Figure 4.

Candidate genes in the dopamine and serotonin system. Sepiaperterin reductase (SPR) and aldo-keto reductase (AKR) reduces an intermediate, 6-pyruvoyl-tetrahydropterin (PPH4), to 1'-OXPH4, or 2'-OXPH4, and catalyzes the final step of tetrahydrobiopterin (BH4) synthesis, an essential cofactor for phenylalanine hydroxylase, tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH) and nitric oxide synthase (NOS) [65,66]. Quinoid dihydropteridine reductase (QDPR) mediates reduction of quinonoid dihydrobiopterin. Several candidate genes are related to dopamine function. Snca regulates dopamine biosynthesis and attenuates dopamine transporter activity. Scap2 phosphorylates Snca, and Copg2 is involved in the transport of the dopamine receptor 1 (D1). Arrows represent metabolic steps, and dashed lines represent genes that are functionally related. Identified candidate genes are in boxes; gray color indicates a lower expression in iP and white color indicates higher expression in iP. GTPCH, GTP-cyclohydrolase I; PTPS, 6-pyruvoyltetrahydropterin synthase; 1'-OXPH4, 1'-oxo-2'-hydroxypropyl tetrahydropterin; 2'-OXPH4, 1'-hydroxy-2'-oxo-tetrahydropterin; OH-4a-BH4, pterin-4a-carbinolamine; PCD, pterin-4a-carbinolamine dehydratase.