Utilization for protein synthesis of leucine and valine compared with their keto analogues

Fasting rats were given [3H]leucine plus [14C]2-ketoisocaproate or [3H]valine plus [14C]2-ketoisovalerate, plus 33 micromol of each compound. The ratio of 14C to 3H (R) in protein 6 h after injection of these isotopes is a measure of the extent to which extracellular keto acid, as compared with extracellular amino acid, serves as the source of the intracellular amino acid used for protein synthesis. R for 2-ketoisocaproate (KIC) vs leucine was 0.45 +/- 0.03 for whole body protein after oral injection and 0.83 +/- 0.02 after iv injection. R values for 2-ketoisovalerate (KIV) vs valine were similar. R, measured in the protein of various organs and in albumin, fibrin, and globin, varied more than twofold. We conclude that at least half of KIC and KIV given orally in this dosage is oxidized in splanchnic organs during first pass but that, nevertheless, these keto acids given orally serve as significant sources of the intracellular amino acids used for protein synthesis in most organs, particularly brain and heart.