TY - BOOK
T1 - Acute and chronic effects of endurance exercise on Tryptophan metabolism in middle aged women and persons with MS
AU - Koliamitra, Christina
N1 - Kumulative Dissertation
PY - 2021
Y1 - 2021
N2 - Tryptophan (Trp) is an essential amino acid involved in different biological processes. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a non-polar aromatic amino acid. It is important in humans and since the human body cannot synthesize it, it must be obtained through nutrition in order to maintain the nitrogen balance in the human body (Slominski et al., 2002, Cervenka et al., 2017b). There are two antagonistic pathways in Trp metabolism: the serotonergic pathway, that results in the production of monoaminergic neurotransmitters (e.g. serotonin and melatonin) regulating human behavior, appetite and tiredness (Badawy, 2017; Cervenka et al., 2017; Leklem, 1971) and the kynurenine (Kyn) pathway which, when at a central level comports neuro-protective (e.g. Kyn, kynurenic acid) and neuro-toxic metabolites (e.g. quinolinic acid, 3-hydroxykynurenin). Only one percent of the essential amino acid Tryptophan is used for protein synthesis under physiological conditions. While it is just a small portion metabolized through the serotonergic pathway, the highest portion of available Trp is metabolized through the Kyn pathway by the liver-specific enzyme tryptophan 2,3-dioxygenase (TDO) (Badawy, 2017; Cervenka et al., 2017; Chen & Guillemin, 2009; Leklem, 1971). However, Trp metabolism can additionally take place in the lungs, kidneys, spleen, placenta and blood cells by the enzyme indole 2,3-dioxygenase (IDO) (Braidy et al., 2011; Chen & Guillemin, 2009; Strasser et al., 2017).
Higher breakdown of Trp to Kyn during inflammatory conditions redirects an increase in the activity of IDO, which can be indirectly determined by an elevated Kyn/Trp ratio (Schröcksnadel et al., 2006). Contrary to the effect of IDO induction, there have been cases with no increase in plasma Kyn under inflammatory circumstances, possibly explained through the upregulation of kynurenine 3- monooxygenase (KMO) (Badawy & Guillemin, 2019). Reduction of plasma tryptophan or increased Kyn - Trp ratio are described during viral, bacterial and parasitic intracellular infections (Boasso et al., 2007; Moreau et al., 2005; Murray, 2003; Silva et al., 2002) or experimentally induced inflammation (Melchior et al., 2004). Increased tryptophan utilization is also reported during other situations of long- lasting immune activation such as cancer (Denz et al., 1993; Liu et al., 2010), acquired immunodeficiency syndrome (AIDS) (Huengsberg et al., 1998), major trauma (Pellegrin et al.,
9
2005) and autoimmune, inflammatory diseases (e.g. MS) (Wolf et al., 2004). Metabolic disorders of the Kyn pathway are linked to the pathogenesis and progression of various chronic diseases. Dysregulations were discovered in diseases involving the central nervous system (CNS) (e. g. Multiple Sclerosis, Alzheimer’s disease or Parkinson’s disease (Campbell et al., 2014; Vécsei et al., 2013) and several internal pathologies (e.g. diabetes mellitus (Cervenka et al., 2017) and cancer (Platten et al., 2019).
Acute and chronic exercise have been shown to have strong influence on Trp metabolism (Metcalfe et al., 2018). Systematic physical activity and exercise interventions are assumed to have anti-inflammatory effects depending on the exercise modality, thus potentially reducing the risk and progress of several chronic diseases. Modifications in the kynurenine pathway may signify a link between inflammatory responses following acute exercise and chronic anti-inflammatory properties, such as increased levels of Tregs (Koliamitra et al., 2019). Tregs consist of a subpopulation of T cells that modulates the immune system, sustains tolerance to self-antigens, and prevents autoimmune diseases. The mechanisms under which this tolerance is mediated are not well understood, but there are findings that have connected tryptophan catabolism through the kynurenine metabolic pathway as one of many mechanisms involved. The enzymes that break down tryptophan through this pathway are found in numerous cell types, including cells of the immune system (Moffett & Namboodiri, 2003). Some of these enzymes are induced by immune activation like IDO. Various studies support the idea that, in addition to defense against pathogens, IDO participates in the regulation of T cell responses (Munn et al., 1999). It has been speculated that expression of IDO in antigen presenting cells of the immune system may control Tregs (Terness et al., 2002). Tregs are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells (Bettelli et al., 2006). Adding all these facts it is clearly implied that tryptophan breakdown is essential for sustaining aspects of immune tolerance.
In this content, two original investigations were conducted on the effect of chronic and acute exercise on Kyn Pathway in persons with MS and healthy women. Supplementary aim of this thesis was to investigate any possible connection with regulatory T cells and the Kyn pathway influence. Additionally, a review screening the scientific background on exercise effects on Kyn Pathway on human subjects was conducted.
AB - Tryptophan (Trp) is an essential amino acid involved in different biological processes. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a non-polar aromatic amino acid. It is important in humans and since the human body cannot synthesize it, it must be obtained through nutrition in order to maintain the nitrogen balance in the human body (Slominski et al., 2002, Cervenka et al., 2017b). There are two antagonistic pathways in Trp metabolism: the serotonergic pathway, that results in the production of monoaminergic neurotransmitters (e.g. serotonin and melatonin) regulating human behavior, appetite and tiredness (Badawy, 2017; Cervenka et al., 2017; Leklem, 1971) and the kynurenine (Kyn) pathway which, when at a central level comports neuro-protective (e.g. Kyn, kynurenic acid) and neuro-toxic metabolites (e.g. quinolinic acid, 3-hydroxykynurenin). Only one percent of the essential amino acid Tryptophan is used for protein synthesis under physiological conditions. While it is just a small portion metabolized through the serotonergic pathway, the highest portion of available Trp is metabolized through the Kyn pathway by the liver-specific enzyme tryptophan 2,3-dioxygenase (TDO) (Badawy, 2017; Cervenka et al., 2017; Chen & Guillemin, 2009; Leklem, 1971). However, Trp metabolism can additionally take place in the lungs, kidneys, spleen, placenta and blood cells by the enzyme indole 2,3-dioxygenase (IDO) (Braidy et al., 2011; Chen & Guillemin, 2009; Strasser et al., 2017).
Higher breakdown of Trp to Kyn during inflammatory conditions redirects an increase in the activity of IDO, which can be indirectly determined by an elevated Kyn/Trp ratio (Schröcksnadel et al., 2006). Contrary to the effect of IDO induction, there have been cases with no increase in plasma Kyn under inflammatory circumstances, possibly explained through the upregulation of kynurenine 3- monooxygenase (KMO) (Badawy & Guillemin, 2019). Reduction of plasma tryptophan or increased Kyn - Trp ratio are described during viral, bacterial and parasitic intracellular infections (Boasso et al., 2007; Moreau et al., 2005; Murray, 2003; Silva et al., 2002) or experimentally induced inflammation (Melchior et al., 2004). Increased tryptophan utilization is also reported during other situations of long- lasting immune activation such as cancer (Denz et al., 1993; Liu et al., 2010), acquired immunodeficiency syndrome (AIDS) (Huengsberg et al., 1998), major trauma (Pellegrin et al.,
9
2005) and autoimmune, inflammatory diseases (e.g. MS) (Wolf et al., 2004). Metabolic disorders of the Kyn pathway are linked to the pathogenesis and progression of various chronic diseases. Dysregulations were discovered in diseases involving the central nervous system (CNS) (e. g. Multiple Sclerosis, Alzheimer’s disease or Parkinson’s disease (Campbell et al., 2014; Vécsei et al., 2013) and several internal pathologies (e.g. diabetes mellitus (Cervenka et al., 2017) and cancer (Platten et al., 2019).
Acute and chronic exercise have been shown to have strong influence on Trp metabolism (Metcalfe et al., 2018). Systematic physical activity and exercise interventions are assumed to have anti-inflammatory effects depending on the exercise modality, thus potentially reducing the risk and progress of several chronic diseases. Modifications in the kynurenine pathway may signify a link between inflammatory responses following acute exercise and chronic anti-inflammatory properties, such as increased levels of Tregs (Koliamitra et al., 2019). Tregs consist of a subpopulation of T cells that modulates the immune system, sustains tolerance to self-antigens, and prevents autoimmune diseases. The mechanisms under which this tolerance is mediated are not well understood, but there are findings that have connected tryptophan catabolism through the kynurenine metabolic pathway as one of many mechanisms involved. The enzymes that break down tryptophan through this pathway are found in numerous cell types, including cells of the immune system (Moffett & Namboodiri, 2003). Some of these enzymes are induced by immune activation like IDO. Various studies support the idea that, in addition to defense against pathogens, IDO participates in the regulation of T cell responses (Munn et al., 1999). It has been speculated that expression of IDO in antigen presenting cells of the immune system may control Tregs (Terness et al., 2002). Tregs are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells (Bettelli et al., 2006). Adding all these facts it is clearly implied that tryptophan breakdown is essential for sustaining aspects of immune tolerance.
In this content, two original investigations were conducted on the effect of chronic and acute exercise on Kyn Pathway in persons with MS and healthy women. Supplementary aim of this thesis was to investigate any possible connection with regulatory T cells and the Kyn pathway influence. Additionally, a review screening the scientific background on exercise effects on Kyn Pathway on human subjects was conducted.
M3 - Dissertations
BT - Acute and chronic effects of endurance exercise on Tryptophan metabolism in middle aged women and persons with MS
PB - Deutsche Sporthochschule Köln
CY - Köln
ER -
