Emina Sudar-Milovanovic*, Zoran Gluvic, Milan Obradovic, Bozidarka Zaric and Esma R. Isenovic* Pages 99 - 113 ( 15 )
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.
Tryptophan, kynurenine pathway, indoleamine 2,3-dioxygenase, kynurenine, atherosclerosis, diabetes
Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Clinic for Internal Medicine, Department of Endocrinology and Diabetes, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade, Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade