Ornithine alpha-ketoglutarate metabolism in the healthy rat in the postabsorptive state.
To gain further insight into the ability of ornithine alpha-ketoglutarate (OKG) to generate key metabolites, the aim of this work was to study the short-term metabolism, that is, 1 hour after administration, of OKG in plasma and tissues. Particular attention was paid to keto acids (alpha-ketoglutarate and branched-chain keto acids). Young (3 weeks old) male Wistar rats in the postabsorptive state received either 1.5 g/kg of monohydrated OKG (OKG group, n = 8) diluted in distilled water or an equivalent volume of saline solution at 0.9% (control group, n = 8) by gavage and were killed 1 hour later. Plasma, liver, jejunal and ileal mucosa, and the extensor digitorum longus muscle were removed to analyze amino and keto acid contents. Major metabolites detected after OKG ingestion (ornithine [ORN], alpha-ketoglutarate, proline and glutamate; OKG vs control, P < .05) and the absence of increased arginine (and even a decrease in jejunum and muscle) and citrulline levels suggested that ORN was mainly metabolized by the ORN aminotransferase pathway. In addition, significantly decreased plasma branched-chain keto acids and increased hepatic branched-chain amino acids (OKG vs control, P < .05) were observed upon OKG ingestion. Finally, glutamine accumulation restricted to the intestine, as evidenced in this short-term study, suggests that the effects of OKG on glutamine pools in other tissues in various pathological states after several days of treatment, as observed in previous studies, may be related to a long-term induction of glutamine synthetase.
Loï
Cécile
C
Faculté de Pharmacie, Laboratoire de Biologie de la Nutrition, EA 2498, Paris Descartes University, 75270 Paris Cedex 6, France. cecile.loi@nutrition-paris5.org
Nakib
Samir
S
Neveux
Nathalie
N
Arnaud-Battandier
Franck
F
Cynober
Luc
L
D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007651:Keto Acids / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D011392:Proline / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000597:Amino Acids, Branched-Chain; D007651:Keto Acids; D007656:Ketoglutaric Acids; D002956:Citrulline; D018698:Glutamic Acid; C002118:ornithine alpha-ketoglutarate; D001120:Arginine; D011392:Proline; D009952:Ornithine