Immunonutrition: role of sulfur amino acids, related amino acids, and polyamines

Pro-inflammatory cytokines mediate widespread changes in protein metabolism. Amino acids released from peripheral tissues fulfill a number of functions. They act as substrate for acute phase protein and immunoglobulin synthesis and, together with polyamines, in the replication of immune cells. Demands for specific amino acids may outstrip the supply from endogenous sources. A number of strands of evidence suggest that sulphur amino acids, and amino acids that are metabolically related to them, may be required in increased amounts. Protein deficiency impairs the acute phase response. However, sulfur amino acid insufficiency compromises glutathione synthesis, to a greater extent than hepatic protein synthesis, in the presence and absence of an inflammatory stimulus. The resulting effect may be compromised antioxidant defences. Functioning of T cells is dependent on intracellular glutathione concentrations and may also be affected by sulphur amino acid insufficiency. It has been suggested that the increased N excretion, which occurs during the immune response, is a reflection of a relative imbalance in the profile of amino acids released from peripheral tissues and the requirements imposed by the synthesis of substances involved in the acute phase response. Phenylalanine, tyrosine, tryptophan serine, and cysteine are released in amounts closest to requirements. Polyamine synthesis may be important for the fidelity of the enhanced level DNA transcription and RNA translation that occurs in response to infection and during tissue repair, gut growth after surgery, and in gut barrier functions. Although synthesized de novo from ornithine, arginine and S-adenosyl methionine (SAM), substantial recycling is a key feature of polyamine metabolism. The recycling may be a reflection of the need to maintain adequate tissue SAM during periods of rapid cell growth. During an immune/inflammatory response the combination of enhanced utilization of cysteine for glutathione synthesis and cell replication may lead to depletion of cellular SAM. A relatively small addition of polyamines to the diet may improve gut-associated aspects of the hosts' antibacterial defenses.