Affiliation:
1. Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade,Serbia
2. Clinic for Internal Medicine, Department of Endocrinology and Diabetes, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade,Serbia
Abstract
:
The essential amino acid tryptophan (Trp) undergoes catabolism through several
pathways, producing biologically active metabolites that significantly impact physiological
processes. The metabolic pathway responsible for the majority of Trp catabolism
is the kynurenine synthesis pathway (KP). Serotonin and melatonin are among the most
essential Trp pathways degradation products. It has emerged that a strong relationship exists
between alterations in Trp metabolism and the onset and progression of atherosclerosis
and diabetes.
Atherosclerosis is a chronic inflammatory disease of the small and medium arteries wall
caused by maladaptive local immune responses, which underpins several cardiovascular
diseases (CVD). Systemic low-grade immune-mediated inflammation is implicated in
atherosclerosis where pro-inflammatory cytokines, such as interferon-γ (IFN-γ), play a
significant role. IFN-γ upregulates the enzyme indoleamine 2,3-dioxygenase (IDO), decreasing
serum levels of the Trp and increasing metabolite levels of kynurenine. Increased
IDO expression and activity could accelerate the atherosclerosis process. Therefore, activated
IDO inhibition could offer possible treatment options regarding atherosclerosis
management. Diabetes is a chronic metabolic disease characterized by hyperglycemia
that, over time, leads to severe damage to the heart, blood vessels, eyes, kidneys, and peripheral
nerves. Trp serum levels and lower activity of IDO were higher in future type 2
diabetes (T2DM) patients. This article reviews recent findings on the link between mammalian
Trp metabolism and its role in atherosclerosis and diabetes and outlines the intervention
strategies.
Funder
Ministry of Education, Science, and Technological Development of the Republic of Serbia
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
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