Tryptophan availability for kynurenine pathway metabolism across the life span: Control mechanisms and focus on aging, exercise, diet and nutritional supplements

Abstract

Tryptophan (Trp) availability for the kynurenine pathway (KP) across the life span is discussed. Free (non-albumin-bound) plasma Trp is the major determinant of the flux of Trp down the KP. Flux is the major determinant of kynurenine metabolite formation and is more effective than induction of hepatic Trp 2,3-dioxygenase (TDO) or extrahepatic indoleamine 2,3-dioxygenase (IDO). Flux is better expressed using the sum of plasma kynurenine and its metabolites, rather than kynurenine only. Under normal conditions, TDO controls Trp flux in liver and availability in plasma and can supply kynurenine for the extrahepatic pathway. Under certain pathological conditions associated with immune activation, IDO assumes the major role in control of Trp availability. Plasma Trp availability is increased during pregnancy, at birth, and by exercise, high protein and fat intake. Aging does not seem to exert a major effect on plasma Trp. Assessment of plasma Trp availability in health and disease requires measurement of concentrations of both free and total [Trp] in the first instance, followed, if necessary, by those of albumin and the physiological displacers of albumin-bound Trp, non-esterified fatty acids. Additional measures should include cortisol, cytokines, kynurenine and its metabolites. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

Keywords: Albumin; Glucose; Indoleamine 2,3-dioxygenase; Non-esterified fatty acids; Tryptophan 2,3-dioxygenase.