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药品详细

Tetrahydrobiopterin(四氢生物蝶呤)

化学结构式图
中文名
四氢生物蝶呤
英文名
Tetrahydrobiopterin
分子式
C9H15N5O3
化学名
2-amino-6-(1,2-dihydroxypropyl)-1,4,5,6,7,8-hexahydropteridin-4-one
分子量
Average: 241.2471
Monoisotopic: 241.117489371
CAS号
17528-72-2
ATC分类
A16A Other Alimentary Tract and Metabolism Products
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase. [Wikipedia]

生产厂家
  • Biomarin pharmaceutical inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Thony B, Auerbach G, Blau N: Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J. 2000 Apr 1;347 Pt 1:1-16. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Pterins
Substructures
  • Pterins
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Pyrimidines and Derivatives
  • Amino Alcohols
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
适应症
药理
Indication For the treatment of tetrahydrobiopterin (BH4) deficiency.
Pharmacodynamics Tetrahydrobiopterin (BH4) is used to convert several amino acids, including phenylalanine, to other essential molecules in the body including neurotransmitters. Tetrahydrobiopterin deficiency can be caused by mutations in GTP cyclohydrolase 1 (GCH1), 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (PCBD1), 6-pyruvoyltetrahydropterin synthase (PTS), and quinoid dihydropteridine reductase (QDPR) genes. These genes make the enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. High levels of phenylalanine can result in signs and symptoms ranging from temporary low muscle tone to mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.
Mechanism of action Tetrahydrobiopterin (BH4) is a natural co-factor or co-enzyme for phenylalanine-4-hydroxylase (PAH),Tetrahydrobiopterine, and tryptophan-5-hydroxylase. Tetrahydrobiopterin is also a natural co-factor for nitrate oxide synthase. Therefore BH4 is required for the conversion of phenylalanine to tyrosine, for the production of epinephrine (adrenaline) and the synthesis of the monoamine neuro-transmitters, serotonin, dopamine, and norepinephrine (noradrenaline). It is also involved in apoptosis and other cellular events mediated by nitric oxide production. As a coenzyme, BH4 reacts with molecular oxygen to form an active oxygen intermediate that can hydroxylate substrates. In the hydroxylation process, the co-enzyme loses two electrons and is regenerated in vivo in an NADH-dependent reaction. As a co-factor for PAH, tetrahydrobiopterin allows the conversion of phenylalanine to tyrosine and reduces the level of phenylalanine in the bloodstream, thereby reducing the toxic effects of of this amino acid. Normal serum concentrations of phenylalanine are 100 micomolar, while elevated (toxic) levels are typically >1200 micromolar. Individuals with a deficiency in tetrahydrobiopterin are not able to efficiently convert phenylalanine to tyrosine. The excess levels provided by tetrahydrobiopterin supplementation help improve enzyme efficiency. As a co-factor for tyrosine hydroxylase, BH4 facilitates the conversion of tyrosine to L-dopa while as a co-factor for tryptophan hydroxylase, BH4 allows the conversion of tryptophan to 5-hydroxytryptophan, which is then converted to serotonin.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 250-255 °C (hydrochloride salt) Not Available
water solubility >20 mg/mL (dichloride salt) Not Available
logP -1.7 Not Available
Predicted Properties
Property Value Source
water solubility 2.21e+00 g/l ALOGPS
logP -1.7 ALOGPS
logP -2.7 ChemAxon
logS -2 ALOGPS
pKa (strongest acidic) 10.01 ChemAxon
pKa (strongest basic) 3.58 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 6 ChemAxon
polar surface area 132 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 68.43 ChemAxon
polarizability 23.4 ChemAxon
药物相互作用
食物相互作用
Not Available

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