Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders

Abstract

Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.

Physical activity as a promising alternative for young people with juvenile idiopathic arthritis: Towards an evidence-based prescription

“…It is accepted that during adolescence, physical activity and exercise strengthen individual brain regions and large-scale neural circuits to improve emotional and behavioral regulation ( 137 ). Moreover, at biological level in response to aerobic exercise, KYN levels in the circulation and central nervous system can be reduced ( 138 ). Furthermore, following chronic exercise, IDO activity is decreased, the content of metabolic product KYN in the TRP/KYN pathway in the brain is reduced, and the concentration of free TRP is increased, so that it can enter the brain more easily through the blood-brain barrier and be metabolized into bioactive compounds such as serotonin and melatonin, which could decrease depression severity ( 138 ).…”

Molecular Docking and Dynamics Simulation revealed the Potential Inhibitory Activity of Piomozide against Kynurenine metabolism targeting the Kynurenine 3-monooxygenase

“…Kynurenine pathway is an established metabolic pathway that involves the conversion of tryptophan into two main metabolites, namely quinolinic acid (QUIN) and kynurenic acid (KYNA).The process is regulated by enzymes such as indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO) (Heyes et al 1992). In the presence of oxygen, TDO catalyzes the rst step of Trp metabolism, forming 5hydroxytryptophan (5-HTP), which is subsequently converted by KMO to QUIN or KYNA (Li et al 2022).…”

Copper(ii) phthalocyanine as an electrocatalytic electrode for cathodic detection of urinary tryptophan

“…1,2 It plays crucial roles in various physiological functions, such as neural activity, immune response, and maintaining gut balance. 3 Given the human body's inability to independently synthesize tryptophan, its levels are intricately regulated through external sources, including diet and medications. Recent studies reveal that abnormal tryptophan levels in biological fluids may serve as potential biomarkers for conditions such as depression, [4][5][6] multiple sclerosis, 7,8 schizophrenia, 9,10 autism spectrum disorder, [11][12][13] epilepsy, 14 bipolar disorder, 1,2 and cancer.…”

“…Recent studies reveal that abnormal tryptophan levels in biological fluids may serve as potential biomarkers for conditions such as depression, [4][5][6] multiple sclerosis, 7,8 schizophrenia, 9,10 autism spectrum disorder, [11][12][13] epilepsy, 14 bipolar disorder, 1,2 and cancer. 3,[15][16][17] Consequently, there has been a notable surge in the demand for tryptophan analysis, highlighting its growing importance in diagnosing and understanding various medical conditions. 18 To evaluate tryptophan levels in biological and pharmaceutical samples and explore the physiological and cognitive functions of tryptophan, various detection methods have been introduced.…”