Regulation of DA synthesis in dependency on BH4. Dopamin synthesis relies on hydroxylation of phenylalanine, hydroxylation of tyrosine and decarboxylation of DOPA (blue box). The key enzyme tyrosine hydroxylase (TH) needs tetrahydrobiopterine (BH4) as a cofactor to catalyze the hydroxylation of tyrosine. Guanosine triphosphate (GTP) is the precursor for BH4 synthesis and GTP cyclohydrolase I is the key enzyme in this reaction (grey box). GTP cyclohydrolase I converts GTP into 7,8-dihydroneopterine triphosphate which is subsequently converted into 6-pyruvoyltetrahydropterine by PTPS. SR finally converts 6-pyruvoyltetrahydropterine into BH4. GTPCH is stimulated by Phenylalanine and repressed by high BH4 levels. in this case BH4 binds to the GTPCH feedback regulatory protein (GFRP). BH4 can be recycled via pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) to maintain sufficient BH4 (yellow box).