TH and pulmonary arterial hypertension: The increase of PAH activity, indicated by PHE/TYR, could result from the increased activity of GCH1, which is reflected by the increase of monocyte-macrophage-derived neopterin that is usually accompanied by a similar increase of 5,6,7,8-tetrahydrobiopterin (BH4), the cofactor of PAH and also tyrosine hydroxylase, as well as tryptophan hydroxylase, enzymes that are all important in the formation of relevant neurotransmitters [30] (Fig 2).