AlphaKetoglutarate

Alpha-ketoglutarate, also known as α-ketoglutaric acid, is a five-carbon dicarboxylic alpha-keto acid that serves as a central intermediate in cellular metabolism. In the mitochondrion, it is formed from isocitrate and is then converted to succinyl-CoA by the α-ketoglutarate dehydrogenase complex, producing NADH and CO2 in the process. Through this position in the tricarboxylic acid cycle, α-KG participates in energy production and de novo biosynthesis of both carbohydrates and amino acids.

Beyond its role in energy metabolism, α-KG acts as an amino group acceptor in transamination reactions, forming glutamate, which can be further converted to glutamine or other amino acids. As a nitrogen sink, it helps regulate nitrogen balance in cells and tissues. It can be replenished by anaplerotic reactions, ensuring continued flux through the TCA cycle.

Dietary and medical use: Exogenous α-KG is sold as a dietary supplement, frequently as calcium α-ketoglutarate or other salts. It is used in sports nutrition and in some medical nutrition formulations to support nitrogen balance or gut and wound healing; however, robust clinical evidence for improvements in muscle performance or health outcomes is limited and inconsistent.

Safety: When used at recommended doses, α-KG is generally well tolerated, but high doses can cause gastrointestinal upset. People with kidney disease or those taking certain medications should use caution and consult a healthcare professional.