Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.
Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.
Cynober
L
L
Laboratoire de Biochimie A, Hôpital Saint Antoine, Paris, France.
Coudray-Lucas
C
C
de Bandt
J P
JP
Guéchot
J
J
Aussel
C
C
Salvucci
M
M
Giboudeau
J
J
D000284:Administration, Oral; D000328:Adult; D000596:Amino Acids / Q000097:blood*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007656:Ketoglutaric Acids / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009952:Ornithine / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values
D000596:Amino Acids; D007328:Insulin; D007656:Ketoglutaric Acids; D005934:Glucagon; D009952:Ornithine