Glutamine (Gln) is considered to be an important metabolic fuel for all rapidly dividing cells and can improve the synthesis of protein and inhibits protein catabolism in enterocytes. However, in the practical application, it is reported that Gln as a new feed additive, can be easily decomposed and expensive.

In order to solve this problem, researchers in the Institute of Subtropical Agriculture of the Chinese Academy of Sciences (ISA) found that alpha-ketoglutarate (AKG) as a precursor of Gln and glutamate, is more inexpensive, soluble, and stable than Gln, thus it would potentially replace Gln in swine production. Especially, AKG, which serves as a central intermediate of the tricarboxylic acid cycle, as well as the carbon skeleton for the synthesis of glutamate and glutamine(Gln), plays a key role in the oxidation of fatty acids, amino acids, and glucose.

To date, the mechanisms responsible for the action of AKG as Gln replacement on intestinal Gln metabolism in piglets remain unknown. Therefore, the present study was to determine the effects of AKG on intestinal Gln metabolism in vivo and in vitro. In vitro a total of twenty-one piglets were weaned at 28 days, and randomly divided into 3 different treatment groups. In vivo intestinal porcine epithelial cells-1 (IPEC-1) was incubated to investigate effects of 0.5, 2, and 3 mM AKG addition on Gln metabolism.

In the current study, researchers' results showed that compared with the Gln treatment, AKG could maintain the unremarkable growth performance of piglets under lower average daily feed intake condition. In comparison with the control group, the AKG and Gln groups exhibited an improvement in villus length, mucosal thickness, and crypt depth in the jejunum of piglets. And dietary AKG or Gln supplementation increased the utilization rate of serum free amino acids related to AKG and Gln metabolism and the mRNA expression of jejunal and ileal amino acid transporters.

Additionally, the in vitro study showed that the addition of 0.5, 2, and 3 mM AKG dose-dependently decreased the net utilization of Gln and formulation of ammonia, Glu, Ala, and Asp by intestinal porcine epithelial cells-1.

The team found that dietary AKG supplementation could improve Gln metabolism in piglet enterocytes and enhance the utilization of AA. "Alpha-ketoglutarate, as a replacement for Gln, could improve the growth performance and intestinal morphology of piglets," said HE Liuqin, a doctoral student at ISA. "The absorption of AA requires many transporter systems that differ with respect to their substrate specificity and driving force. AKG as a precursor of Gln and Glu may have a potent ´sparing´ effect on endogenous Gln pools, thus researchers found that the addition of AKG could affect Gln catabolism and the production of its metabolites in vivo."

This research was supported by National Basic Research Program of China (2013CB127301 and 2013CB127306), Hundred Talents Program of the Chinese Academy of Sciences, National Natural Science Fundation Project (31472106 and 31472107), National Science and Technology Support Project (2013BAD21B04).

The study entitled "Effects of Alpha-Ketoglutarate on Glutamine Metabolism in Piglet Enterocytes in Vivo and in Vitro" has been published in the journal of Agriculture and Food Chemistry, details could be found at http://www.ncbi.nlm.nih.gov/pubmed/27018713.