Figure 2.

Hypothesis of the impact of moderate (upper graph) versus intensive (lower graph) physical exercise on the breakdown of tryptophan and the production of 5-hydroxytryptamine (serotonin) in a healthy individual: Physical exercise evokes a proinflammatory immune response, which is associated with induction of IDO1. In parallel, GCH1 is activated, which leads to the production of BH₄, the necessary cofactor of several amino acid hydroxylases, including tryptophan 5-hydroxylase. In the moderate situation (upper graph), the increase in BH₄ is able to compensate for a possible loss of tryptophan due to IDO1 activity, increased serotonin availability will enhance mood. However, in the situation after prolonged or heavy (= intensive) exercise (lower graph), this is no longer true. High level production of ROS can reduce the life span of BH₄, and athletes may be faced to insufficient supply with serotonin and low mood.