Optimal dietary substitution of racemic ketoanalogues for isoleucine in growing normal and uremic rats.

Dietary ketoanalogues (KAs) were shown to replace their essential amino acids with a 50% efficiency for valine and leucine. We determined the optimal concentration of the racemic KA of isoleucine (KMVA) in uremic and control rats: nutrition responses were compared between a diet containing optimal isoleucine concentration and diets containing various KMVA concentrations. Isomolar replacement of isoleucine produced anorexia, stunting, and poor nitrogen balance. Doubling KMVA partially improved these indices. Tripling KMVA lessened urea production and improved growth up to that obtained with the isoleucine diet in uremic but not in control rats (20% lower). A further KMVA increase produced no further benefit. Among plasma branched-chain amino acids, only alloisoleucine was affected; it increased with increasing KMVA concentration, being maximum after tripling KMVA. Racemic KMVA could replace isoleucine with a 35% efficiency but supported no growth acceleration in uremic rats and no maximal growth in control rats. Plasma alloisoleucine rose without adverse nutrition effects.