Abstract
Scientific interest in tryptophan metabolism via the kynurenine pathway (KP) has increased in the last decades. Describing its metabolites helped to increase their roles in many diseases and disturbances, many of a pro-inflammatory nature. It has become increasingly evident that KP can be considered an important part of emerging mediators of diabetes mellitus and metabolic syndrome (MS), mostly stemming from chronic systemic low-grade inflammation resulting in the aggravation of cardiovascular complications. An electronic literature search of PubMed and Embase up to March 2021 was performed for papers reporting the effects of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), anthranilic acid (AA), and quinolinic acid (QA), focusing on their roles in carbohydrate metabolism and the cardiovascular system. In this review, we discussed the progress in tryptophan metabolism via KP research, focusing particular attention on the roles in carbohydrate metabolism and its complications in the cardiovascular system. We examined the association between KP and diabetes mellitus type 2 (T2D), diabetes mellitus type 1 (T1D), and cardiovascular diseases (CVD). We concluded that tryptophan metabolism via KP serves as a potential diagnostic tool in assessing cardiometabolic risk for patients with T2D.
Highlights
Tryptophan (TRP) is an essential exogenous amino acid that intermediates in human protein synthesis and has critical metabolic functions as a substrate for crucial molecules such as serotonin—(the neurotransmitter), nicotinamide adenine dinucleotide (NAD), and nicotinic acid [1]
A recently published review summarizes the role of kynurenine pathway (KP) in metabolic disorders including aging, atherosclerosis, obesity and diabetes [6]
The present literature review aims to provide an overview of the current findings of the involvement of kynurenine pathway metabolites in the pathogenesis of carbohydrate metabolism disorders and its associations with cardiovascular complications of diabetes
Summary
Tryptophan (TRP) is an essential exogenous amino acid that intermediates in human protein synthesis and has critical metabolic functions as a substrate for crucial molecules such as serotonin—(the neurotransmitter), nicotinamide adenine dinucleotide (NAD), and nicotinic acid [1]. A recently published review summarizes the role of KP in metabolic disorders including aging, atherosclerosis, obesity and diabetes [6]. The present literature review aims to provide an overview of the current findings of the involvement of kynurenine pathway metabolites in the pathogenesis of carbohydrate metabolism disorders and its associations with cardiovascular complications of diabetes. The process begins when TRP, an exogenous amino acid, is converted to unstable N-formylo-L-kynurenine. This step is catalyzed by two independent enzymes belonging to the oxidoreductase family: tryptophan 2,3-dioxygenase (TDO). This review summarizes clinical and experimental studies on the role of KP metabolites in diabetes and cardiometabolic risk factors (such as cardiovascular diseases, heart failure, and atherosclerosis). The search included the terms “kynurenine pathway”, “tryptophan metabolism”, “indoleamine 2,3-dioxygenase”, “kynurenic acid”, “xanthurenic acid”, “3-hydroxykynurenine”, “3-
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