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Tetrahydrobiopterin
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| Systematic (IUPAC) name | |
| (6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone | |
| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | |
| ChemSpider | |
| Chemical data | |
| Formula | C9H15N5O3 |
| Mol. mass | 241.25 |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Licence data |
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| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | Oral |
Tetrahydrobiopterin, sapropterin, or BH4 is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylases; 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).
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Clinical significance
A defect in BH4 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.1 It was developed by BioMarin and approved by the 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-pyruvoyltetrahydropterin synthase, and sepiapterin reductase).2
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. 3
See also
- Tetrahydrobiopterin deficiency leading to phenylketonuria
References
- ^ Barbara K. Burton, Santwana Kar & Peter Kirkpatrick (2008)). "Fresh from the Pipeline: Sapropterin". Nature Reviews Drug Discovery 7: 199–200. doi:.
- ^ Thony B, Auerbach G, Blau N (2000). "Tetrahydrobiopterin biosynthesis, regeneration and functions". Biochem J 347 Pt 1: 1–16. doi:. PMID 10727395, http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=10727395.
- ^ Kaufman, S (1958). "A New Cofactor Required for the Enzymatic Conversion of Phenylalanine to Tyrosine". J. Biol. Chem. (230): 931–39, http://www.jbc.org/cgi/reprint/230/2/931.
External links
- Coenzyme tetrahydrobiopterin (BH4)
- Tetrahydrobiopterin website
- Kuvan website, run by BioMarin
- Prescribing information
- Information on PKU
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Wikipedia content modification information:
- This page was last modified on 9 October 2008, at 00:46.
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