1 2 3 4 5 6 Alterations in Glutamine Metabolism and Its Conversion to Citrulline in Sepsis

32 33 In enterocytes, glutamine serves as the major source of energy; another metabolic fate of glutamine is 34 conversion to citrulline. Because sepsis can affect gut function and integrity, alterations in glutamine 35 metabolism may exist and lead to decreased citrulline production. This study aimed to investigate how 36 sepsis affects glutamine metabolism, including its conversion to citrulline, by measuring glutamine and 37 citrulline flux, fractional splanchnic extraction of glutamine and leucine, and the contribution of 38 glutamine nitrogen to citrulline in septic patients and healthy controls. Eight patients with severe sepsis 39 and 10 healthy controls were given primed, constant intravenous infusion of H2-citrulline and sequential 40 administration of intravenous and enteral α-N-glutamine and C-leucine in the postabsorptive state. 41 The results showed that compared with healthy controls, septic patients had a significantly lower whole42 body citrulline flux and plasma concentration, higher endogenous leucine flux, and higher glutamine 43 clearance. Fractional splanchnic extraction of leucine was higher in septic patients compared with 44 controls, but fractional extraction of glutamine was not different. The majority of the N label 45 transferred from glutamine to citrulline was found at the alpha position. These results demonstrate that 46 lower glutamine plasma concentrations in sepsis were a result of increased glutamine clearance. Despite 47 adequate splanchnic uptake of glutamine, there is decreased production of citrulline, suggesting a defect 48 in the metabolic conversion of glutamine to citrulline, decreased uptake of glutamine by the enterocyte 49 but increased uptake by the liver, and/or shunting of glutamine to other metabolic pathways. 50 51