Infusion of labeled KIC is more accurate than labeled leucine to determine human muscle protein synthesis

The leucine constant infusion method is the most commonly used method for measuring fractional synthetic rates (FSR) of muscle protein. However, this method has been criticized because of the uncertainty involved in measuring precursor pool enrichment. We present an alternative method for measuring muscle FSR by giving a constant infusion of α-[1-¹³C]ketoisocaproate (α- [1-¹³C]KIC). We infused α-[1-¹³C]KIC and [5,5,5-²H₃]leucine for 4 h in five volunteers and took plasma samples half-hourly and muscle biopsies at 1 and 4 h of isotope infusion. When KIC was infused, intramuscular free leucine enrichment was the same as arterial leucine enrichment. However, when labeled leucine was infused, intramuscular free leucine enrichment was only 76 ± 3% of arterial KIC enrichment, which agrees with previous reports that plasma KIC enrichment does not accurately reflect intramuscular leucine enrichment. We obtained an FSR of 2.25 ± 0.12%/day by use of this method, which agrees with a previous report using tRNA bound leucine as the precursor. In conclusion, the KIC infusion method overcomes the theoretical limitations of the leucine infusion.