[Frontiers in Bioscience 16, 1186-1196, January 1, 2011]

Alpha-Ketoglutarate and intestinal function

Yongqing Hou1, Lei Wang1, Binying Ding1, Yulan Liu1, Huiling Zhu1, Jian Liu1, Yongtang Li1, Ping Kang1,Yulong Yin2, Guoyao Wu3,4

1Hubei key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China, Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha 410125, China, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China 100193,4Department of Animal Science, Texas A&M University, College Station, TX 77843 USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Growth performance
4. α-Ketoglutarate and gut function
4.1. Intestinal morphology
4.2. Absorptive and barrier function
4.3. antioxidative capacity
4.4. Concentrations of amino acids and protein in jejunal mucosa
4.5. Concentrations of ATP, ADP, and AMP in the intestinal mucosa
4.6. Concentrations of nitric oxide (NO) and nitric oxide synthase (NOS) in the intestinal mucosa
4.7. Heat shock protein 70 (HSP70) expression
4.8. Phosphorylation levels for mammalian target of rapamycin(mTOR)
4.9. Phosphorylation levels for adenosine monophosphate (AMP)-activated protein kinase(AMPK) and acetyl-CoA carboxylase(ACC)
5. Summary and perspective
6. Acknowledgements
7. References

1. ABSTRACT

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.