创建日期
2005-11-16 15:48:42 UTC
更新日期
2021-09-14 15:15:56 UTC
二级访问
HMDB0000787
HMDB0002154
HMDB00027
HMDB0059658
HMDB00787
HMDB02154
HMDB59658
描述
Tetrahydrobiopterin (CAS: 17528-72-2), also known as BH4, is an essential cofactor in the synthesis of neurotransmitters and nitric oxide (PMID: 16946131). In fact, it is used by all three human nitric-oxide synthases (NOS) eNOS, nNOS, and iNOS as well as the enzyme glyceryl-ether monooxygenase. It is also essential in the conversion of phenylalanine into tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine into L-dopa by the enzyme tyrosine hydroxylase; and the conversion of tryptophan into 5-hydroxytryptophan via tryptophan hydroxylase. Specifically, tetrahydrobiopterin is a cofactor for tryptophan 5-hydroxylase 1, tyrosine 3-monooxygenase, and phenylalanine hydroxylase, all of which are essential for the formation of the neurotransmitters dopamine, noradrenaline, and adrenaline. Tetrahydrobiopterin has been proposed to be involved in the promotion of neurotransmitter release in the brain and the regulation of human melanogenesis. A defect in BH4 production and/or a defect in the enzyme dihydropteridine reductase (DHPR) causes phenylketonuria type IV, as well as dopa-responsive dystonias. BH4 is also implicated in Parkinson's disease, Alzheimer's disease, and depression. Tetrahydrobiopterin is present in probably every cell or tissue of higher animals. On the other hand, most bacteria, fungi and plants do not synthesize tetrahydrobiopterin (Wikipedia).
同义词
1:(-)-(6R)-2-Amino-6-((1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinone
2:(6R)-L-Erythro-5,6,7,8-tetrahydrobiopterin
3:(6R)-L-Erythro-tetrahydrobiopterin
4:2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1H)-pteridinone
5:5,6,7,8-Tetrahydrobiopterin
6:6R-5,6,7,8-Tetrahydrobiopterin
7:6R-BH4
8:6R-L-5,6,7,8-Tetrahydrobiopterin
9:R-THBP
10:Sapropterina
11:Sapropterinum
12:Tetrahydrobiopterin
13:5,6,7,8-erythro-Tetrahydrobiopterin
14:5,6,7,8-tetrahydro-L-Erythrobiopterin
15:5,6,7,8-Tetrahydrobiopterin, (S-(r*,s*))-isomer
16:5,6,7,8-Tetrahydrodictyopterin
17:6R-L-erythro-5,6,7,8-Tetrahydrobiopterin
18:BPH4
19:D-threo-Tetrahydrobiopterin
20:THBP
21:Kuvan
22:Phenylalanine hydroxylase cofactor
23:Sapropterin dihydrochloride
24:tetrahydro-6-Biopterin
25:2',4',5'-Trihydroxybutyrophenone
26:Sapropterin
27:Trihydroxybutyrophenone
28:1-Butanone, 1-(2,4,5-trihydroxyphenyl)
29:2,4,5-Trihydroxybutyrophenone
30:(6R)-5,6,7,8-Tetrahydro-L-biopterin
31:(6R)-5,6,7,8-Tetrahydrobiopterin
32:(6R)-Tetrahydrobiopterin
33:2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinone
34:6R-Tetrahydro-L-biopterin
35:6beta-5,6,7,8-Tetrahydro-L-biopterin
36:6β-5,6,7,8-Tetrahydro-L-biopterin
37:L-erythro-Tetrahydrobiopterin
38:(6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone
化学名称
(6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-1,4,5,6,7,8-hexahydropteridin-4-one
代谢物结构字符串
[H][C@@]1(CNC2=C(N1)C(=O)N=C(N)N2)[C@@H](O)[C@H](C)O
inchi标识符
InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,4+,6-/m0/s1
印记键
FNKQXYHWGSIFBK-RPDRRWSUSA-N
分类学
description: belongs to the class of organic compounds known as biopterins and derivatives. These are coenzymes containing a 2-amino-pteridine-4-one derivative. They are mainly synthesized in several parts of the body, including the pineal gland.
description:Biopterins and derivatives
kingdom:Organic compounds
super_class:Organoheterocyclic compounds
class:Pteridines and derivatives
sub_class:Pterins and derivatives
molecular_framework:Aromatic heteropolycyclic compounds
1:1,2-aminoalcohols
2:1,2-diols
3:1,3-aminoalcohols
4:Aminopyrimidines and derivatives
5:Azacyclic compounds
6:Heteroaromatic compounds
7:Hydrocarbon derivatives
8:Organic oxides
9:Organopnictogen compounds
10:Primary amines
11:Pyrimidones
12:Secondary alcohols
13:Secondary alkylarylamines
14:Vinylogous amides
15:1,2-aminoalcohol
16:1,2-diol
17:1,3-aminoalcohol
18:Alcohol
19:Amine
20:Aminopyrimidine
21:Aromatic heteropolycyclic compound
22:Azacycle
23:Biopterin
24:Heteroaromatic compound
25:Hydrocarbon derivative
26:Organic nitrogen compound
27:Organic oxide
28:Organic oxygen compound
29:Organonitrogen compound
30:Organooxygen compound
31:Organopnictogen compound
32:Primary amine
33:Pyrimidine
34:Pyrimidone
35:Secondary alcohol
36:Secondary aliphatic/aromatic amine
37:Secondary amine
38:Vinylogous amide
39:5,6,7,8-tetrahydrobiopterin
40:Coenzymes
本体论
term:Physiological effect
definition:The effect on an organism physiology, resulting from its exposure to a chemical.
parent_id:
level:1
type:parent
term:Health effect
definition:A health condition or observation associated with a stimuli or with a biological activity of a chemical.
parent_id:7693
*level:2
type:parent
term:Health condition
definition:A health effect that consists on short or long-term disease, condition, disorder, syndrome or constant abnormality.
parent_id:7694
**level:3
type:parent
term:Septic shock
definition:
parent_id:7695
***level:4
type:child
synonym:Endotoxic shock
term:Epilepsy
definition:A brain disease that is characterized by the occurrance of at least two unprovoked seizures resulting from a persistent epileptogenic abnormality of the brain that is able to spontaneously generate paroxysmal activity and typically manifested by sudden brief episodes of altered or diminished consciousness, involuntary movements, or convulsions. (do).
parent_id:7695
***level:4
type:child
synonym:Epileptic spasms
term:Cardiac disorders
definition:Any disorder that affects the heart.
parent_id:7695
***level:4
type:parent
term:Disposition
definition:A concept that describes the origin of a chemical, its location within an organism, or its route of exposure.
parent_id:
level:1
type:parent
term:Source
definition:Natural or synthetic origin of a chemical.
parent_id:7724
*level:2
type:parent
term:Endogenous
definition:
parent_id:7735
**level:3
type:child
term:Biological location
definition:The physiological origin within an organism, including anatomical compnents, biofluids and excreta.
parent_id:7724
*level:2
type:parent
term:Tissue and substructures
definition:An anatomical organizational level including multiple cells yet not comprising a complete organ .
parent_id:7725
**level:3
type:parent
term:All tissues
definition:All tissues in the body of the organism.
parent_id:7729
***level:4
type:child
term:Biofluid and excreta
definition:A liquid, semi-solid or solid material originating in the body.
parent_id:7725
**level:3
type:parent
term:Feces
definition:The material discharged from the bowel during defecation. It consists of undigested food, intestinal mucus, epithelial cells, and bacteria.
parent_id:7731
***level:4
type:child
synonym:Fecal
synonym:Stool
synonym:Faecal
synonym:Faeces
term:Blood
definition:A liquid tissue with the primary function of transporting oxygen and carbon dioxide (nci). it supplies the tissues with nutrients, removes waste products, and contains various components of the immune system defending the body against infection.
parent_id:7731
***level:4
type:child
term:Cerebrospinal fluid
definition:The fluid that is contained within the brain ventricles, the subarachnoid space and the central canal of the spinal cord. (nci).
parent_id:7731
***level:4
type:child
synonym:Csf
term:Subcellular
definition:An anatomical organizational level including a component within a biological cell .
parent_id:7725
**level:3
type:parent
term:Nucleus
definition:A body within the cell, surrounded by a membrane, within which lie the chromosomes, one or more nucleoli, combined with proteins, and exhibits mitosis. (NCI)
parent_id:7730
***level:4
type:child
synonym:Cell nucleus
synonym:Nucleic
term:Mitochondria
definition:
parent_id:7730
***level:4
type:child
term:Cytoplasm
definition:The portion of the cell contained within the plasma membrane but excluding the nucleus.
parent_id:7730
***level:4
type:child
synonym:Cytoplasma
term:Process
definition:Biological or chemical events, or a series thereof, leading to a known function or end-product.
parent_id:
level:1
type:parent
term:Naturally occurring process
definition:Naturally-occurring molecular events or a series thereof, leading to a known function or end-product.
parent_id:7659
*level:2
type:parent
term:Biological process
definition:Biological or chemical events or a series thereof, leading to a known function or end-product within an organism.
parent_id:7660
**level:3
type:parent
term:Biochemical pathway
definition:A linked series of chemical reactions that occur in a defined order within or between organism cells, and lead to a known function or end product.
parent_id:7661
***level:4
type:parent
实验性质
1:
kind:melting_point
value:250 - 255 °C (hydrochloride salt)
source:
预测性质
1:
kind:logp
value:-1.66
source:ALOGPS
2:
kind:logs
value:-2.04
source:ALOGPS
3:
kind:solubility
value:2.03 g/L
source:ALOGPS
4:
kind:logp
value:-2.7
source:ChemAxon
5:
kind:pka_strongest_acidic
value:13.52
source:ChemAxon
6:
kind:pka_strongest_basic
value:1.58
source:ChemAxon
7:
kind:iupac
value:(6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-1,4,5,6,7,8-hexahydropteridin-4-one
source:ChemAxon
8:
kind:average_mass
value:241.2471
source:ChemAxon
9:
kind:mono_mass
value:241.117489371
source:ChemAxon
10:
kind:smiles
value:[H][C@@]1(CNC2=C(N1)C(=O)N=C(N)N2)[C@@H](O)[C@H](C)O
source:ChemAxon
11:
kind:formula
value:C9H15N5O3
source:ChemAxon
12:
kind:inchi
value:InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,4+,6-/m0/s1
source:ChemAxon
13:
kind:inchikey
value:FNKQXYHWGSIFBK-RPDRRWSUSA-N
source:ChemAxon
14:
kind:polar_surface_area
value:132
source:ChemAxon
15:
kind:refractivity
value:68.43
source:ChemAxon
16:
kind:polarizability
value:23.67
source:ChemAxon
17:
kind:rotatable_bond_count
value:2
source:ChemAxon
18:
kind:acceptor_count
value:8
source:ChemAxon
19:
kind:donor_count
value:6
source:ChemAxon
20:
kind:physiological_charge
value:0
source:ChemAxon
21:
kind:formal_charge
value:0
source:ChemAxon
22:
kind:number_of_rings
value:2
source:ChemAxon
23:
kind:bioavailability
value:Yes
source:ChemAxon
24:
kind:rule_of_five
value:No
source:ChemAxon
25:
kind:ghose_filter
value:No
source:ChemAxon
26:
kind:veber_rule
value:No
source:ChemAxon
27:
kind:mddr_like_rule
value:No
source:ChemAxon
生物学性质
1:
cellular:(1):Nucleus
2:
biospecimen:(1):Blood
biospecimen:(2):Cerebrospinal Fluid (CSF)
biospecimen:(3):Feces
3:
tissue:(1):All Tissues
4:
[1]:
name:Alkaptonuria
smpdb_id:SMP00169
kegg_map_id:
[2]:
name:Arginine and proline metabolism
smpdb_id:
kegg_map_id:map00330
[3]:
name:Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)
smpdb_id:SMP00362
kegg_map_id:
[4]:
name:Aromatic L-Aminoacid Decarboxylase Deficiency
smpdb_id:SMP00170
kegg_map_id:
[5]:
name:Creatine deficiency, guanidinoacetate methyltransferase deficiency
smpdb_id:SMP00504
kegg_map_id:
[6]:
name:Disulfiram Action Pathway
smpdb_id:SMP00429
kegg_map_id:
[7]:
name:Dopa-responsive dystonia
smpdb_id:SMP00486
kegg_map_id:
[8]:
name:Dopamine beta-hydroxylase deficiency
smpdb_id:SMP00498
kegg_map_id:
[9]:
name:Doxorubicin Metabolism Pathway
smpdb_id:SMP00650
kegg_map_id:
[10]:
name:Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)
smpdb_id:SMP00188
kegg_map_id:
[11]:
name:Hawkinsinuria
smpdb_id:SMP00190
kegg_map_id:
[12]:
name:Hyperornithinemia with gyrate atrophy (HOGA)
smpdb_id:SMP00505
kegg_map_id:
[13]:
name:Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]
smpdb_id:SMP00506
kegg_map_id:
[14]:
name:Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
smpdb_id:SMP00487
kegg_map_id:
[15]:
name:Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
smpdb_id:SMP00488
kegg_map_id:
[16]:
name:Hyperphenylalaninemia due to dhpr-deficiency
smpdb_id:SMP00489
kegg_map_id:
[17]:
name:Hyperprolinemia Type I
smpdb_id:SMP00361
kegg_map_id:
[18]:
name:Hyperprolinemia Type II
smpdb_id:SMP00360
kegg_map_id:
[19]:
name:L-arginine:glycine amidinotransferase deficiency
smpdb_id:SMP00507
kegg_map_id:
[20]:
name:Monoamine oxidase-a deficiency (MAO-A)
smpdb_id:SMP00533
kegg_map_id:
[21]:
name:Ornithine Aminotransferase Deficiency (OAT Deficiency)
smpdb_id:SMP00363
kegg_map_id:
[22]:
name:Phenylalanine and Tyrosine Metabolism
smpdb_id:SMP00008
kegg_map_id:map00360
[23]:
name:Phenylketonuria
smpdb_id:SMP00206
kegg_map_id:
[24]:
name:Prolidase Deficiency (PD)
smpdb_id:SMP00207
kegg_map_id:
[25]:
name:Prolinemia Type II
smpdb_id:SMP00208
kegg_map_id:
[26]:
name:Pterine Biosynthesis
smpdb_id:SMP00005
kegg_map_id:map00790
[27]:
name:Segawa syndrome
smpdb_id:SMP00490
kegg_map_id:
[28]:
name:Sepiapterin reductase deficiency
smpdb_id:SMP00491
kegg_map_id:
[29]:
name:Tryptophan metabolism
smpdb_id:
kegg_map_id:map00380
[30]:
name:Tyrosine hydroxylase deficiency
smpdb_id:SMP00497
kegg_map_id:
[31]:
name:Tyrosine metabolism
smpdb_id:
kegg_map_id:map00350
[32]:
name:Tyrosine metabolism
smpdb_id:
kegg_map_id:map00350
[33]:
name:Tyrosinemia Type 2 (or Richner-Hanhart syndrome)
smpdb_id:SMP00369
kegg_map_id:
[34]:
name:Tyrosinemia Type 3 (TYRO3)
smpdb_id:SMP00370
kegg_map_id:
[35]:
name:Tyrosinemia Type I
smpdb_id:SMP00218
kegg_map_id:
[36]:
name:Tyrosinemia, transient, of the newborn
smpdb_id:SMP00494
kegg_map_id:
正常浓度
1:
biospecimen:Blood
concentration_value:0.0110 +/- 0.0008
concentration_units:uM
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
2:
biospecimen:Blood
concentration_value:0.0093 +/- 0.0005
concentration_units:uM
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
3:
biospecimen:Cerebrospinal Fluid (CSF)
concentration_value:0.026 (0.014-0.038)
concentration_units:uM
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
异常浓度
1:
biospecimen:Blood
concentration_value:0.16 (0.0-5.8)
concentration_units:uM
patient_age:Adult (>18 years old)
patient_sex:Both
patient_information:Septic shock
2:
biospecimen:Blood
concentration_value:1.2 (0.8-14.9)
concentration_units:uM
patient_age:Adult (>18 years old)
patient_sex:Both
patient_information:Septic shock
3:
biospecimen:Blood
concentration_value:0.0099 +/- 0.0008
concentration_units:uM
patient_age:Adult (>18 years old)
patient_sex:Both
patient_information:Smoking
4:
biospecimen:Blood
concentration_value:0.0044 +/- 0.0007
concentration_units:uM
patient_age:Adult (>18 years old)
patient_sex:Both
patient_information:Myocardial infarction
5:
biospecimen:Cerebrospinal Fluid (CSF)
concentration_value:14400.0
concentration_units:uM
patient_age:Newborn (0-30 days old)
patient_sex:Both
patient_information:Generalized seizures
6:
biospecimen:Feces
concentration_value:
concentration_units:
patient_age:Children (1-13 years old)
patient_sex:Both
patient_information:Enthesitis-related arthritis
疾病参考
1:
name:Septic shock
omim_id:
[1]:
reference_text:Kaufmann I, Hoelzl A, Schliephake F, Hummel T, Chouker A, Lysenko L, Peter K, Thiel M: Effects of adenosine on functions of polymorphonuclear leukocytes from patients with septic shock. Shock. 2007 Jan;27(1):25-31.
pubmed_id:17172976
[2]:
reference_text:Galley HF, Le Cras AE, Yassen K, Grant IS, Webster NR: Circulating tetrahydrobiopterin concentrations in patients with septic shock. Br J Anaesth. 2001 Apr;86(4):578-80.
pubmed_id:11573638
[3]:
reference_text:Jabs CM, Sigurdsson GH, Neglen P: Plasma levels of high-energy compounds compared with severity of illness in critically ill patients in the intensive care unit. Surgery. 1998 Jul;124(1):65-72.
pubmed_id:9663253
2:
name:Smoking
omim_id:
[1]:
reference_text:Ruppert T, Scherer G, Tricker AR, Adlkofer F: trans,trans-muconic acid as a biomarker of non-occupational environmental exposure to benzene. Int Arch Occup Environ Health. 1997;69(4):247-51.
pubmed_id:9137998
[2]:
reference_text:Zuccaro P, Altieri I, Rosa M, Passa AR, Pichini S, Ricciarello G, Pacifici R: Determination of nicotine and four metabolites in the serum of smokers by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 1993 Nov 24;621(2):257-61.
pubmed_id:8294547
[3]:
reference_text:Ueda S, Matsuoka H, Miyazaki H, Usui M, Okuda S, Imaizumi T: Tetrahydrobiopterin restores endothelial function in long-term smokers. J Am Coll Cardiol. 2000 Jan;35(1):71-5.
pubmed_id:10636262
[4]:
reference_text:Carmella SG, La Voie EJ, Hecht SS: Quantitative analysis of catechol and 4-methylcatechol in human urine. Food Chem Toxicol. 1982 Oct;20(5):587-90.
pubmed_id:6890513
[5]:
reference_text:Moyer TP, Charlson JR, Enger RJ, Dale LC, Ebbert JO, Schroeder DR, Hurt RD: Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem. 2002 Sep;48(9):1460-71.
pubmed_id:12194923
[6]:
reference_text:Chen HJ, Wu CF, Huang JL: Measurement of urinary excretion of 5-hydroxymethyluracil in human by GC/NICI/MS: correlation with cigarette smoking, urinary TBARS and etheno DNA adduct. Toxicol Lett. 2005 Mar 15;155(3):403-10.
pubmed_id:15649624
[7]:
reference_text:Massadeh AM, Gharaibeh AA, Omari KW: A single-step extraction method for the determination of nicotine and cotinine in Jordanian smokers' blood and urine samples by RP-HPLC and GC-MS. J Chromatogr Sci. 2009 Feb;47(2):170-7.
pubmed_id:19222926
[8]:
reference_text:Orhan H, Coolen S, Meerman JH: Quantification of urinary o,o'-dityrosine, a biomarker for oxidative damage to proteins, by high performance liquid chromatography with triple quadrupole tandem mass spectrometry. A comparison with ion-trap tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):104-8.
pubmed_id:15878312
[9]:
reference_text:Schettgen T, Musiol A, Kraus T: Simultaneous determination of mercapturic acids derived from ethylene oxide (HEMA), propylene oxide (2-HPMA), acrolein (3-HPMA), acrylamide (AAMA) and N,N-dimethylformamide (AMCC) in human urine using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2008 Sep;22(17):2629-38. doi: 10.1002/rcm.3659.
pubmed_id:18666198
[10]:
reference_text:Li N, Jia X, Chen CY, Blumberg JB, Song Y, Zhang W, Zhang X, Ma G, Chen J: Almond consumption reduces oxidative DNA damage and lipid peroxidation in male smokers. J Nutr. 2007 Dec;137(12):2717-22.
pubmed_id:18029489
[11]:
reference_text:Malkawi AH, Al-Ghananeem AM, de Leon J, Crooks PA: Nicotine exposure can be detected in cerebrospinal fluid of active and passive smokers. J Pharm Biomed Anal. 2009 Jan 15;49(1):129-32. doi: 10.1016/j.jpba.2008.10.003. Epub 2008 Oct 15.
pubmed_id:19036546
[12]:
reference_text:Geigy Scientific Tables, 8th Rev edition, pp. 165-177. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.
pubmed_id:
3:
name:Myocardial infarction
omim_id:
[1]:
reference_text:Wannemacher RW Jr, Klainer AS, Dinterman RE, Beisel WR: The significance and mechanism of an increased serum phenylalanine-tyrosine ratio during infection. Am J Clin Nutr. 1976 Sep;29(9):997-1006.
pubmed_id:822705
[2]:
reference_text:Mocatta TJ, Pilbrow AP, Cameron VA, Senthilmohan R, Frampton CM, Richards AM, Winterbourn CC: Plasma concentrations of myeloperoxidase predict mortality after myocardial infarction. J Am Coll Cardiol. 2007 May 22;49(20):1993-2000. Epub 2007 May 4.
pubmed_id:17512353
[3]:
reference_text:Yada T, Kaji S, Akasaka T, Mochizuki S, Ogasawara Y, Tanemoto K, Yoshida K, Kajiya F: Changes of asymmetric dimethylarginine, nitric oxide, tetrahydrobiopterin, and oxidative stress in patients with acute myocardial infarction by medical treatments. Clin Hemorheol Microcirc. 2007;37(3):269-76.
pubmed_id:17726257
4:
name:Epilepsy
omim_id:
[1]:
reference_text:Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24.
pubmed_id:14992292
[2]:
reference_text:Cady EB, Lorek A, Penrice J, Reynolds EO, Iles RA, Burns SP, Coutts GA, Cowan FM: Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Med. 1994 Dec;32(6):764-7.
pubmed_id:7869898
[3]:
reference_text:Perosa SR, Porcionatto MA, Cukiert A, Martins JR, Amado D, Nader HB, Cavalheiro EA, Leite JP, Naffah-Mazzacoratti MG: Extracellular matrix components are altered in the hippocampus, cortex, and cerebrospinal fluid of patients with mesial temporal lobe epilepsy. Epilepsia. 2002;43 Suppl 5:159-61.
pubmed_id:12121313
[4]:
reference_text:Spanaki MV, Siegel H, Kopylev L, Fazilat S, Dean A, Liow K, Ben-Menachem E, Gaillard WD, Theodore WH: The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism. Neurology. 1999 Oct 22;53(7):1518-22.
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reference_text:Rating D, Siemes H, Loscher W: Low CSF GABA concentration in children with febrile convulsions, untreated epilepsy, and meningitis. J Neurol. 1983;230(4):217-25.
pubmed_id:6198481
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reference_text:Botez MI, Young SN: Effects of anticonvulsant treatment and low levels of folate and thiamine on amine metabolites in cerebrospinal fluid. Brain. 1991 Feb;114 ( Pt 1A):333-48.
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reference_text:Kobayashi K, Koide Y, Yoshino K, Shohmori T: [P-hydroxyphenylacetic acid concentrations in cerebrospinal fluid]. No To Shinkei. 1982 Aug;34(8):769-74.
pubmed_id:7126379
[8]:
reference_text:Czarnecka J, Cieslak M, Michal K: Application of solid phase extraction and high-performance liquid chromatography to qualitative and quantitative analysis of nucleotides and nucleosides in human cerebrospinal fluid. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Aug 5;822(1-2):85-90.
pubmed_id:15993662
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reference_text:Shaywitz BA, Cohen DJ, Bowers MB: Reduced cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in children with epilepsy. Neurology. 1975 Jan;25(1):72-9.
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综合参考
Steven S. Gross, "Blocking utilization of tetrahydrobiopterin to block induction of nitric oxide synthesis." U.S. Patent US5502050, issued October, 1984.
一般参考
1:
protein_accession:HMDBP00087
name:Tyrosinase
uniprot_id:P14679
gene_name:TYR
protein_type:Unknown
2:
protein_accession:HMDBP00273
name:Tyrosine 3-monooxygenase
uniprot_id:P07101
gene_name:TH
protein_type:Enzyme
3:
protein_accession:HMDBP00280
name:Phenylalanine-4-hydroxylase
uniprot_id:P00439
gene_name:PAH
protein_type:Enzyme
4:
protein_accession:HMDBP00435
name:6-pyruvoyl tetrahydrobiopterin synthase
uniprot_id:Q03393
gene_name:PTS
protein_type:Unknown
5:
protein_accession:HMDBP00436
name:Sepiapterin reductase
uniprot_id:P35270
gene_name:SPR
protein_type:Enzyme
6:
protein_accession:HMDBP00469
name:Tryptophan 5-hydroxylase 1
uniprot_id:P17752
gene_name:TPH1
protein_type:Enzyme
7:
protein_accession:HMDBP00471
name:Tryptophan 5-hydroxylase 2
uniprot_id:Q8IWU9
gene_name:TPH2
protein_type:Enzyme
8:
protein_accession:HMDBP00545
name:Dihydropteridine reductase
uniprot_id:P09417
gene_name:QDPR
protein_type:Unknown
9:
protein_accession:HMDBP00926
name:Nitric oxide synthase, inducible
uniprot_id:P35228
gene_name:NOS2
protein_type:Unknown
10:
protein_accession:HMDBP00928
name:Nitric oxide synthase, brain
uniprot_id:P29475
gene_name:NOS1
protein_type:Unknown
11:
protein_accession:HMDBP00929
name:Nitric oxide synthase, endothelial
uniprot_id:P29474
gene_name:NOS3
protein_type:Unknown
12:
protein_accession:HMDBP00938
name:GTP cyclohydrolase 1
uniprot_id:P30793
gene_name:GCH1
protein_type:Unknown
13:
protein_accession:HMDBP01961
name:GTP cyclohydrolase 1 feedback regulatory protein
uniprot_id:P30047
gene_name:GCHFR
protein_type:Unknown
14:
protein_accession:HMDBP02872
name:Pterin-4-alpha-carbinolamine dehydratase
uniprot_id:P61457
gene_name:PCBD1
protein_type:Enzyme
15:
protein_accession:HMDBP10682
name:Calcium-calmodulin independent nitric oxide synthase iNOS protein
uniprot_id:Q9UM94
gene_name:
protein_type:Enzyme
蛋白质结合
1:
reference_text:Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, Shimadzu M, Hyland K, Trugman JM: Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol. 1998 Jul;44(1):10-6.
pubmed_id:9667588
2:
reference_text:Curtius HC, Heintel D, Ghisla S, Kuster T, Leimbacher W, Niederwieser A: Tetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved. Eur J Biochem. 1985 May 2;148(3):413-9.
pubmed_id:3888618
3:
reference_text:Galley HF, Le Cras AE, Yassen K, Grant IS, Webster NR: Circulating tetrahydrobiopterin concentrations in patients with septic shock. Br J Anaesth. 2001 Apr;86(4):578-80.
pubmed_id:11573638
4:
reference_text:Kuhn DM, Geddes TJ: Tetrahydrobiopterin prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide. Mol Pharmacol. 2003 Oct;64(4):946-53.
pubmed_id:14500751
5:
reference_text:Takikawa S, Curtius HC, Redweik U, Leimbacher W, Ghisla S: Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver. Eur J Biochem. 1986 Dec 1;161(2):295-302.
pubmed_id:3536512
6:
reference_text:Walter R, Kaufmann PA, Buck A, Berthold T, Wyss C, von Schulthess GK, Schaffner A, Schoedon G: Tetrahydrobiopterin increases myocardial blood flow in healthy volunteers: a double-blind, placebo-controlled study. Swiss Med Wkly. 2001 Feb 24;131(7-8):91-4.
pubmed_id:11416883
7:
reference_text:Hyland K, Gunasekara RS, Munk-Martin TL, Arnold LA, Engle T: The hph-1 mouse: a model for dominantly inherited GTP-cyclohydrolase deficiency. Ann Neurol. 2003;54 Suppl 6:S46-8.
pubmed_id:12891653
8:
reference_text:Leeming RJ, Blair JA, Melikian V, O'Gorman DJ: Biopterin derivatives in human body fluids and tissues. J Clin Pathol. 1976 May;29(5):444-51.
pubmed_id:932231
9:
reference_text:Schallreuter KU, Moore J, Wood JM, Beazley WD, Peters EM, Marles LK, Behrens-Williams SC, Dummer R, Blau N, Thony B: Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes? J Invest Dermatol. 2001 Jan;116(1):167-74.
pubmed_id:11168813
10:
reference_text:Dhondt JL, Cotton RG, Danks DM: Liver enzyme activities in hyperphenylalaninaemia due to a defective synthesis of tetrahydrobiopterin. J Inherit Metab Dis. 1985;8(2):47-8.
pubmed_id:3939528
11:
reference_text:Sawabe K, Suetake Y, Nakanishi N, Wakasugi KO, Hasegawa H: Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes; direct uptake and indirect uptake mediated by a methotrexate-sensitive process. Mol Genet Metab. 2005 Dec;86 Suppl 1:S133-8. Epub 2005 Sep 13.
pubmed_id:16165391
12:
reference_text:Koch R, Moseley KD, Moats R, Yano S, Matalon R, Guttler F: Danger of high-protein dietary supplements to persons with hyperphenylalaninaemia. J Inherit Metab Dis. 2003;26(4):339-42.
pubmed_id:12971421
13:
reference_text:Cady EB, Lorek A, Penrice J, Reynolds EO, Iles RA, Burns SP, Coutts GA, Cowan FM: Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Med. 1994 Dec;32(6):764-7.
pubmed_id:7869898
14:
reference_text:Matter H, Kumar HS, Fedorov R, Frey A, Kotsonis P, Hartmann E, Frohlich LG, Reif A, Pfleiderer W, Scheurer P, Ghosh DK, Schlichting I, Schmidt HH: Structural analysis of isoform-specific inhibitors targeting the tetrahydrobiopterin binding site of human nitric oxide synthases. J Med Chem. 2005 Jul 28;48(15):4783-92.
pubmed_id:16033258
15:
reference_text:Kaufman S, Kapatos G, Rizzo WB, Schulman JD, Tamarkin L, Van Loon GR: Tetrahydropterin therapy for hyperphenylalaninemia caused by defective synthesis of tetrahydrobiopterin. Ann Neurol. 1983 Sep;14(3):308-15.
pubmed_id:6139056
16:
reference_text:Spaapen LJ, Bakker JA, Velter C, Loots W, Rubio-Gozalbo ME, Forget PP, Dorland L, De Koning TJ, Poll-The BT, Ploos van Amstel HK, Bekhof J, Blau N, Duran M: Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates. J Inherit Metab Dis. 2001 Jun;24(3):352-8.
pubmed_id:11486900
17:
reference_text:Toda Y, Mori K, Hashimoto T, Miyazaki M, Nozaki S, Watanabe Y, Kuroda Y, Kagami S: Administration of secretin for autism alters dopamine metabolism in the central nervous system. Brain Dev. 2006 Mar;28(2):99-103. Epub 2005 Sep 15.
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18:
reference_text:Moens AL, Kass DA: Tetrahydrobiopterin and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2439-44. Epub 2006 Aug 31.
pubmed_id:16946131
19:
reference_text:Komori H, Matsuishi T, Yamada S, Yamashita Y, Ohtaki E, Kato H: Cerebrospinal fluid biopterin and biogenic amine metabolites during oral R-THBP therapy for infantile autism. J Autism Dev Disord. 1995 Apr;25(2):183-93.
pubmed_id:7559284
20:
reference_text:Kaufman S: Biopterin-responsive hyperphenylalaninemia. J Nutr Sci Vitaminol (Tokyo). 1992;Spec No:601-6.
pubmed_id:1297822
21:
reference_text:Sanford M, Keating GM: Spotlight on sapropterin in primary hyperphenylalaninemia. BioDrugs. 2009;23(3):201-2. doi: 10.2165/00063030-200923030-00007.
pubmed_id:19627172
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reference_text:MacDonald A, Ahring K, Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC, van Rijn M, Belanger-Quintana A: Adjusting diet with sapropterin in phenylketonuria: what factors should be considered? Br J Nutr. 2011 Jul;106(2):175-82. doi: 10.1017/S0007114511000298.
pubmed_id:21466737
23:
reference_text:Burton BK, Nowacka M, Hennermann JB, Lipson M, Grange DK, Chakrapani A, Trefz F, Dorenbaum A, Imperiale M, Kim SS, Fernhoff PM: Safety of extended treatment with sapropterin dihydrochloride in patients with phenylketonuria: results of a phase 3b study. Mol Genet Metab. 2011 Aug;103(4):315-22. doi: 10.1016/j.ymgme.2011.03.020. Epub 2011 Mar 31.
pubmed_id:21646032
24:
reference_text:Utz JR, Lorentz CP, Markowitz D, Rudser KD, Diethelm-Okita B, Erickson D, Whitley CB: START, a double blind, placebo-controlled pharmacogenetic test of responsiveness to sapropterin dihydrochloride in phenylketonuria patients. Mol Genet Metab. 2012 Feb;105(2):193-7. doi: 10.1016/j.ymgme.2011.10.014. Epub 2011 Oct 29.
pubmed_id:22112818
25:
reference_text:Gordon P, Thomas JA, Suter R, Jurecki E: Evolving patient selection and clinical benefit criteria for sapropterin dihydrochloride (Kuvan(R)) treatment of PKU patients. Mol Genet Metab. 2012 Apr;105(4):672-6. doi: 10.1016/j.ymgme.2011.12.023. Epub 2012 Jan 8.
pubmed_id:22310224
26:
reference_text:Leuret O, Barth M, Kuster A, Eyer D, de Parscau L, Odent S, Gilbert-Dussardier B, Feillet F, Labarthe F: Efficacy and safety of BH4 before the age of 4 years in patients with mild phenylketonuria. J Inherit Metab Dis. 2012 Nov;35(6):975-81. doi: 10.1007/s10545-012-9464-3. Epub 2012 Mar 3.
pubmed_id:22388642
27:
reference_text:Ziesch B, Weigel J, Thiele A, Mutze U, Rohde C, Ceglarek U, Thiery J, Kiess W, Beblo S: Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life. J Inherit Metab Dis. 2012 Nov;35(6):983-92. doi: 10.1007/s10545-012-9458-1. Epub 2012 Mar 6.
pubmed_id:22391997
28:
reference_text:Cunningham A, Bausell H, Brown M, Chapman M, DeFouw K, Ernst S, McClure J, McCune H, O'Steen D, Pender A, Skrabal J, Wessel A, Jurecki E, Shediac R, Prasad S, Gillis J, Cederbaum S: Recommendations for the use of sapropterin in phenylketonuria. Mol Genet Metab. 2012 Jul;106(3):269-76. doi: 10.1016/j.ymgme.2012.04.004. Epub 2012 Apr 13.
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reference_text:Shintaku H, Ohwada M: Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan. Brain Dev. 2013 May;35(5):406-10. doi: 10.1016/j.braindev.2012.06.010. Epub 2012 Jul 24.
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reference_text:Somaraju UR, Merrin M: Sapropterin dihydrochloride for phenylketonuria. Cochrane Database Syst Rev. 2012 Dec 12;12:CD008005. doi: 10.1002/14651858.CD008005.pub3.
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reference_text:Gokmen Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC, van Rijn M, Ahring K, Belanger-Quintana A, MacDonald A, Dokoupil K: Use of sapropterin in the management of phenylketonuria: seven case reports. Mol Genet Metab. 2013 Feb;108(2):109-11. doi: 10.1016/j.ymgme.2012.11.012. Epub 2012 Nov 28.
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32:
reference_text:Thiele AG, Weigel JF, Ziesch B, Rohde C, Mutze U, Ceglarek U, Thiery J, Muller AS, Kiess W, Beblo S: Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH(4)). JIMD Rep. 2013;9:31-40. doi: 10.1007/8904_2012_176. Epub 2012 Oct 17.
pubmed_id:23430545
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reference_text:Cerone R, Andria G, Giovannini M, Leuzzi V, Riva E, Burlina A: Testing for tetrahydrobiopterin responsiveness in patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. Adv Ther. 2013 Mar;30(3):212-28. doi: 10.1007/s12325-013-0011-x. Epub 2013 Feb 20.
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reference_text:Keil S, Anjema K, van Spronsen FJ, Lambruschini N, Burlina A, Belanger-Quintana A, Couce ML, Feillet F, Cerone R, Lotz-Havla AS, Muntau AC, Bosch AM, Meli CA, Billette de Villemeur T, Kern I, Riva E, Giovannini M, Damaj L, Leuzzi V, Blau N: Long-term follow-up and outcome of phenylketonuria patients on sapropterin: a retrospective study. Pediatrics. 2013 Jun;131(6):e1881-8. doi: 10.1542/peds.2012-3291. Epub 2013 May 20.
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reference_text:Blau N: Sapropterin dihydrochloride for the treatment of hyperphenylalaninemias. Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1207-18. doi: 10.1517/17425255.2013.804064. Epub 2013 May 27.
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