L-kynurenine catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of L-kynurenine, the L-enantiomer of the amino acid kynurenine (3-(2-aminobenzoyl)-alanine). [GOC:yaf]

L-kynurenine catabolism is a critical metabolic pathway that primarily occurs in the liver and involves the breakdown of L-kynurenine, an amino acid derived from tryptophan. This pathway is closely linked to various physiological processes, including immune responses, inflammation, neurotransmission, and oxidative stress.

The initial step in L-kynurenine catabolism is catalyzed by the enzyme kynurenine aminotransferase (KAT), which converts L-kynurenine into kynurenic acid (KYNA) or 3-hydroxykynurenine (3-HK).

* The KYNA branch is considered a detoxifying pathway, as KYNA is a potent antagonist of the NMDA receptor, a key player in neuronal excitability.

* The 3-HK branch, on the other hand, is primarily involved in the production of quinolinic acid (QUIN), a potent agonist of the NMDA receptor. This branch is highly reactive and can lead to oxidative stress, inflammation, and neurotoxicity.

Further down the 3-HK branch, 3-HK is converted to 3-hydroxyanthranilic acid (3-HAA) by kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme in this pathway. 3-HAA is then transformed into QUIN by 3-hydroxyanthranilate 3,4-dioxygenase (HAAO).

The balance between the KYNA and 3-HK branches significantly influences the overall outcome of L-kynurenine catabolism. A shift towards the 3-HK branch has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and schizophrenia.

L-kynurenine catabolism is also tightly regulated by various factors, including inflammation, oxidative stress, and nutritional status. For instance, during inflammatory conditions, the activity of KMO is often increased, leading to increased QUIN production and exacerbation of inflammation.

In conclusion, L-kynurenine catabolism is a complex and dynamic process with far-reaching implications for health and disease. Understanding the intricate mechanisms of this pathway is crucial for developing novel therapeutic strategies for a range of disorders associated with imbalances in L-kynurenine metabolism.'
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Proteins (3)

Compounds (6)