Table 1 Human BH4 metabolic and BH4 cofactor-dependent enzymes

AKR1B1, aldose reductase 1B1; AKR1C3, 3α-hydroxysteroid dehydrogenase type 3; CBR1, carbonyl reductase 1; eNOS, endothelial NOS; iNOS, inducible NOS; nNOS, neuronal NOS; OMIM, Online Mendelian Inheritance in Man.

EnzymeEC numberGene symbolOMIM numberChromosome locationNumber of exons (amino acids)Size (kDa×number of subunits)Mouse model
GTPCH3.5.4.16GCH160022514q22.1-q22.26 (250)27.9×10Not available
hph-1 [177181]
GFRP (P35)NoneGCHFR60243715q153 (84)9.7×5Gchfr conditional ko
PTPS4.2.3.12*PTS61271911q22.3-q23.36 (145)16.4×6Pts-ko [182,183]/Pts-ki [184]
SR1.1.1.153SPR1821252p133 (261)28.0×2Spr-ko [185]
CR (CBR1)1.1.1.184CBR111483021q22.133 (277)30.4×2Not available
AR (AKR1B1)1.1.1.21AKR1B11038807q3510 (316)35.9×2Akr1b1-ko [193]
AKR1C31.1.1.213AKR1C360396610p15-p149 (323)36.9×2Not available
DHFR1.5.1.3DHFR1260605q11.2-q13.26 (187)21.5×2Not available
PCD/DCoH14.2.1.96PCBD112609010q224 (103)11.9×4§DCoH-ko [187]
DHPR1.6.99.7QDPR6126764p15.37 (244)25.8×2Qdpr-ko [189]
PAH1.14.16.1PAH61234912q24.14 (452)51.9×2 or×4enu1/enu2 [194,195]
TH (TYH)1.14.16.2TH19129011p15.514 (TH-4; 528)58.5×4Th-ko [196,197]
TPH1 (TPRH, TRPH)1.14.16.4TPH119106011p15.3-p1411 (444)51.0×4Tph1-ko [198]
TPH2 (NTPH)1.14.16.4TPH260747812q1511 (490)65.0×4Tph2-(conditional) ko [199201]
AGMO (TMEM195)1.14.16.5AGMO6137387p21.213 (445)51.5×?Agmo conditional ko
NOS1 (nNOS, NOSI)1.14.19.39NOS116373112q24.2-q24.3128 (1434)161.0×2nNos-ko [205]
NOS2 (iNOS, mNOS, NOSII)1.14.19.39NOS216373017cen-q11.227 (1153)131.1×2iNos-ko [205]
NOS3 (eNOS, ECNOS, NOSIII)1.14.19.39NOS31637297q3626 (1203)133.3×2eNos-ko [205]
  • *EC 4.6.1.10 created in 1999; deleted in 2000.

  • †D. Adamsen, T. Scherer, N. Blau and B. Thöny, unpublished work.

  • ‡In liver, the protein was found to lack the starting methionine residue.

  • §Homotetrameric (α4) only as a carbinolamine dehydratase, heterotetrameric (α2β2) in complex with HNF-1α.

  • ∥For TH, four splice variants in intron 1 exist, TH-1 (13 exons, 497 amino acids), TH-2 (13 exons, 501 amino acids), TH-3 (14 exons, 524 amino acids) and TH-4 (14 exons, 528 amino acids) [227].

  • ¶K. Watschinger, N. Yannoutsos, M.A. Keller, G. Golderer, G. Werner-Felmayer and E.R. Werner, unpublished work.