Category: biosynthesis
BH4 (tetrahydrobiopterin) is the obligate cofactor for the aromatic amino acid hydroxylases — TYROSINE HYDROXYLASE (TH, catecholamine synthesis), TRYPTOPHAN HYDROXYLASE (TPH, serotonin synthesis), PHENYLALANINE HYDROXYLASE (PAH, PKU enzyme) — and for all three NITRIC OXIDE SYNTHASE isoforms (NOS1/2/3). De novo synthesis: GTP → 7,8-dihydroneopterin triphosphate (GTPCH1, rate-limiting + tightly regulated) → multi-step → BH4. Salvage: 7,8-dihydrobiopterin → BH4 via DHFR. After each hydroxylation reaction BH4 is oxidized to BH2; recycled by DHPR (dihydropteridine reductase). DHPR deficiency causes a PKU-like phenotype because functional PAH activity fails despite intact enzyme protein. SAPROPTERIN = synthetic BH4 used to rescue mild PAH deficiency. BH4 deficiency also causes monoamine deficiency syndromes — treated with L-DOPA + 5-HTP supplementation.