Tetrahydrobiopterin
1053052
223411438
2008-07-03T23:29:41Z
DOI bot
6652755
Citation maintenance. Formatted: title. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]].
{{drugbox |
| IUPAC_name = (6''R'')-2-Amino-6-[(1''R'',2''S'')-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(1''H'')-pteridinone
| image = Tetrahydrobiopterin structure.png
| CAS_number = 17528-72-2
| ATC_prefix =
| ATC_suffix =
| ATC_supplemental =
| PubChem = 44257
| DrugBank =
| C=9|H=15|N=5|O=3
| molecular_weight = 241.25
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| pregnancy_AU =
| pregnancy_US = C
| legal_AU =
| legal_UK =
| legal_US = Rx-only
| routes_of_administration = Oral
| licence_US =Kuvan
}}
'''Tetrahydrobiopterin''', '''sapropterin''', or '''BH<sub>4</sub>''' is a naturally occurring essential [[Cofactor (biochemistry)|cofactor]] of the three aromatic amino acid hydroxylases;[[phenylalanine hydroxylase | phenylalanine-4-hydroxylase]] for conversion of [[phenylalanine]] to [[tyrosine]], [[tyrosine-3-hydroxylase]] for the conversion of tyrosine to [[L-dopa]], and [[tryptophan-5-hydroxylase]] for the conversion of [[tryptophan]] to [[5-hydroxytryptophan]]. It is also essential for the synthesis of [[nitric oxide]] by [[nitric oxide synthase]] (NOS).
==Clinical significance==
A defect in BH<sub>4</sub> synthesis and/or regeneration causes [[phenylketonuria]] type IV, as well as neurotransmitter (dopamine and serotonin) deficiency. Prolonged elevations in blood Phe levels in patients with PKU can result in severe
neurologic damage, including severe mental retardation, microcephaly, delayed speech, seizures,
and behavioral abnormalities.
Sapropterin, under the tradename Kuvan, is a synthetic preparation of the dihydrochloride salt of tetrahydrobiopterin.<ref>{{cite journal| journal=Nature Reviews Drug Discovery |volume=7 |pages=199–200 |year=2008) |doi=10.1038/nrd2540 |title=Fresh from the Pipeline: Sapropterin |author=Barbara K. Burton, Santwana Kar & Peter Kirkpatrick}}</ref> It was developed by BioMarin and approved by the [[United States|US]] [[Food and Drug Administration]] on [[December 13]],[[2007]]. It is sold as tablets containing 100 mg. Sapropterin is the only drug approved for the treatment of [[phenylketonuria]] (PKU). Kuvan is indicated to reduce blood phenylalanine (Phe) levels in
patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU).
Kuvan is to be used in conjunction with a Phe-restricted diet.
==Synthesis==
Tetrahydrobiopterin is synthesized from [[GTP]] by three enzymatic reactions (GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reductase).<ref>{{cite journal | author=Thony B, Auerbach G, Blau N | title=Tetrahydrobiopterin biosynthesis, regeneration and functions | journal=Biochem J | year=2000 | pages=1–16 | volume=347 Pt 1 |pmid=10727395 |url=http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=10727395 | doi=10.1042/0264-6021:3470001}}</ref>
==History==
Tetrahydrobiopterin has been discovered to play a role as biological cofactor by Seymour Kaufman. The first enzyme found to use tetrahydrobiopterin was [[phenylalanine hydroxylase]]. <ref> {{cite journal |author=Kaufman, S |title=A New Cofactor Required for the Enzymatic Conversion of Phenylalanine to Tyrosine |journal=J. Biol. Chem. |issue= 230 |pages= 931–39 |year= 1958 |url=http://www.jbc.org/cgi/reprint/230/2/931}}</ref>
==See also==
* [[Tetrahydrobiopterin deficiency]] leading to [[phenylketonuria]]
==References==
{{reflist}}
==External links==
* [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=261640 Coenzyme tetrahydrobiopterin (BH4)]
* [http://www.bh4.org/ Tetrahydrobiopterin website]
* [http://www.kuvan.com/ Kuvan website], run by BioMarin
* [http://www.fda.gov/cder/foi/label/2007/022181lbl.pdf Prescribing information]
* [http://www.PKU.com/ Information on PKU]
[[Category:Coenzymes]]
{{Enzyme cofactors}}
[[fr:Tétrahydrobioptérine]]
[[ru:Тетрагидробиоптерин]]