kynurenine pathway

The kynurenine pathway is the primary metabolic route for breaking down tryptophan in the body. It converts tryptophan (an essential amino acid) into kynurenine and its metabolites, some of which contribute to NAD⁺ biosynthesis, immune function, and brain health.

Explanation of the Kynurenine Pathway

When tryptophan is not used for protein synthesis or serotonin production, it is metabolized through the kynurenine pathway in the liver and immune cells. This pathway plays a critical role in energy metabolism, immune regulation, and neurological function.

Key Functions of the Kynurenine Pathway

  1. NAD⁺ Biosynthesis (Energy Metabolism)
    • Kynurenine is broken down into quinolinic acid, which helps synthesize NAD⁺.
    • This makes tryptophan an indirect but crucial contributor to NAD⁺ levels.
    • Pathway: Tryptophan→Kynurenine→3−Hydroxykynurenine→QuinolinicAcid→NAD+Tryptophan \rightarrow Kynurenine \rightarrow 3-Hydroxykynurenine \rightarrow Quinolinic Acid \rightarrow NAD⁺Tryptophan→Kynurenine→3−Hydroxykynurenine→QuinolinicAcid→NAD+
  2. Immune System Regulation
    • The enzyme IDO (Indoleamine 2,3-Dioxygenase) converts tryptophan into kynurenine, which regulates inflammation and immune responses.
    • This process suppresses excessive immune activation, preventing autoimmune reactions.
  3. Neurological Function (Brain Health)
    • Some kynurenine metabolites influence brain function and mood.
    • Quinolinic acid (a byproduct) is neurotoxic in excess and has been linked to neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s).
    • Kynurenic acid (another byproduct) is neuroprotective and helps regulate glutamate levels in the brain.

Major Enzymes Involved in the Kynurenine Pathway

✅ Tryptophan 2,3-Dioxygenase (TDO) – Converts tryptophan into kynurenine in the liver.
✅ Indoleamine 2,3-Dioxygenase (IDO) – Regulates immune responses and inflammation.
✅ Kynurenine Monooxygenase (KMO) – Converts kynurenine into 3-hydroxykynurenine, which influences NAD⁺ production and brain function.

Kynurenine Pathway and NAD⁺ Production

  • About 90% of dietary tryptophan is processed through the kynurenine pathway.
  • A portion of kynurenine metabolites is eventually used to generate NAD⁺, making this pathway essential for energy metabolism.
  • If NAD⁺ levels are low, the body will increase the kynurenine pathway’s activity to compensate.

Potential Issues with the Kynurenine Pathway

❌ Overactivation of the pathway (due to chronic stress, inflammation, or immune activation) can produce excess quinolinic acid, which is neurotoxic.
❌ Imbalances in kynurenine metabolism have been linked to mood disorders, chronic fatigue, neurodegenerative diseases, and immune dysfunction.
❌ Nutrient deficiencies (Vitamin B6, B2, and B3) can disrupt this pathway, leading to low NAD⁺ levels and poor brain function.

Pro Tip: Optimizing the kynurenine pathway through diet, lifestyle, and stress management can enhance NAD⁺ production, brain health, and immune balance.