Alpha-ketoglutarate (2-oxoglutarate)

Central intermediate of the citric acid cycle – a junction point for amino acid and energy metabolism. AKG is also a cofactor of epigenetic demethylating enzymes (TET).

What alpha-ketoglutarate does in the body

In the citric acid cycle, alpha-ketoglutarate (AKG) is formed when isocitrate dehydrogenase converts isocitrate; CO₂ and NADH are released in the process. Alpha-ketoglutarate dehydrogenase then breaks AKG down into succinyl-CoA – an enzyme complex that, like pyruvate dehydrogenase, needs vitamin B1, lipoic acid, vitamin B2, niacin and pantothenic acid. AKG is also the hub to amino acid metabolism: it takes up amino groups and so becomes glutamate, from which glutamine, the messenger GABA and glutathione are made; conversely, glutamate flows into the cycle as AKG. In addition, numerous enzymes need AKG as a helper, including the TET enzymes, which remove methyl groups from DNA, and – together with vitamin C and iron – the enzymes that stabilise collagen.

Low alpha-ketoglutarate – what happens in the body?

When little AKG is present, the citric acid cycle turns more slowly and fewer electrons are available to the respiratory chain. At the same time, starting material is lacking to capture nitrogen from protein breakdown as glutamate and pass it on to the urea cycle. AKG is used up more when a lot of glutamate and glutamine has to be made – for example with high protein turnover or a high demand for glutathione. The AKG-dependent enzymes then also work more slowly, including in the stabilisation of collagen.

High alpha-ketoglutarate – what happens in the body?

A raised value usually shows that AKG is being processed into succinyl-CoA more slowly. Alpha-ketoglutarate dehydrogenase is sensitive: with a lack of vitamin B1, lipoic acid, vitamin B2, niacin or pantothenic acid it works more slowly, and oxidative stress also inhibits it. AKG then builds up, and the following steps of the cycle – succinate, fumarate and malate as well as the supply of NADH to the respiratory chain – receive less supply. More AKG is also produced when many amino acids are broken down, for example with a very high-protein diet.

The interpretation is given in your report.