (Chapter 7). 

The amino acids that are made available as a result of protein degradation in starvation are nsed as precursors of glucose, which is required for the brain. The decline in starvation-induced protein degradation is a result of the decreased requirement for glucose by the brain due to the increase in utilisation of ketone bodies. The qnestion arises, therefore, as to the mechanism by which the protein breakdown in muscle is reduced. Two answers, which are interdependent, have been put forward (i) decreased metabolic activity in tissues, and (ii) a decrease in the plasma level of thyroxine and hence triiodothyronine. 

Figure 17.20 Cytokines produced by activated Th cells and some of their effects. The cytokines produced have several functions activation of B-cells, macrophages and cytotoxic T-cells. The cytokines, along with endocrine hormones, stimulate responses in the whole body (e.g. lipolysis in adipose tissue, protein degradation in muscle, acute phase protein production in liver. Chapter 18).

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