- 同
- TPH
- 同
- TPH
WordNet
- an amino acid that occurs in proteins; is essential for growth and normal metabolism; a precursor of niacin (同)tryptophane
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/20 15:41:47」(JST)
[Wiki en表示]
| tryptophan 5-monooxygenase |
| Identifiers |
| EC number |
1.14.16.4 |
| CAS number |
9037-21-2 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
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| tryptophan hydroxylase 1 (tryptophan 5-monooxygenase) |
| Identifiers |
| Symbol |
TPH1 |
| Alt. symbols |
TPRH, TPH |
| Entrez |
7166 |
| HUGO |
12008 |
| OMIM |
191060 |
| PDB |
1MLW (RCSB PDB PDBe PDBj) |
| RefSeq |
NM_004179 |
| UniProt |
P17752 |
| Other data |
| Locus |
Chr. 11 p15.3-p14 |
| tryptophan hydroxylase 2 |
| Identifiers |
| Symbol |
TPH2 |
| Entrez |
121278 |
| HUGO |
20692 |
| OMIM |
607478 |
| RefSeq |
NM_173353 |
| UniProt |
Q8IWU9 |
| Other data |
| Locus |
Chr. 12 q15 |
|
Tryptophan hydroxylase (TPH) is an enzyme (EC 1.14.16.4) involved in the synthesis of the neurotransmitter serotonin. TPH catalyzes the following chemical reaction
- L-tryptophan + tetrahydrobiopterin + O2 5-Hydroxytryptophan + dihydrobiopterin + H2O
It employs one additional cofactor, iron.
Contents
- 1 Function
- 2 Isoforms
- 3 Additional images
- 4 References
- 5 Further reading
- 6 External links
Function
| Tryptophan |
{{{forward_enzyme}}} |
5-HTP |
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| {{{minor_forward_substrate(s)}}} |
{{{minor_forward_product(s)}}} |
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It is responsible for addition of the -HO group (hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin.
Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH) are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways.[1] Analogously to phenylalanine hydroxylase and tyrosine hydroxylase, this enzyme uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) and dioxygen as cofactors.[2]
In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect[citation needed] and inhibition of tryptophan hydroxylase (e.g. by p-Chlorophenylalanine) may precipitate depression.[3]
The activity of tryptophan hydroxylase (i.e. the rate at which it converts L-tryptophan into the serotonin precursor L-5-hydroxytryptophan) can be increased when it undergoes phosphorylation. Protein Kinase A, for example, can phosphorylate tryptophan hydroxylase, thus increasing its activity.
Isoforms
In humans, as well as in other mammals, there are two distinct TPH genes. In humans, these genes are located on chromosomes 11 and 12 and encode two different homologous enzymes TPH1 and TPH2 (sequence identity 71%).[4]
- TPH1 is mostly expressed in tissues that express serotonin (a neurotransmitter) in the periphery (skin, gut, pineal gland) but it is also expressed in the central nervous system.
- On the other hand, TPH2 is exclusively expressed in neuronal cell types and is the predominant isoform in the central nervous system.
Additional images
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The pathway for the synthesis of serotonin from tryptophan
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Metabolic pathway from tryptophan to serotonin
References
- ^ McKinney J, Teigen K, Frøystein NA, Salaün C, Knappskog PM, Haavik J, Martínez A (December 2001). "Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity". Biochemistry 40 (51): 15591–601. doi:10.1021/bi015722x. PMID 11747434.
- ^ "tetrahydrobiopterin". BH4 Databases. BH4.org. 2005.
- ^ Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC (October 2002). "Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin". Biochemistry 41 (42): 12569–74. doi:10.1021/bi026561f. PMID 12379098.
- ^ Walther DJ, Bader M (November 2003). "A unique central tryptophan hydroxylase isoform". Biochem. Pharmacol. 66 (9): 1673–80. doi:10.1016/S0006-2952(03)00556-2. PMID 14563478.
Further reading
- Friedman PA, Kappelman AH, Kaufman S (1972). "Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain". J. Biol. Chem. 247 (13): 4165–73. PMID 4402511.
- Hamon M, Bourgoin S, Artaud F, Glowinski J (1979). "The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium". J. Neurochem. 33 (5): 1031–42. doi:10.1111/j.1471-4159.1979.tb05239.x. PMID 315449.
- Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O (1970). "Enzymic studies on the biosynthesis of serotonin in mammalian brain". J. Biol. Chem. 245 (7): 1699–709. PMID 5309585.
- Jequier E, Robinson DS, Lovenberg W, Sjoerdsma A (1969). "Further studies on tryptophan hydroxylase in rat brainstem and beef pineal". Biochem. Pharmacol. 18 (5): 1071–81. doi:10.1016/0006-2952(69)90111-7. PMID 5789774.
- Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC (2002). "Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin". Biochemistry. 41 (42): 12569–74. doi:10.1021/bi026561f. PMID 12379098.
- Windahl MS, Petersen CR, Christensen, HEM, Harris P (2008). "Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate". Biochemistry. 47 (46): 12087–94. doi:10.1021/bi8015263. PMID 18937498.
External links
- Tryptophan Hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH)
See also tryptophan hydroxylase in Proteopedia
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Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
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| 1.14.11: 2-oxoglutarate |
- Prolyl hydroxylase
- Lysyl hydroxylase
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| 1.14.13: NADH or NADPH |
- Flavin-containing monooxygenase
- Nitric oxide synthase
- Cholesterol 7 alpha-hydroxylase
- Methane monooxygenase
- 3A4
- Lanosterol 14 alpha-demethylase
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| 1.14.14: reduced flavin or flavoprotein |
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| 1.14.15: reduced iron-sulfur protein |
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| 1.14.16: reduced pteridine (BH4 dependent) |
- Phenylalanine hydroxylase
- Tyrosine hydroxylase
- Tryptophan hydroxylase
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| 1.14.17: reduced ascorbate |
- Dopamine beta hydroxylase
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| 1.14.18-19: other |
- Tyrosinase
- Stearoyl-CoA desaturase-1
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| 1.14.99 - miscellaneous |
- Cyclooxygenase
- Heme oxygenase (HMOX1)
- Squalene monooxygenase
- 17A1
- 21A2
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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- Metabolism: amino acid metabolism
- neurotransmitter enzymes
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| monoamine |
| histidine → histamine |
| anabolism: |
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| catabolism: |
- Histamine N-methyltransferase
- Amine oxidase
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| tyrosine→dopamine→epinephrine |
| anabolism: |
- Tyrosine hydroxylase
- Aromatic L-amino acid decarboxylase
- Dopamine beta hydroxylase
- Phenylethanolamine N-methyltransferase
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| catabolism: |
- Catechol-O-methyl transferase
- Monoamine oxidase
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| glutamate→GABA |
| anabolism: |
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| catabolism: |
- 4-aminobutyrate transaminase
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| tryptophan→serotonin→melatonin |
- Tryptophan hydroxylase
- Aromatic L-amino acid decarboxylase
- Acetylserotonin O-methyltransferase
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| arginine→NO |
- Nitric oxide synthase (NOS1, NOS2, NOS3)
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| choline→Acetylcholine |
| anabolism: |
- Choline acetyltransferase
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| catabolism: |
- Cholinesterase (Acetylcholinesterase, Butyrylcholinesterase)
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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UpToDate Contents
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English Journal
- Serotonin suppresses food anticipatory activity and synchronizes the food-entrainable oscillator during time-restricted feeding.
- Rozenblit-Susan S1, Chapnik N1, Genzer Y1, Froy O2.
- Behavioural brain research.Behav Brain Res.2016 Jan 15;297:150-4. doi: 10.1016/j.bbr.2015.10.019. Epub 2015 Oct 20.
- The serotonergic and circadian systems are intertwined as serotonin modulates the response of the central brain suprachiasmatic nuclei (SCN) clock to light. Time-restricted feeding (RF) is characterized by increased food anticipatory activity (FAA) and controlled by the food-entrainable oscillator (
- PMID 26467604
- Dopamine induces an optimism bias in rats-Pharmacological proof for the translational validity of the ambiguous-cue interpretation test.
- Kregiel J1, Golebiowska J1, Popik P1, Rygula R2.
- Behavioural brain research.Behav Brain Res.2016 Jan 15;297:84-90. doi: 10.1016/j.bbr.2015.10.020. Epub 2015 Oct 14.
- Recent findings have revealed that pharmacological enhancement of dopaminergic (DA) function by the administration of a dopaminergic precursor (dihydroxy-l-phenylalanine; l-DOPA) increases an optimism bias in humans. This effect is due to l-DOPA's impairment of the ability to update beliefs in respo
- PMID 26462571
- Imaging genetics studies on monoaminergic genes in major depressive disorder.
- Won E1, Ham BJ2.
- Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2016 Jan 4;64:311-9. doi: 10.1016/j.pnpbp.2015.03.014. Epub 2015 Mar 27.
- Although depression is the leading cause of disability worldwide, current understanding of the neurobiology of depression has failed to be translated into clinical practice. Major depressive disorder (MDD) pathogenesis is considered to be significantly influenced by multiple risk genes, however gene
- PMID 25828849
Japanese Journal
- Effect of Selective Serotonin Reuptake Inhibitors via 5-HT_<1A> Receptors on L-DOPA-Induced Rotational Behavior in a Hemiparkinsonian Rat Model
- Inden Masatoshi,Abe Mari,Minamino Hideaki [他],TAKATA Kazuyuki,YOSHIMOTO Kanji,TOOYAMA Ikuo,KITAMURA Yoshihisa
- Journal of pharmacological sciences 119(1), 10-19, 2012-05-20
- … In this study, intranigral injection of 6-hydroxydopamine (6-OHDA) in rats caused a significant loss of tyrosine hydroxylase immunoreactivity in the striatum and substantia nigra. … However, tryptophan hydroxylase immunoreactivity of the striatum and raphe nucleus was unaffected by 6-OHDA. …
- NAID 10030760133
- NMDA Component of the Excitatory Synaptic Transmission of Neurons Containing Serotonin or GABA in the Ventrolateral Subdivision of the Periaqueductal Gray Matter of Mouse
- Shirakawa Kenshu
- Dokkyo journal of medical sciences 39(1), 17-27, 2012-03-25
- … We characterized the NMDA component of the excitatory synaptic transmission within the ventrolateral subdivision of the PAG( vlPAG) using a whole cell patch clamp technique and then detected the expression of tryptophan hydroxylase (TPH), serotonin synthesizing enzyme, and glutamate decarboxylase (GAD), GABA synthesizing enzyme to understand thevlPAG intrinsic neurotransmission. …
- NAID 110009005088
- Zincfingerhomeobox is required for the differentiation of serotonergicneurons in the seaurchinembryo
- Yaguchi Junko,Angerer Lynne M.,Inaba Kazuo,Yaguch Shunsuke,稲葉 一男,谷口 俊介
- Developmental biology 363(1), 74-83, 2012-03
- … Here, we report that zincfingerhomeobox (zfhx1/z81) is expressed in serotonergic neural precursor cells, using double in situ hybridization screening with a serotonergic neural marker, tryptophan 5-hydroxylase (tph) encoding a serotonin synthase that is required for the differentiation of serotonergicneurons. …
- NAID 120003988702
Related Links
- トリプトファンヒドロキシラーゼ（Tryptophan hydroxylase、TPH、EC 1.14.16.4）は、 神経伝達物質であるセロトニンを合成する酵素である。 ... BH4 Databases; ^ Three- Dimensional Structure of Human Tryptophan Hydroxylase and Its Implications for the ...
- The activity of tryptophan hydroxylase (i.e. the rate at which it converts L- tryptophan into the serotonin precursor L-5-hydroxytryptophan) can be increased when it undergoes phosphorylation. Protein Kinase A, for example, can phosphorylate ...
Related Pictures
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トリプトファン Trp W