Nitrogen sparing by 2-ketoisocaproate in parenterally fed rats

In rats receiving total parenteral nutrition with or without sodium 2-ketoisocaproate (KIC; 2.48 g.kg-1.day-1), L-[1-13C]leucine and [1-14C]KIC were constantly infused for 6 h. CO2 production, 14CO2 production, 13CO2 enrichment, urinary urea nitrogen (N) plus ammonia N and total urinary N were measured. Whole body protein synthesis (S) was calculated in non-KIC-infused rats and also in unfed rats infused with [1-14C]leucine from fractional oxidation of labeled leucine (1-F), where F is fractional utilization for protein synthesis, and urea N plus ammonia N excretion (C) as S = C x F/(1-F). Addition of KIC caused a significant reduction in N excretion and a significant improvement in N balance. Fractional oxidation of labeled KIC increased, whereas fractional utilization of labeled KIC for protein synthesis decreased, but the extent of incorporation of infused KIC into newly synthesized protein (as leucine) amounted to at least 40% of the total rate of leucine incorporation into newly synthesized whole body protein. We conclude that addition of KIC spares N in parenterally fed rats and becomes a major source of leucine for protein synthesis.