L‐[2,3,3,4,5,5,5,6,6,6‐2H10]leucine improves accuracy of muscle protein synthesis determinations when using blood amino acid enrichment as the precursor pool (258.8)

The amino acid enrichment in blood (E b ) is often used in clinically relevant stable isotope studies to calculate muscle protein fractional synthesis rates (FSR), but it underestimates the FSR compared to methods using intracellular enrichment in muscle (E i ). We compared the FSR calculated with intravenous infusion of the novel tracer L‐[2,3,3,4,5,5,5,6,6,6‐ 2 H 10 ]leucine ([ 2 H 10 ]leu) to infusion of the traditional tracer L‐[ 13 C 6 ]phenylalanine ([ 13 C 6 ]phe) using E b and E i . Because [ 2 H 10 ]leu is intracellularly metabolized to [ 2 H 9 ]leu prior to reentry into the blood, we hypothesize that using [ 2 H 10 ]leu will minimize the discrepancy between FSR values calculated using E b or E i compared to [ 13 C 6 ]phe‐calculated FSR values using the corresponding E b or E i . To test our hypothesis, six healthy subjects received simultaneous infusions of the two stable‐isotope tracers following standard protocols. The [ 2 H 9 ]leu‐calculated FSR (%h ‐1 ) was 0.08±0.01 based on E b and 0.18±0.01 based on E i . The corresponding [ 13 C 6 ]phe‐calculated FSR values were 0.06±0.01 and 0.25±0.02, respectively. Moreover, the difference in the [ 2 H 9 ]leu‐calculated FSR values using E i vs E b was significantly less ( P <0.01; 0.10±0.01) compared to the difference in the corresponding [ 13 C 6 ]phe‐calculated FSR values (0.19±0.02). We conclude that, compared to [ 13 C 6 ]phe, the [ 2 H 10 ]leu tracer offers a more accurate approach to calculating FSR when E b is sought as an alternative to the E i.Grant Funding Source : Supported by NIH/NIDDK Grant# R01 DK094062; NCATS Grant# UL1 TR000135