Leucine metabolism in stable cirrhosis

This review is concerned with rates of N flux in the living animal rather than with mechanisms of protein synthesis and breakdown at the cellular level. Methods of measuring protein turnover in the whole body are discussed, with special emphasis on studies in man, and results obtained by different methods have been compared. Aspects of whole body protein turnover which are of physiological interest include its relation to body size, growth and development, energy metabolism and food intake. There are substantial increases in protein turnover in injury, and changes that occur in exercise are beginning to be explored. From the physiological point of view these results point the need for future research along two main lines. The first is that of regulation: a wide variety of hormones stimulate or repress protein synthesis and breakdown, with varying actions in different tissues. These effects, however, do not in themselves explain the mechanism by which a balance between synthesis and breakdown is maintained. Secondly, the fact that all cellular proteins are in a dynamic state poses questions about the relation between structure and function in tissues such as muscle and brain, which physiologists have hardly begun to tackle.

The keto analog of leucine, alpha-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore. KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg-1d-1) to deficient (0.0 g kg-1d-1) for 5-7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-13C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-13C]leucine infusions, the ratio of [1-13C]KIC to [1-13C]leucine enrichment ratio remained relatively constant (77 +/- 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine 13C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.