Alpha-Ketoglutarate and intestinal function

Front Biosci (Landmark Ed). 2011 Jan 1;16:1186-96. doi: 10.2741/3783.


Alpha-ketoglutarate (AKG) is an intermediate of the Krebs cycle which bridges amino acid metabolism with glucose oxidation in animals. Of particular interest is the conversion of AKG into glutamate by mitochondrial glutamate dehydrogenase in the gastrointestinal tract where glutamate has multiple physiological functions (including regulation of cell function, neurotransmission, and gastric emptying). Additionally, AKG stimulates the initiation of catabolism of branched-chain amino acids (BCAA) via BCAA transaminase in enterocytes. Oxidation of AKG also provides large amounts of ATP and modulates cellular redox state in the small intestine. Translating the basic research into practice, results of recent studies indicate that dietary supplementation with AKG alleviates oxidative stress and injury in intestinal mucosal cells, while improving intestinal mucosal integrity and absorption of nutrients in endotoxin-challenged pigs. The beneficial effects of AKG are associated with increased activation of the mTOR signaling pathway and net protein synthesis. Thus, AKG is a novel and promising supplement in diets to improve intestinal health in animals and possibly humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Acetyl-CoA Carboxylase / metabolism
  • Amino Acids, Branched-Chain / metabolism
  • Animals
  • Dietary Supplements
  • Glutamic Acid / metabolism
  • HSP70 Heat-Shock Proteins / biosynthesis
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestine, Small / physiology*
  • Ketoglutaric Acids / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Phosphorylation
  • Swine
  • TOR Serine-Threonine Kinases / metabolism


  • Amino Acids, Branched-Chain
  • HSP70 Heat-Shock Proteins
  • Ketoglutaric Acids
  • Nitric Oxide
  • Glutamic Acid
  • Nitric Oxide Synthase
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase