Enteral administration of ornithine alpha-ketoglutarate or arginine alpha-ketoglutarate: A comparative study of their effects on glutamine pools in burn-injured rats

Objectives: Ornithine alpha-ketoglutarate has proved to be an efficient nutritional support in trauma situations, especially after burn injury. To determine whether the action of ornithine alpha-ketoglutarate is due to its alpha-ketoglutarate moiety (as a glutamine precursor), we studied the effects of alpha-ketoglutarate administered to rats as ornithine alpha-ketoglutarate, or in combination with arginine salt (arginine alpha-ketoglutarate), as the two closely related amino acids have similar metabolic behavior. Design: Prospective, randomized trial. Setting: Animal laboratory. Subjects: Forty-six male Wistar rats, weighing similar to 90 g. Interventions: Rats were burned over 20% of their body surface area, starved for 24 hrs, with water ad libitum, and then enterally refed for 48 hrs using Osmolite(R)(210 kcal/kg/day, 1.2 g of nitrogen/kg/day), supplemented with one of the following: a) an amount of glycine isonitrogenous to ornithine alpha-ketoglutarate (group 1) b) 5 g of monohydrated ornithine alpha-ketoglutarate/kg/day (group 2); c) an amount of arginine alpha-ketoglutarate isonitrogenous to ornithine alpha-ketoglutarate (group 3); or d) an amount of arginine alpha-ketoglutarate isomolar to ornithine alpha-ketoglutarate (group 4). Measurements and Main Results: We measured amino acid concentrations in plasma, muscle, and river, and plasma urea concentration. At refeeding, ornithine alpha-ketoglutarate increased plasma glutamine concentration (p<.05 vs. the three other groups), and counteracted the increase in plasma phenylalanine concentration. In muscle, although the three alpha-ketoglutarate combinations induced similar increases in the glutamate pool, ornithine alpha-ketoglutarate induced the highest increase in glutamine (7.0 +/- 0.3 vs. 5.4 +/- 0.3 mu mol/g in group 3, 6.3 +/- 0.3 in group 4, and 4.6 +/- 0.2 in group 1, p<.01 between group 2 and groups 3 or 1). Also, only ornithine alpha-ketoglutarate increased liver glutamine concentration. Finally, isomolar arginine alpha-ketoglutarate increased plasma urea concentration (+50% vs, the three other groups, p<.01). Conclusions: Our results demonstrate, for the first time, the following: a) the action of ornithine alpha-ketoglutarate as a glutamine precursor cannot solely be ascribed to alpha-ketoglutarate since arginine nine alpha-ketoglutarate combinations did not exhibit this effect to the same extent; and b) the action of ornithine alpha-ketoglutarate is not due to its nitrogen content since isonitrogenous arginine alpha-ketoglutarate did not reproduce the effects of ornithine alpha-ketoglutarate.