kynurenine metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving kynurenine, the amino acid 3-(2-aminobenzoyl)-alanine. [CHEBI:28683, GOC:mah, GOC:rph]

The kynurenine metabolic pathway is a key branch of tryptophan metabolism, initiating with the enzyme tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO). This pathway diverges from the conventional serotonin and melatonin synthesis route. TDO is primarily expressed in the liver, while IDO is expressed in various tissues, including immune cells.

The initial step involves the conversion of tryptophan to N-formylkynurenine by TDO or IDO. This intermediate is then rapidly hydrolyzed to kynurenine. Kynurenine is further metabolized via two main branches:

1. **Kynurenine pathway:** This branch involves a series of enzymatic reactions leading to the production of NAD+, a crucial coenzyme in numerous metabolic reactions. Key intermediates in this branch include:
* **Kynurenine**: This molecule is transported to the liver and other tissues, where it undergoes further metabolism.
* **3-Hydroxykynurenine**: This intermediate is produced from kynurenine by kynurenine 3-monooxygenase (KMO).
* **3-Hydroxyanthranilate**: This intermediate is produced from 3-hydroxykynurenine by kynureninase.
* **Quinolinate**: This molecule is produced from 3-hydroxyanthranilate by 3-hydroxyanthranilate 3,4-dioxygenase. Quinolinate is then converted to NAD+ by quinolinate phosphoribosyltransferase.

2. **Picolinate pathway:** This branch leads to the formation of picolinic acid, a potential neurotoxin. Key intermediates in this branch include:
* **Kynurenine**: Similar to the kynurenine pathway, kynurenine is the starting point for this branch.
* **Kynurenic acid**: This molecule is produced from kynurenine by kynurenine aminotransferase (KAT). Kynurenic acid is a potent NMDA receptor antagonist, potentially impacting neuronal excitability and neurotransmission.

The relative activity of these pathways is influenced by various factors, including genetic background, nutritional status, and inflammation. Dysregulation of the kynurenine pathway has been implicated in various diseases, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease), autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus), and cancer.

Therefore, the kynurenine metabolic pathway plays a significant role in diverse biological processes, ranging from NAD+ synthesis to neurotransmission, and its dysregulation can contribute to various pathological conditions.'
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Proteins (4)

Compounds (8)