ABSENCE OF GLUTAMINE ISOTOPIC STEADY-STATE - IMPLICATIONS FOR THE ASSESSMENT OF WHOLE-BODY GLUTAMINE PRODUCTION-RATE

1. During infusion of [5-N-15]glutamine in patients with gastrointesti nal cancer we unexpectedly observed a gradual decrease in time of the appearance rate (R-a) of glutamine in plasma. Here we investigate whet her the failure to achieve a plateau isotopic enrichment in plasma is, among other factors, due to incomplete equilibration of the glutamine tracer with the large intramuscular free glutamine pool. 2. Plasma an d intramuscular glutamine en rich ment were measured during 6-11 h inf usions of L-[5-N-15]glutamine and L-[1-C-13]glutamine in post-absorpti ve patients admitted to hospital for elective abdominal surgery. L-[1- C-13]Leucine and L-[ring-H-2(5)]phenylalanine were infused to measure the proportion of glutamine appearing in plasma directly due to its re lease from protein. 3. The glutamine tracer entered muscle, but the ri se in intramuscular glutamine enrichment was small, presumably as a re sult of the enormous size of the intramuscular glutamine pool and the limited speed of entry of glutamine into muscle. In each patient the i ntramuscular glutamine enrichment was lower than that in plasma (P< 0. 001), and both increased with tracer infusion time (P < 0.001), indica ting incomplete equilibration of the glutamine tracer. 4. A comparison of the results obtained by the two glutamine tracers indicated that r ecycling of the nitrogen label contributed to about 15% of the decreas e in R-a. 5. There was a gradual reduction in the glutamine release fr om proteolysis, which contributed to 16-21 % of the decline in R-a. 6. We conclude that slow equilibration of the glutamine tracer with the large muscle glutamine pool significantly contributes to the absence o f isotopic steady state. Consequently, the appearance rate of glutamin e in plasma measured during short tracer infusion periods (hours) cons iderably overestimates the whole-body glutamine flux.