Using rates of amino acid flux to determine wholebody protein turnover

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As noted earlier in this section, investigators are faced with several choices regarding measurements of amino acid flux and protein turnover. One of the more widely applied methods for quantifying amino acid and protein turnover centres on the use of a primed-infusion of [1-13C]leucine (Figure 10.2). The flux of an amino acid (e.g. leucine) is described using the equation:

where Q is the rate of amino acid turnover in plasma (or the flux), S is the rate of incorporation of the amino acid into protein, C is the rate of amino acid oxidation (or catabolism), B is the rate of amino acid release from protein breakdown and I is the rate of exogenous intake of an amino acid (typically from the diet). In cases where subjects are studied in postabsorptive state, I = 0 and Q = B. Q and C are experimentally determined from the dilution of the infused tracer (e.g. [1-13C]leucine) and the rate of production of expired 13CO2 respectively; S is then calculated by solving the equation, i.e. S = Q - C.

The approach outlined above provides a measure of amino acid flux and whole-body protein turnover. In their seminal study, Matthews et al. (1980) thoroughly discuss the determination of these parameters during the infusion of [1-13C]leucine; their report also considers the extent to which analytical error(s) could impact the data. Although subsequent studies suggested that a multicompartmental model yields a more accurate determination

Figure 10.2 'Black Box' Model of Protein and Amino Acid Metabolism Studies often consider a two-pool model of protein and amino acid dynamics. Assuming a constant mass of free amino acids, different tracer methods (e.g. [1-13C]leucine or [15N]glycine) can be used to quantify the various flux rates in fasted or fed subjects.

Figure 10.2 'Black Box' Model of Protein and Amino Acid Metabolism Studies often consider a two-pool model of protein and amino acid dynamics. Assuming a constant mass of free amino acids, different tracer methods (e.g. [1-13C]leucine or [15N]glycine) can be used to quantify the various flux rates in fasted or fed subjects.

of leucine kinetics (Cobelli et al. 1991), investigators typically rely on simpler 'primary' (Matthews et al. 1980) or 'reciprocal' (Horber et al. 1989; Matthews et al. 1982) models. It is important to note that determination of 13CO2 production is complicated by the fact that 13CO2 molecules will exchange with unlabeled CO2 and be deposited in the body; Matthews and others have addressed this matter (Downey et al. 1986; Toth et al. 2001).

Numerous tracer studies of leucine flux and whole-body protein turnover have been performed in diabetic subjects. The data suggest a tendency for increased protein breakdown in poorly controlled type 1 diabetics, and that intensive insulin therapy normalises leucine flux in most cases (Luzi et al. 1990; Lariviere et al. 1992). It appears that insulin action on whole-body protein turnover plays a greater role in modulating splanchnic vs leg muscle protein turnover in vivo (Nair et al. 1995). In contrast to studies done in type 1 diabetics, there appears to be some discrepancy regarding leucine flux and protein turnover in those with type 2 diabetes and related conditions. For example, studies performed in subjects with type 2 diabetes report no alterations in leucine flux during basal or insulin-stimulated conditions in patients with impaired regulation of glucose metabolism (Luzi et al. 1993). However, studies done in the offspring of patients with type 2 diabetes found evidence of impaired insulin-mediated suppression of leucine appearance, comparable to that observed for the defect in insulin-stimulated glucose metabolism (Lattuada et al. 2004). Investigators have also demonstrated impaired insulin-mediated activation of whole-body protein synthesis in obese insulin-resistant women (Chevalier et al. 2005). Clearly, the discrepancies between the data reported in various states of insulin resistance may reflect different patient populations and/or variable degrees of disease.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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