Biochemical approaches for nutritional support of skeletal muscle protein metabolism during sepsis

Abstract

Sepsis initiates a unique series of modifications in the homeostasis of N metabolism and profoundly alters the integration of inter-organ cooperatively in the overall N and energy economy of the host. The net effect of these alterations is an overall N catabolic state, which seriously compromises recovery and is semi-refractory to treatment with current therapies. These alterations lead to a functional redistribution of N (amino acids and proteins) and substrate metabolism among injured tissues and major body organs. The redistribution of amino acids and proteins results in a quantitative reordering of the usual pathways of C and N flow within and among regions of the body with a resultant depletion of the required substrates and cofactors in important organs. The metabolic response to sepsis is a highly integrated, complex series of reactions. To understand the regulation of the response to sepsis, a comprehensive, integrated analysis of the fundamental physiological relationships of key metabolic pathways and mechanisms in sepsis is essential. The catabolism of skeletal muscles, which is manifested by an increase in protein degradation and a decrease in synthesis, persists despite state-of-the-art nutritional care. Much effort has focused on the modulation of the overall amount of nutrients given to septic patients in a hope to improve efficiencies in utilisation and N economies, rather than the support of specific end-organ targets. The present review examines current understanding of the processes affected by sepsis and testable means to circumvent the sepsis-induced defects in protein synthesis in skeletal muscle through increasing provision of amino acids (leucine, glutamine, or arginine) that in turn act as nutrient signals to regulate a number of cellular processes.