2-oxoglutarate metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving oxoglutarate, the dianion of 2-oxoglutaric acid. It is a key constituent of the TCA cycle and a key intermediate in amino-acid metabolism. [ISBN:0198506732]

The 2-oxoglutarate metabolic process encompasses a series of biochemical reactions involved in the production, utilization, and degradation of 2-oxoglutarate, a key intermediate in the citric acid cycle and a central metabolite in various metabolic pathways.

2-oxoglutarate is produced in the mitochondria through the oxidative decarboxylation of isocitrate by the enzyme isocitrate dehydrogenase. It then serves as a substrate for the enzyme α-ketoglutarate dehydrogenase, which catalyzes its oxidative decarboxylation to succinyl-CoA, generating NADH and releasing carbon dioxide. This reaction is an essential step in the citric acid cycle, linking carbohydrate metabolism to the electron transport chain and ATP production.

Beyond its role in the citric acid cycle, 2-oxoglutarate plays a pivotal role in various metabolic processes, including:

- **Gluconeogenesis:** 2-oxoglutarate can be converted to glucose via the gluconeogenic pathway, providing an alternative source of glucose when carbohydrate stores are depleted.
- **Amino acid metabolism:** 2-oxoglutarate serves as an acceptor of amino groups in the transamination reactions that interconvert amino acids.
- **Nitrogen assimilation:** 2-oxoglutarate is involved in the incorporation of ammonia into organic molecules, a process crucial for nitrogen fixation and protein synthesis.
- **Synthesis of heme:** 2-oxoglutarate is required for the biosynthesis of heme, a key component of hemoglobin and other heme-containing proteins.
- **Regulation of gene expression:** 2-oxoglutarate acts as a co-substrate for certain dioxygenases, enzymes involved in the modification of DNA and histone proteins, influencing gene expression.

The metabolic fate of 2-oxoglutarate is tightly regulated by various enzymes and factors, ensuring its appropriate levels within the cell and its optimal utilization in different metabolic pathways. Disruptions in 2-oxoglutarate metabolism can lead to various metabolic disorders, including mitochondrial dysfunction, metabolic acidosis, and neurodevelopmental disorders.'
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Proteins (5)

Compounds (21)