Dihydrobiopterin

Dihydrobiopterin
L-erythro-7,8-dihydrobiopterin
Names
IUPAC name
2-Amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-1H-pteridin-4-one
Other names
7,8-Dihydrobiopterin
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
KEGG
PubChem CID
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C9H13N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3,6,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,6-/m0/s1 checkY
    Key: FEMXZDUTFRTWPE-DZSWIPIPSA-N checkY
SMILES
  • CC(C(C1=NC2=C(NC1)NC(=NC2=O)N)O)O
Properties
Chemical formula
 C9H13N5O3
Molar mass 239.235 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Dihydrobiopterin (BH2) is a pteridine compound produced in the synthesis of L-DOPA, dopamine, serotonin, norepinephrine and epinephrine. It is restored to the required cofactor tetrahydrobiopterin by dihydrobiopterin reductase.

Biochemistry

Dihydrobiopterin is an intermediate in the pathway to the cofactor, tetrahydrobiopterin, which is used by three aromatic amino acid hydroxylase enzymes which are important in the metabolism of the amino acid phenylalanine and to make the neurotransmitters serotonin, melatonin, dopamine, noradrenaline, and adrenaline.[1]

In higher organisms, tetrahydrobiopterin is derived from guanosine triphosphate by the action of a sequence of three enzymes GTP cyclohydrolase, 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase.[2] The final enzyme performs a stepwise reduction of L-sepiapterin

2D representation of the chemical structure of Q100606475.
L-sepiapterin
+ NADH
 
 
H+
 
Reversible left-right reaction arrow with minor forward substrate(s) from top left and minor reverse product(s) to bottom left
H+
 
 
2D representation of the chemical structure of dihydrobiopterin .
dihydrobiopterin
+ NAD+
 
2D representation of the chemical structure of dihydrobiopterin .
dihydrobiopterin
+ NADH
 
 
2 H+
 
Reversible left-right reaction arrow with minor forward substrate(s) from top left and minor reverse product(s) to bottom left
2 H+
 
 
2D representation of the chemical structure of tetrahydrobiopterin .
tetrahydrobiopterin
+ NAD+
 

In some bacteria, for example Chlorobium tepidum, the reduction of L-sepiapterin leads to the L-threo isomer of dihydrobiopterin.[3]

2D representation of the chemical structure of Q100606475.
L-sepiapterin
+ NADPH
 
 
H+
 
Reversible left-right reaction arrow with minor forward substrate(s) from top left and minor reverse product(s) to bottom left
H+
 
 
2D representation of the chemical structure of Q27133148.
L-threo-7,8-dihydrobiopterin
+ NAPD+
 

Quinonoid isomer

When tetrahydrobiopterin is used in oxidation reactions as an enzyme cofactor, it can be converted into an alternative isomer of the L-erythro-7,8-dihydrobiopterin form of dihydrobiopterin that is involved in the biosynthesis. This compound, called (6R)-L-erythro-6,7-dihydrobiopterin, is unstable and may spontaneously revert to the more stable isomer. Nevertheless, the enzyme 6,7-dihydropteridine reductase acts directly on it to allow its recycling to tetrahydrobiopterin:[4][5]

2D representation of the chemical structure of Q27093537.
quinonoid isomer
+ 2 NADH
 
 
2 H+
 
Reversible left-right reaction arrow with minor forward substrate(s) from top left and minor reverse product(s) to bottom left
2 H+
 
 
2D representation of the chemical structure of tetrahydrobiopterin.
recycled cofactor
+ 2 NAD+
 

See also

  • Pteridine
  • Dihydropteridine reductase deficiency

References

  1. ^ Kappock, T. Joseph; Caradonna, John P. (1996). "Pterin-Dependent Amino Acid Hydroxylases". Chemical Reviews. 96 (7): 2659–2756. doi:10.1021/CR9402034. PMID 11848840.
  2. ^ Werner, Ernst R.; Blau, Nenad; Thöny, Beat (2011). "Tetrahydrobiopterin: Biochemistry and pathophysiology". Biochemical Journal. 438 (3): 397–414. doi:10.1042/BJ20110293. PMID 21867484.
  3. ^ Cho, Seung-Hyun; Na, Jong-Uk; Youn, Hwan; Hwang, Cheol-Sang; Lee, Chang-Hun; Kang, Sa-Ouk (1999). "Sepiapterin reductase producing l-threo-dihydrobiopterin from Chlorobium tepidum". Biochemical Journal. 340 (2): 497–503. doi:10.1042/bj3400497.
  4. ^ Lind, Kirsten E. (1972). "Dihydropteridine Reductase". European Journal of Biochemistry. 25 (3): 560–562. doi:10.1111/j.1432-1033.1972.tb01728.x.
  5. ^ Kono, Haruka; Hara, Satoshi; Furuta, Tadaomi; Ichinose, Hiroshi (2023). "Binding profile of quinonoid -dihydrobiopterin to quinonoid -dihydropteridine reductase examined by in silico and in vitro analyses". The Journal of Biochemistry. 174 (5): 441–450. doi:10.1093/jb/mvad062. PMID 37540845.
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