Effect of ornithine alpha-ketoglutarate on glutamine pools in burn injury: evidence of component interaction.
BACKGROUND
Ornithine alpha-ketoglutarate (OKG) has proved to be efficient in restoring glutamine (Gln) pools which are strongly depleted in hypercatabolic patients. Since its two components, alpha-ketoglutarate (alphaKG) and ornithine (Orn), give rise to glutamate (Glu), they are both considered as Gln precursors. The aim of this study was to assess the relative contributions of Orn and alphaKG to Gln generation in a rat model of burn injury.


METHODS
Forty-eight young Wistar rats were scalded to give a 20% burn surface area. They were fasted for 24 h and then refed by enteral nutrition for 48 h by gavages with Osmolite (Abbott-Ross, 210 kcal/kg day(-1), 1.18 N/kg day(-1)) supplemented with either 5 g OKG/kg day(-1) (B-OKG), Orn (isomolar to OKG; B-Orn), alphaKG (isomolar to OKG; B-KG) or glycine (as an isonitrogenous control; B-Gly). Rats in the B-KG group also received glycine to make all the groups isonitrogenous. Amino acid concentrations were determined in plasma, muscles, jejunal mucosa and liver.


RESULTS
The alpha-KG-enriched diet had no effect on plasma Glu content or plasma and muscle Gln content compared with the burn-injured controls. The Orn-enriched diet significantly increased (p<0.01) muscle Glu and Gln contents but not plasma Gln content. In OKG-treated animals, plasma Gln as well as muscle Glu and Gln were significantly higher than in the control (p<0.01), alpha-KG-treated (p< 0.01) and Orn-treated (p<0.05 for muscle Gln and p<0.01 for plasma Gln) animals.


CONCLUSIONS
OKG was more efficient than Orn or alphaKG alone in restoring Gln pools in plasma and muscle, which is evidence of metabolic interaction between the two components of this molecule.
Cynober
L
L
Laboratoire de Biologie de la Nutrition EA2498, Faculté de Pharmacie, Université Paris Descartes, 4 av. De l'Observatoire, 75006, Paris, France. luc.cynober@htd.ap-hop-paris.fr
Lasnier
E
E
Le Boucher
J
J
Jardel
A
A
Coudray-Lucas
C
C
D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000628:therapy*; D004338:Drug Combinations; D004357:Drug Synergism; D004750:Enteral Nutrition; D005973:Glutamine / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000596:Amino Acids; D004338:Drug Combinations; D007656:Ketoglutaric Acids; D005973:Glutamine; C002118:ornithine alpha-ketoglutarate; D009952:Ornithine