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)

Abstract

The amino acid enrichment in blood (Eb) 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 (Ei). We compared the FSR calculated with intravenous infusion of the novel tracer L‐[2,3,3,4,5,5,5,6,6,6‐2H10]leucine ([2H10]leu) to infusion of the traditional tracer L‐[13C6]phenylalanine ([13C6]phe) using Eb and Ei. Because [2H10]leu is intracellularly metabolized to [2H9]leu prior to reentry into the blood, we hypothesize that using [2H10]leu will minimize the discrepancy between FSR values calculated using Eb or Ei compared to [13C6]phe‐calculated FSR values using the corresponding Eb or Ei. To test our hypothesis, six healthy subjects received simultaneous infusions of the two stable‐isotope tracers following standard protocols. The [2H9]leu‐calculated FSR (%h‐1) was 0.08±0.01 based on Eb and 0.18±0.01 based on Ei. The corresponding [13C6]phe‐calculated FSR values were 0.06±0.01 and 0.25±0.02, respectively. Moreover, the difference in the [2H9]leu‐calculated FSR values using Ei vs Eb was significantly less (P<0.01; 0.10±0.01) compared to the difference in the corresponding [13C6]phe‐calculated FSR values (0.19±0.02). We conclude that, compared to [13C6]phe, the [2H10]leu tracer offers a more accurate approach to calculating FSR when Eb is sought as an alternative to the Ei. Grant Funding Source: Supported by NIH/NIDDK Grant# R01 DK094062; NCATS Grant# UL1 TR000135