How does alpha-ketoglutarate work?

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    Last Updated: May 16, 2025

    Alpha-ketoglutarate (AKG) serves as a precursor to amino acids and aids in the formation of glutamine and glutamate, which are vital for energy and recovery in certain cells. Additionally, AKG regulates gene expression, influences cell signaling related to aging, and exhibits antioxidant properties by reducing reactive oxygen species and enhancing enzyme activity.

    AKG is helpful as a precursor to amino acids. It reacts with ammonia in the body to form glutamine and other amino acids. Glutamine in turn is an important source of energy for lymphocytes and enterocytes (a type of white blood cell and intestinal cells, respectively), and can be used by the body to recover from trauma. This reaction with ammonia also forms glutamate, which helps increase proline production, which is important for collagen production.[1][2]

    AKG is also a regulator of gene expression, and works on cell signaling pathways that are involved in the aging process. It might extend lifespan by limiting the activity of ATP synthase, an energy carrier for cellular energy metabolism. AKG also inhibits target of rapamycin (TOR) and its mammalian equivalent, mammalian/mechanistic target of rapamycin (mTOR), which are protein kinases that regulate cell growth and metabolism across several kingdoms of life. Inhibiting ATP synthase and TOR/mTOR seems to prolong life as demonstrated in worms, mice, and flies.[2][3][1] AKG also shows some antioxidant activity, both in eliminating reactive oxygen species (ROS) and by improving the activity of other enzymes that do so, such as superoxide dismutase (SOD).[4][5]