Splanchnic bed utilization of enteral alpha-ketoisocaproate in humans

The branched-chain ketoacids (BCKAs) are used as dietary supplements to spare essential amino acid nitrogen, yet little is known about their absorption and utilization in the body. To study the fate of enterally delivered alpha-ketoisocaproate (KIC), seven healthy adults were infused in the postabsorptive state with [1-(13)C]KIC and [phenyl-2H5]phenylalanine intravenously (NGI) and with [5,5,5-2H3]KIC by nasogastric tube (NG). After 3.5 hours, the routes of tracer infusion were switched for an additional 3.5 hours. Each subject received a second infusion study on a different day with the order of tracer infusion reversed. KIC and phenylalanine kinetics and first-pass uptake and disposal of the enteral tracer by the splanchnic bed were calculated from the tracer enrichments measured in plasma KIC, leucine, and phenylalanine and breath CO2. Phenylalanine flux was 39.5 +/- 1.2 micromol/kg/h during the i.v. infusion periods. KIC flux was 33.1 +/- 1.8 and 30.4 +/- 1.4 micromol/kg/h measured with 13C- and 2H3-KIC, respectively, and these values were significantly different. The fraction of enterally delivered tracer sequestered by the splanchnic bed on the first pass was 30.9% +/- 2.0%, 30.0% +/- 1.4%, and 30.7% +/- 2.7% for 13C-KIC, 2H3-KIC, and 2H5-phenylalanine, respectively. The fraction of infused 13C-KIC tracer recovered as 13CO2 was 27.1% +/- 1.2% and 24.0% +/- 0.9% during i.v. and NG infusion, respectively. From these data, the fraction of ng KIC tracer extracted and oxidized on the first pass was calculated to be 5.1% +/- 1.1%. This fraction was greater than that previously reported for leucine extraction and oxidation (2%), but it was still only a small fraction of the overall extraction (5/30 = 16%). Because the only two fates of the KIC tracer extracted by the splanchnic bed are oxidation or transamination to leucine, the majority (84%) of the KIC tracer was extracted and converted to leucine. These results demonstrate that KIC delivered enterally to postabsorptive humans is rapidly extracted and predominantly converted to leucine by the splanchnic bed. This leucine appears to be available for use by both the splanchnic bed and the whole body.