Mechanisms of altered protein turnover in chronic diseases: a review of human kinetic studies

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Abstract
Changes in hormone secretion, tissue perfusion, oxygen availability, energy-protein intake, free amino acid pattern, hydration state, acid-base balance as well as activation of the systemic inflammatory response may affect protein synthesis and degradation. The overall purpose of this review is to describe how these factors may interact to change protein turnover in the different directions seen in kinetic studies in humans. Evidence indicates that, in vivo, changes of protein synthesis and degradation are strictly related. When protein synthesis is primarily suppressed, protein degradation is found to be unchanged or even slightly decreased. When protein degradation is primarily accelerated, the rate of synthesis is unchanged or even increased. Chronic disease states can, therefore, be characterized either by decreased or accelerated protein turnover. Apparent discrepancies among various studies in chronic uraemia, liver cirrhosis, chronic obstructive pulmonary disease and cancer may stem from the fact that the pathogenesis of protein metabolism abnormalities is multifactorial. When the effects of inflammatory mediators and stress hormones start overwhelming factors that tend to decrease protein synthesis and turnover (decreased protein-energy intake, physical activity, tissue oxygen delivery, leucine levels, etc.), the rate of protein degradation and turnover may increase. Low-protein turnover conditions are usually associated with the adequate sparing of body proteins, whereas in high-protein turnover conditions protein loss may proceed at a faster rate. Nonetheless, impaired recovery from acute complications and the reduced renewal of damaged and toxic proteins are potential undesired consequences of low-protein turnover.