KT Ratio (Plasma)

KT Ratio stands for Kynurenine/Tryptophan Ratio (KTR).

What is Tryptophan?

Tryptophan is involved in serotonin production and is the least abundant amino acid. Tryptophan is an essential amino acid necessary for the synthesis of serotonin (serotonin regulates many physiological functions such as sleep, appetite, mood, thermoregulation, etc), melatonin, vitamin b3, as well as kynurenine. 

What is Kynurenine?

Kynurenine is a compound produced during the conversion of tryptophan to niacin that is associated with depression when accumulated in the brain.

The kynurenine-tryptophan ratio (KTR) is a key marker of tryptophan catabolism along the kynurenine pathway, through the enzymatic activity of indoleamine 2,3-dioxygenase (IDO1/2) or tryptophan 2,3-dioxygenase (TDO2).

KTR has been described to be increased in a wide range of pathological contexts, including: 

- cancers,

- infectious diseases,

- depression, schizoprenia, 

- Hydroxykynureninuria

- ALS

- Parkinson's disease

- as well as neurological disorders.

What is the kynurenine pathway?

The kynurenine pathway is a metabolic pathway leading to the production of nicotinamide adenine dinucleotide (NAD+) from the enzymatic conversion of tryptophan. Immune activation leads to the formation of kynurenine with corresponding loss of tryptophan.

>> Stress signaling hormones induce pathway activation. The IDO enzyme is activated by IL-1 (Interleukin-1), IL-6 (Interleukin-6) and TNF (tumor necrosis factor) and the TDO enzyme is activated by Cortisol (= stress hormone). This activation leads to the metabolism of Tryptophan down the kynurenine pathway and the serotonin/melatonin production is reduced.

>> End products of this pathway are Quinolinic Acid and Picolinic Acid

>> Quinolinic acid has neurotoxic effects and is NMDA receptor agonist.

>> Quinolinic acid may also be involved in psychiatric disorders.

- The Kynurenine/Tryptophan Ratio estimates activity of the extrahepatic tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO).

- Plasma or urine levels have been correlated with interferon-γ activity and considered a marker of systemic inflammation. The Kynurenine/Tryptophan Ratio has also been noted as a marker for neuroinflammation.

>> Interferon (IFN)-g and other cytokines activate IDO, while NO and excess tryptophan inhibit its activity.

- Higher Kynurenine/Tryptophan blood levels have been associated with a higher BMI, obesity, inflammation, renal failure & CKD, cancer, AIDS, sepsis, pregnancy, ALS, reduced cognition, CVD. The GSH/GSSG ratio correlated negatively with blood Kynurenine/Tryptophan; Kynurenine/Tryptophan rises as glutathione is used. Systemic tryptophan and kynurenine levels change upon aging and in age-related diseases.

- Upregulation of other tryptophan breakdown enzymes kynurenine monooxygenase (KMO) and kynureninase (KYNU) may decrease kynurenine, resulting in a decrease in Kynurenine/Tryptophan.

- Weight loss resulted in a decreased Kynurenine/Tryptophan Ratio, along with a reduction of tryptophan, kynurenine, and CRP, and an increase in vitamin B6.