Whole-Body Protein Turnover and Energy Metabolism in Man

Abstract

This thesis consists of 2 major parts - Part A on whole-body protein turnover in humans, and Part B on energy metabolism. The method primarily used for measurement of whole-body protein turnover in this thesis has been with the constant infusion of (1-14C) leucine, and this method is tested, analysed, and developed for extended 24 - 40 hour continuous protein turnover measurements. Using this method, it was found that protein intake has a dramatic and controlling influence on protein synthesis. This is initially established in Section 3. In Section 4, it is shown that protein synthesis, breakdown, and oxidation are acutely responsive to protein intake, with large diurnal fluctuations resulting from feeding/fasting patterns. Protein turnover is compared in obese and lean humans, amino acid pool changes and the question of circadian rhythms examined. Section 5 compares results from the (1-14C) leucine method with those of (15N)glycine, and long term changes in protein turnover are monitored. Section 6 shows how remarkable adaptive changes occur in protein synthesis and breakdown, resulting from a prolonged absence of protein intake. Thus the relationship between whole-body protein turnover and protein intake is examined and established. In Part B, techniques developed for the (1-14C) leucine method are exploited to measure by indirect calorimetry acute changes in the net synthesis and utilisation of glucose and fat. It is suggested that traditional methodology and restrictive current concepts concerning the use of indirect calorimetry have limited its development. Formulae are derived, which allow calculation of net fuel transfers under most conditions, and these formulae and (1-14C) leucine techniques are combined to measure the body's response to different levels of carbohydrate intake, in both obese and non-obese humans.