Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes - Fig 2

Divergent effects of moderate vs. exhaustive physical exercise on the production of neurotransmitters: Pro-inflammatory cytokines like interferon-y (IFN-y) stimulates several enzymes including [a] indoleamine 2,3-dioxygenase-1 (IDO1), which degrades tryptophan (TRP) and serotonin (5HT), [b] NADPH oxidase (NOx), which produces reactive oxygen species (ROS), and [c] GTP-cyclohydrolase-1 (GCH1), which in human macrophages forms neopterin and in other cells tetrahydrobiopterin (BH₄), the necessary cofactor of several amino acid hydroxylases, including tryptophan 5-hydroxylase (TH) for the production of 5-hydroxytryptamine (5HT, serotonin) and phenylalanine 4-hydroxylase (PAH) for the production of tyrosine, precursor of dopamine, adrenaline and noradrenaline. Physical exercise is followed by a pro-inflammatory immune response which induces BH₄, thereby upregulating several neurotransmitters (see pathways marked in red), associated with mood enhancement and well-being. However, when physical exercise or training is too heavy and exhaustive, tryptophan breakdown by IDO1 becomes too drastic and the decline of tryptophan due to IDO1 activity can no longer be compensated by BH₄, the life span of the latter is decreased by ROS exposure. Thus, athletes may suffer from insufficient supply with neurotransmitters and will experience low mood.