Efficiency of substitution of 2-ketoisocaproic acid and 2-ketoisovaleric acid in the diet of normal and uremic growing rats

Effects ofvarious intakes ofthe ketoanalogues ofleucine(KICA)and valine (K! VA) on growth, nitrogen, and urea excretion were examined and compared to those ofan optimal intake (A) of the corresponding amino acids. Diet KICA and KIVA contents varied from 1 to 4 times A. In controls, growth was significantly reduced with eqwmolar substitution, corrected with twice A, and unchangedat higher levels. Doubling KICA corrected growth except with substantial anorexia. In uremic rats fed KIVA, growth was corrected at twice A. Low-KICA diets reduced plasma-leucine level; higher KICA diets normalized plasmaleucine and revealed branched-chain amino acid (BCAA) antagonism. Changes in 2-ketoacids were unrelated to those of BCAA. In uremia, KICA decreased plasma and urinary urea without changing nitrogen retention. Ketoacid substitution for amino acids was 50% efficient in normal rats and not altered by uremia. BCKAs, specifically KICA, could modify urea metabolism. Am I C/in Nuir l986;44:832-46.