Does the ornithine–α-ketoglutarate ratio influence ornithine α-ketoglutarate metabolism in healthy rats?

Loi, Camilla; Hamani, Djamel; Moinard, Christophe; Bishoff, Laurent; Neveux, N.; Garbay, Christiane; Cynober, Luc

doi:10.1016/j.metabol.2006.09.004

Cited by 4 publications

References 18 publications

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Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production

et al. 2009

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The aim of this study was to determine the effects of alpha-ketoglutarate on neutrophil (PMN), free alpha-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] and released myeloperoxidase (MPO) activity. Exogenous alpha-ketoglutarate significantly increased PMN alpha-ketoglutarate, pyruvate, asparagine, glutamine, asparatate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Additionally, in parallel with intracellular alpha-ketoglutarate changes, increases in O(2) (-) formation, H(2)O(2)-generation and MPO activity have also been observed. We therefore believe that alpha-ketoglutarate is important for affecting PMN "susceptible free amino- and alpha-keto acid pools" although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic alpha-ketoglutarate levels are relevant metabolic determinants in PMN nutrition considerably influencing and modulating the magnitude and quality of the granulocytic host defense capability as well as production of ROS.

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Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production

et al. 2009

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Effects of ornithine α-ketoglutarate on growth performance and gut microbiota in a chronic oxidative stress pig model induced byd-galactose

Wang

Yin

et al. 2020

Food Funct.

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Pharmacokinetics of Arginine and Related Amino Acids

Cynober

2007

The Journal of Nutrition

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Arginine (ARG) and its related amino acids (AAs) ornithine (ORN) and citrulline (CIT) find a range of applications as dietary supplements in subgroups of healthy subjects (e.g., bodybuilders) and patients with acute or chronic malnutrition. These AAs appear to be well utilized in humans with, in general, a rapid return of blood concentrations to basal values (i.e., within 5-8 h) and low absolute and relative excretion in urine (<5% of administered dose). Based on published data for the maximum observed plasma concentrations (Cmax) after administration of doses in the range 5 to 10 g, CIT appeared to present relatively better absorption and systemic bioavailability than ARG and ORN. The few relevant dose-ranging studies available include 1 limited to a single subject receiving 5- to 20-g doses of ornithine alpha-ketoglutarate and another in which 8 subjects received from 5 to 15 g of CIT. Comparison of these 2 studies further indicates that CIT has higher bioavailability than ORN. The pharmacokinetics and metabolism of these AAs are modified by the coadministration of a salt such as alpha-ketoglutarate that modifies AA metabolism, as has clearly been demonstrated for ornithine alpha-ketoglutarate. Concomitant administration of a meal leads to a 15- to 30-min delay in Cmax. Finally, data from various pharmacokinetic studies together with basic physiology and biochemistry indicate that ARG is a net urea producer and ORN has a nitrogen-sparing effect, whereas CIT is neutral. However, most of the studies performed to date carry methodological weaknesses and are difficult to compare because of a number of confounding factors. To date, there have been no pharmacokinetic studies on the long-term administration of these AAs in healthy subjects despite the need to determine the safe upper limit of daily intake.

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Does the ornithine–α-ketoglutarate ratio influence ornithine α-ketoglutarate metabolism in healthy rats?

Cited by 4 publications

References 18 publications

Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production

Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production

Effects of ornithine α-ketoglutarate on growth performance and gut microbiota in a chronic oxidative stress pig model induced byd-galactose

Pharmacokinetics of Arginine and Related Amino Acids

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