Alpha-ketoglutarate, a key molecule involved in nitrogen circulation in both animals and plants, in the context of human gut microbiota and protein metabolism

Abstract

Purpose: Nitrogen (N₂) is an indispensable metabolite required for the synthesis of protein. In animals, gut bacteria and, to a certain extent, even hepatocytes, are able to assimilate nitrogen from ammonium (NH₄⁺), which is essentially derived from the amine group (-NH₂) and which is at the same time a very toxic metabolite. Initially, NH₄⁺ is coupled to alpha-ketoglutarate (AKG), a reaction which results in the appearance of glutamate (one amine group), and after that, in the appearance of glutamine - containing two amine groups. The surplus of NH₄⁺ which is not utilized by AKG/glutamate/glutamine is eliminated as urea in the urine, via the urea cycle in hepatocytes. Plants bacteria also assimilate nitrogen from NH₄⁺, by its fixation to ammonia (NH₃)/NH₄⁺.

Materials/methods: Previous studies have shown that AKG (also known as 2-oxo-glutaric acid or 2-oxopentanedioic acid), the primary metabolite of Rhizobium and gut bacteria, is essential for the assimilation of nitrogen.

Results: Symbiotic bacteria produce AKG, which together with glutamate dehydrogenase (GDH), 'generates' primarily amine groups from NH₄⁺. The final product is glutamate - the first amino acid. Glutamate has the capacity to be converted to glutamine, through the action of glutamine synthetase, after the assimilation of the second nitrogen from NH₄⁺.

Conclusion: Glutamate/glutamine, derivatives of AKG metabolism, are capable of donating amine groups for the creation of other amino acids, following NH₂ transamination to certain metabolites e.g., short chain fatty acids (SCFA).

Keywords: Amino acids; E. coli; Gastrointestinal tract; Nitrogen fixation; Rhizobium.