Tryptophan metabolism and inflammatory pathways
The tryptophan It is an essential amino acid with very limited reserves, easily subject to deficiency and metabolic deviation. Only a small part generates serotonin, while approximately 95% is directed towards the path of kynurenine, activated by enzymes IDO And TDO. When the immune system produces inflammatory cytokines, IDO increases its activity and accelerates the transformation of tryptophan, reducing its availability for serotonin synthesis and generating potentially harmful metabolites. Among these, a particularly critical role is played byacid quinoline, capable of activating the NMDA receptors and generate oxidative stress.
Quinolinic acid and neurodegeneration
The increase of thequinolinic acid It is detected in different conditions: depression, Parkinson, Alzheimer, ALS and cognitive disorders associated with HIV. In depressed patients, levels in the cerebrospinal fluid are higher and correlate with the severity of symptoms. In Parkinson’s disease, it contributes to the death of dopaminergic neurons; in Alzheimer’s disease, it is associated with inflammation, plaques And neurofibrillary tangles; in ALS it causes motor neuron damage and mitochondrial dysfunction. In HIV-positive patients, levels can increase up to twenty-fold, causing severe cognitive impairment. Its neurotoxicity results from excessive activation of NMDA receptors, the production of free radicals and from the alteration of the neuronal cytoskeleton.
Therapeutic perspectives
The evidence shows that the tryptophan dysregulation and excessive production of quinolinic acid contribute to inflammation, oxidative stress and loss of protective metabolites such as acid picolinic and acid kynurenic. For this reason, research aims to modulate the kynurenine pathway, reducing the flow towards toxic metabolites and promoting neuroprotective ones. IDO/TDO inhibitors and antioxidants such as glutathione, curcumin or epigallocatechin, and nutritional approaches that ensure adequate tryptophan levels and support antioxidant defenses. These strategies may help prevent brain degeneration, but long-term clinical studies are needed.
For further information:
Friedman M. Analysis, Nutrition, and Health Benefits of Tryptophan. Int J Tryptophan Res. 2018 Sep 26;11:1178646918802282. doi: 10.1177/1178646918802282.
Hestad K, et al. The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases. Biomolecules. 2022 Jul 18;12(7):998. doi: 10.3390/biom12070998.
OMahony SM, et al. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015 Jan 15;277:32-48. doi: 10.1016/j.bbr.2014.07.027.