Measurement of L-[1-¹⁴C]Leucine Kinetics in Splanchnic and Leg Tissues In Humans: Effect of Amino Acid Infusion

Although whole-body leucine flux is widely measured to study body protein turnover in humans, the contribution of specific tissues to the total-body measurement remains unknown. By combining the organ-balance technique with the systemic infusion of L-[1-¹⁴C]leucine, we quantitated leucine production and disposal by splanchnic and leg tissues and by the whole body, simultaneously, in six normal men before and during amino acid infusion. At steady state, disposal of arterial leucine by splanchnic and leg tissues was calculated from the percent extraction (E) of L-[1-¹⁴C]leucine counts: uptake = E × [Leu]_a × flow. Tissue release of cold leucine (from protein turnover) into vein was calculated as the difference between leucine uptake and the net tissue leucine balance. In the postabsorptive state, despite substantial (P < .01) extraction of L-[1-¹⁴C]leucine by splanchnic (23 ± 1%) and leg (18 ± 2%) tissues, net leucine balance across both tissue beds was small, indicating active simultaneous disposal and production of leucine at nearly equivalent rates. Splanchnic tissues accounted for −50% of the measured total-body leucine flux. During amino acid infusion, the net leucine balance across splanchnic and leg tissues became positive, reflecting not only an increase in leucine uptake but also a marked suppression (by ∼50%, P < .02) of cold leucine release. This reduction in splanchnic and leg leucine release was indicated by a sharp decline in whole-body endogenous leucine flux. Conclusions: 1) combining the organ-balance method with systemic L-[1-¹⁴C]leucine infusion enables leucine kinetics to be measured simultaneously in the whole body and in specific tissues; 2) splanchnic tissues account for −50% of whole-body leucine flux in postabsorptive humans; and 3) amino acid infusion markedly suppresses leg and splanchnic tissue leucine release, which may indicate inhibition of proteolysis.