Recovery of13CO2from infused [1-13C]leucine and [1,2-13C2]leucine in healthy humans

Carbon (C) in the 1-position of leucine is released as CO2with the decarboxylation of α-ketoisocaproate (KIC). Carbon in the 2-position of leucine undergoes several additional metabolic steps before entering the tricarboxylic acid (TCA) cycle in the 1-position of acetyl-CoA, where it can be released as CO2or be incorporated into other compounds. This study examined the metabolic fate of C in the 2-position of leucine. We infused 11 healthy subjects with [1-13C]leucine and [1,2-13C2]leucine for 3.5–4 h to measure leucine kinetics and the oxidation of the tracers from enrichments of13C in blood and expired CO2. The fraction of leucine infused that was oxidized (fox) was used to define the degree of recovery of the13C label(s) for each tracer. As expected, leucine appearance (means ± SE) did not differ between tracers (13C1: 92.1 ± 3.1 vs.13C2: 89.2 ± 3.2 μmol · kg−1· h−1) when calculated using plasma leucine enrichments as an index of intracellular enrichment. A small (3%) but significant ( P = 0.048) difference between tracers was found when KIC was used to calculate leucine appearance (13C1: 118.0 ± 4.1 vs.13C2: 114.4 ± 4.5 μmol · kg−1· h−1). The value of foxwas 14 ± 1% for [1,2-13C2]leucine and was lower than the foxfor [1-13C]leucine (19 ± 1%). From the foxdata, we calculated that the recovery of the 2-13C label in breath CO2was 58 ± 6% relative to the 1-13C label. These findings show that, although a majority of the 2-13C label of leucine is recovered in breath CO2, a significant percentage (∼42%) is retained in the body, presumably by transfer to other compounds, via TCA exchange reactions.