The acute changes in intracellular amino acid production during sepsis do not relate to plasma concentrations

It remains unclear how amino acid metabolism is altered during the early phase of sepsis. We therefore investigated the acute changes in amino acid metabolism during sepsis in a pig model. We studied 51 pigs using a pulse stable isotope tracer method to measure kinetic changes in almost all amino acids before and 6.5 h after sepsis induction by continuous infusion of Pseudomonas aeruginosa. Statistics were done by Generalized Linear Mixed Model. Sepsis induced only small (<10 %) changes in plasma concentration of amino acids, while amino acid clearance was substantially increased for amino acids like taurine (+33 %), histidine (+42 %), glycine (+35 %), glutamine (+27 %), arginine (+13 %) and citrulline (+20 %), while reduced for tyrosine (-11 %), threonine (-11 %), lysine (-14 %). Compartmental analysis revealed that changes in extra- and intracellular amino acid pools and fluxes were much larger than the changes in plasma concentrations. Intracellular pool sizes were substantially lower for glutamate (-47 %), lysine (-46 %), phenylalanine (-39 %), threonine (-33 %), and tyrosine (-28 %) and higher for taurine (+21 %), hydroxyproline (+31 %) and glutamine (+35 %). Notably, intracellular productions of essential amino acids like lysine (-49 %), phenylalanine (-25 %), threonine (-26 %), tryptophan (-22 %), and tyrosine (-22 %) were significantly reduced during sepsis, while those of taurine (+24 %) and glutamine (+34 %) were increased, suggesting attenuated protein breakdown in the early phase of sepsis. Plasma cytokine levels, including IL1-beta (+50 %), IL1-ra (+120 %), IL6 (+26 %), and TNF-alpha (+9 %), were also statistically significantly elevated. Large changes in intracellular amino acid metabolism occur relatively quickly during the development of sepsis, while changes in plasma concentration are small. Therefore, compartmental analysis of amino acid metabolism shows that changes in the extra- and intracellular pools and fluxes into these pools seems to precede the changes in plasma concentrations, indicating that amino acid metabolism is affected much more and sooner than could be concluded from measuring plasma concentrations only.