Coadministration of ornithine and α-ketoglutarate is no more effective than ornithine alone as an arginine precursor in piglets enterally fed an arginine-deficient diet

Simultaneous administration of α-ketoglutarate and ornithine, in a 1:2 molar ratio, may improve the effectiveness of ornithine as an arginine precursor in neonatal piglets by shifting ornithine metabolism away from oxidation and toward the synthesis of arginine and other metabolically important compounds. To study this proposed mechanism, enterally fed piglets were allocated to receive 1 of 4 diets for 5 d: an arginine-deficient [1.2 mmol/(kg · d) arginine] diet (basal), or the basal diet supplemented with either α-ketoglutarate [4.6 mmol/(kg · d)] (+α-KG), ornithine [9.2 mmol/(kg · d)] (+Orn), or both ornithine and α-ketoglutarate (+α-KG/+Orn, molar ratio 1:2). Primed, constant infusions of [1- ¹⁴C]ornithine given both intragastrically and intraportally were used to measure ornithine kinetics and determine the role of first-pass intestinal metabolism in ornithine metabolism. Whole body arginine and glutamate kinetics were measured using a primed, constant intragastric infusion of [guanido- ¹⁴C]arginine and [3,4-³H]glutamate. The diets did not affect plasma arginine or ammonia concentrations, arginine flux, or arginine synthesis from ornithine. Therefore, arginine synthesis was not increased by the simultaneous infusion of ornithine and α-ketoglutarate. Piglets that received dietary ornithine had a 2-fold greater rate of proline synthesis from ornithine (P<0.05) and oxidized a greater (P<0.05) portion of the infused ornithine than piglets in the basal and +α-KG groups. Overall, ornithine addition to an arginine deficient diet had a greater effect on ornithine and arginine metabolism than the addition of α-ketoglutarate. First-pass intestinal metabolism was critical for ornithine synthesis and conversion to other metabolites but not for ornithine oxidation.