View source for Dopamine beta-hydroxylase

{{Short description|Mammalian protein found in Homo sapiens}}
{{cs1 config|name-list-style=vanc}}
{{Infobox gene}}{{infobox enzyme
| Name       = dopamine beta-monooxygenase
| EC_number  = 1.14.17.1
| CAS_number = 9013-38-1
| GO_code    = 0004500
| image      =
| width      = 
| caption    = 
| align      = right 
}}'''Dopamine beta-hydroxylase''' ('''DBH'''), also known as '''dopamine beta-monooxygenase''', is an [[enzyme]] ({{EC number|1.14.17.1}}) that in humans is encoded by the DBH [[gene]]. Dopamine beta-hydroxylase [[catalysis|catalyzes]] the conversion of dopamine to norepinephrine.

[[File:Dopamine beta-monooxygenase reaction.svg|class=skin-invert-image|right|thumb|upright=2.2|Dopamine is converted to norepinephrine by the enzyme dopamine β-hydroxylase; ascorbic acid serves as a cofactor]]

The three [[substrate (biochemistry)|substrates]] of the enzyme are [[dopamine]], [[vitamin C]] (ascorbate), and [[oxygen|O<sub>2</sub>]]. The [[product (chemistry)|products]] are [[norepinephrine]], [[dehydroascorbate]], and [[water|H<sub>2</sub>O]].

DBH is a 290 kDa copper-containing [[oxygenase]] consisting of four identical subunits, and its activity requires [[ascorbate]] as a [[Cofactor (biochemistry)|cofactor]].<ref name="pmid6998654">{{cite journal | vauthors = Rush RA, Geffen LB | title = Dopamine beta-hydroxylase in health and disease | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 12 | issue = 3 | pages = 241–77 | year = 1980 | pmid = 6998654 | doi = 10.3109/10408368009108731 }}</ref>

It is the only enzyme involved in the synthesis of small-molecule neurotransmitters that is membrane-bound, making norepinephrine the only known transmitter synthesized inside vesicles.  It is expressed in noradrenergic neurons of the central nervous system (i.e. [[locus coeruleus]]) and peripheral nervous systems (i.e. sympathetic ganglia), as well as in [[chromaffin cell]]s of the [[adrenal medulla]].

== Mechanism of catalysis ==
Based on the observations of what happens when there is no substrate, or oxygen, the following steps seem to constitute the hydroxylation reaction.<ref name="S Kaufman, WF Bridgers, J Baron 1968 172–176">{{cite book| vauthors = Kaufman S, Bridgers WF, Baron J | title =  Oxidation of Organic Compounds| chapter = The Mechanism of Action of Dopamine β-Hydroxylase | series= Advances in Chemistry | volume =  77 | pages = 172–176  | year = 1968 | doi = 10.1021/ba-1968-0077.ch073 | isbn = 0-8412-0078-5 }}</ref><ref name="pmid4287853">{{cite journal | vauthors = Friedman S, Kaufman S | title = An electron paramagnetic resonance study of 3,4-dihydroxyphenylethylamine beta-hydroxylase | journal = The Journal of Biological Chemistry | volume = 241 | issue = 10 | pages = 2256–9 | date = May 1966 | doi = 10.1016/S0021-9258(18)96614-7 | pmid = 4287853 | doi-access = free }}</ref>

[[File:DBH mechanism.png|class=skin-invert-image|thumb|right|upright=1.2|In the absence of oxygen, dopamine or other substrates, the enzyme and ascorbate mixture produces reduced enzyme and dehydroascorbate. Exposing the reduced enzyme to oxygen and dopamine results in oxidation of the enzyme and formation of noradrenaline and water, and this step doesn't require ascorbate.]]

Although details of DBH mechanism are yet to be confirmed, DBH is homologous to another enzyme, peptidylglycine α-hydroxylating monooxygenase (PHM). Because DBH and PHM share similar structures, it is possible to model DBH mechanism based on what is known about PHM mechanism.<ref name="pmid11028916">{{cite journal | vauthors = Prigge ST, Mains RE, Eipper BA, Amzel LM | title = New insights into copper monooxygenases and peptide amidation: structure, mechanism and function | journal = Cellular and Molecular Life Sciences | volume = 57 | issue = 8–9 | pages = 1236–59 | date = August 2000 | pmid = 11028916 | doi = 10.1007/pl00000763 | s2cid = 12738480 | pmc = 11146793 }}</ref>

=== Substrate specificity ===
{{Catecholamine and trace amine biosynthesis|align=left}}
Dopamine beta-hydroxylase catalyzes the hydroxylation of not only dopamine but also other phenylethylamine derivatives when available. The minimum requirement seems to be the [[Phenethylamine|phenylethylamine]] skeleton: a benzene ring with a two-carbon side chain that terminates in an amino group.<ref name="S Kaufman, WF Bridgers, J Baron 1968 172–176"/>

== Assays for DBH activity in human serum and cerebrospinal fluid ==
DBH activity in human serum could be estimated by a [[spectrophotometric]] method <ref name="pmid5052101">{{cite journal | vauthors = Nagatsu T, Udenfriend S|title = Photometric Assay of Dopamine-β-Hydroxylase Activity in Human Blood|journal = Clinical Chemistry | volume = 18 | issue = 9 | pages = 980–983 | year = 1972 |doi = 10.1093/clinchem/18.9.980| pmid = 5052101 | doi-access = free }}</ref> or with the aid of Ultra high performance liquid chromatography with Photo Diode Array detector (UHPLC-PDA).<ref name="pmid30357655">{{cite journal | vauthors = Punchaichira TJ, Deshpande SN, Thelma BK|title = Determination of Dopamine-β-hydroxylase Activity in Human Serum Using UHPLC-PDA Detection|journal = Neurochemical Research  | volume = 43 | issue = 12 | pages = 2324–2332 | year = 2018 | pmid = 30357655 | doi = 10.1007/s11064-018-2653-1|s2cid = 53024826}}</ref> A sensitive assay for the detection of DBH activity in [[cerebrospinal fluid]] using [[High-performance liquid chromatography]] with Electrochemical detector(HPLC-ECD) was also described earlier.<ref name="pmid7264660">{{cite journal | vauthors = Matsui H, Kato T, Yamamoto C, Fujita K, Nagatsu T|title = Highly sensitive assay for dopamine-beta-hydroxylase activity in human cerebrospinal fluid by high performance liquid chromatography-electrochemical detection: properties of the enzyme|journal = Journal of Neurochemistry  | volume = 37 | issue = 2 | pages = 289–296 | year = 1981 | pmid = 7264660 | doi = 10.1111/j.1471-4159.1981.tb00454.x |s2cid = 42736106}}</ref>

=== Expression quantitative trait loci (eQTLs) at DBH loci ===
Genetic variants such as [[single-nucleotide polymorphisms]](SNPs)<ref name="pmid11170900">{{cite journal | vauthors =Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, Kim KS, Kim CH, Malison RT, Gelernter J, Cubells JF |title = A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus|journal = American Journal of Human Genetics  | volume = 68 | issue = 2 | pages = 515–22 | year = 2001 | pmid = 11170900 |pmc = 1235285| doi = 10.1086/318198 }}</ref><ref name="pmid26959714">{{cite journal | vauthors = Punchaichira TJ, Prasad S, Deshpande SN, Thelma BK |title = Deep sequencing identifies novel regulatory variants in the distal promoter region of the dopamine-beta-hydroxylase gene |journal = Pharmacogenetics and Genomics  | volume = 26 | issue = 7 | pages = 311–23 | year = 2016 | pmid = 26959714 | doi = 10.1097/FPC.0000000000000214|s2cid = 205601803 }}</ref> at DBH loci were found to be associated with DBH activity and are well known [[expression quantitative trait loci]]. [[Allele]] variants at two regulatory SNPs namely rs1611115 <ref name="pmid20009769">{{cite journal | vauthors = Chen Y, Wen G, Rao F, Zhang K, Wang L, Rodriguez-Flores JL, Sanchez, AP, Mahata M, Taupenot L, Sun P, Mahata SK, Tayo B, Schork NJ, Ziegler MG, Hamilton BA, O'Connor DT|title = Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure |journal = Journal of Hypertension  | volume = 28 | issue = 1 | pages = 76–86 | year = 2010 | pmid = 20009769 |pmc = 2860271 | doi = 10.1097/HJH.0b013e328332bc87 }}</ref> and rs1989787 <ref name="pmid20814407">{{cite journal | vauthors = Chen Y, Zhang K, Wen G, Rao F, Sanchez AP, Wang L, Rodriguez-Flores JL, Mahata M, Mahata SK, Waalen J, Ziegler MG, Hamilton BA, O'Connor DT |title = Human dopamine beta-hydroxylase promoter variant alters transcription in chromaffin cells, enzyme secretion, and blood pressure |journal = American Journal of Hypertension  | volume = 24 | issue = 1 | pages = 24–32 | year = 2011 | pmid = 20814407 |pmc = 4906639 | doi = 10.1038/ajh.2010.186 }}</ref> were shown to affect transcription of this gene. Mutations identified in [[dopamine beta hydroxylase deficiency]]<ref name="pmid21209083">{{cite journal | vauthors = Kim CH, Leung A, Huh YH, Yang E, Kim DJ, Leblanc P, Ryu H, Kim K, Kim DW, Garland EM, Raj SR, Biaggioni I, Robertson D, Kim KS|title = Norepinephrine deficiency is caused by combined abnormal mRNA processing and defective protein trafficking of dopamine beta-hydroxylase|journal = Journal of Biological Chemistry  | volume = 286 | issue = 11 | pages = 9196–204 | year = 2011 | pmid = 21209083 |pmc = 3059068| doi = 10.1074/jbc.M110.192351 |doi-access = free}}</ref> and non-synonymous SNPs such as rs6271 in this gene were found to cause defective secretion of the protein from  the endoplasmic reticulum.<ref name="pmid28707163">{{cite journal | vauthors = Punchaichira TJ, Dey SK, Mukhopadhyay A, Kundu S, Thelma BK|title = Characterization of SNPs in the dopamine-beta-hydroxylase gene providing new insights into its structure-function relationship |journal = Neurogenetics  | volume = 18 | issue = 3 | pages = 155–168 | year = 2017 | pmid = 28707163 | doi = 10.1007/s10048-017-0519-3 |s2cid = 5259134 }}</ref>

== Clinical significance ==
DBH primarily contributes to [[catecholamine]] and [[trace amine]] biosynthesis. It also participates in the metabolism of [[xenobiotic]]s related to these substances; for example, the human DBH enzyme catalyzes the beta-hydroxylation of [[amphetamine]] and [[para-hydroxyamphetamine]], producing [[norephedrine]] and [[para-hydroxynorephedrine]] respectively.<ref name="Substituted amphetamines, FMO, and DBH">{{cite book | author=Glennon RA | veditors=Lemke TL, Williams DA, Roche VF, Zito W | title=Foye's principles of medicinal chemistry | date=2013 | publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins | location=Philadelphia, US | isbn=9781609133450 | pages=646–648 | edition=7th | section-url=https://books.google.com/books?id=Sd6ot9ul-bUC&q=substituted%20derivatives%20substituents%20hydroxyamphetamine%20flavin%20monooxygenase&pg=PA646 | access-date=11 September 2015 | section=Phenylisopropylamine stimulants: amphetamine-related agents | quote=The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase.&nbsp;... Amphetamine can also undergo aromatic hydroxylation to ''p''-hydroxyamphetamine. &nbsp;... Subsequent oxidation at the benzylic position by DA β-hydroxylase affords ''p''-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine. | archive-date=8 March 2024 | archive-url=https://web.archive.org/web/20240308024354/https://books.google.com/books?id=Sd6ot9ul-bUC&q=substituted%20derivatives%20substituents%20hydroxyamphetamine%20flavin%20monooxygenase&pg=PA646#v=onepage&q=substituted%20derivatives%20substituents%20hydroxyamphetamine%20flavin%20monooxygenase&f=false | url-status=live }}</ref><ref name="DBH amph primary">{{cite journal | author = Taylor KB | title = Dopamine-beta-hydroxylase. Stereochemical course of the reaction | journal = J. Biol. Chem. | volume = 249 | issue = 2 | pages = 454–458 | date = January 1974 | doi = 10.1016/S0021-9258(19)43051-2 | pmid = 4809526 | access-date = 6 November 2014 | url = http://www.jbc.org/content/249/2/454.full.pdf | quote = Dopamine-β-hydroxylase catalyzed the removal of the pro-R hydrogen atom and the production of 1-norephedrine, (2S,1R)-2-amino-1-hydroxyl-1-phenylpropane, from d-amphetamine. | doi-access = free | archive-date = 7 October 2018 | archive-url = https://web.archive.org/web/20181007182156/http://www.jbc.org/content/249/2/454.full.pdf | url-status = live }}</ref><ref name="DBH 4-HA primary">{{cite journal | vauthors = Horwitz D, Alexander RW, Lovenberg W, Keiser HR | title = Human serum dopamine-β-hydroxylase. Relationship to hypertension and sympathetic activity | journal = Circ. Res. | volume = 32 | issue = 5 | pages = 594–599 | date = May 1973 | pmid = 4713201 | doi = 10.1161/01.RES.32.5.594 | quote =  Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine. | doi-access = free }}</ref>

DBH has been implicated as correlating factor in conditions associated with decision making and [[addictive drug]]s, e.g., alcoholism<ref>{{cite journal | vauthors = Mutschler J, Abbruzzese E, Witt SH, Dirican G, Nieratschker V, Frank J, Grosshans M, Rietschel M, Kiefer F | title = Functional polymorphism of the dopamine β-hydroxylase gene is associated with increased risk of disulfiram-induced adverse effects in alcohol-dependent patients | journal = Journal of Clinical Psychopharmacology | volume = 32 | issue = 4 | pages = 578–80 | date = August 2012 | pmid = 22760354 | doi = 10.1097/jcp.0b013e31825ddbe6 }}</ref> and smoking,<ref>{{cite journal | vauthors = Ella E, Sato N, Nishizawa D, Kageyama S, Yamada H, Kurabe N, Ishino K, Tao H, Tanioka F, Nozawa A, Renyin C, Shinmura K, Ikeda K, Sugimura H | title = Association between dopamine beta hydroxylase rs5320 polymorphism and smoking behaviour in elderly Japanese | journal = Journal of Human Genetics | volume = 57 | issue = 6 | pages = 385–90 | date = June 2012 | pmid = 22513716 | doi = 10.1038/jhg.2012.40 | doi-access = free }}</ref> [[attention deficit hyperactivity disorder]],<ref name="pmid15767706">{{cite journal | vauthors = Bhaduri N, Sinha S, Chattopadhyay A, Gangopadhyay PK, Singh M, Mukhopadhyay KK | title = Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children | journal = Indian Pediatrics | volume = 42 | issue = 2 | pages = 123–9 | date = February 2005 | pmid = 15767706 }}</ref> [[schizophrenia]],<ref>{{cite journal | vauthors = Cubells JF, Sun X, Li W, Bonsall RW, McGrath JA, Avramopoulos D, Lasseter VK, Wolyniec PS, Tang YL, Mercer K, Pulver AE, Elston RC | title = Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia | journal = Human Genetics | volume = 130 | issue = 5 | pages = 635–43 | date = November 2011 | pmid = 21509519 | doi = 10.1007/s00439-011-0989-6 | pmc=3193571}}</ref> and [[Alzheimer's disease]].<ref>{{cite journal | vauthors = Combarros O, Warden DR, Hammond N, Cortina-Borja M, Belbin O, Lehmann MG, Wilcock GK, Brown K, Kehoe PG, Barber R, Coto E, Alvarez V, Deloukas P, Gwilliam R, Heun R, Kölsch H, Mateo I, Oulhaj A, Arias-Vásquez A, Schuur M, Aulchenko YS, Ikram MA, Breteler MM, van Duijn CM, Morgan K, Smith AD, Lehmann DJ | title = The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project | journal = BMC Medical Genetics | volume = 11 | issue = 161 | pages = 162 | year = 2010 | pmid = 21070631 | doi = 10.1186/1471-2350-11-162 | pmc=2994840 | doi-access = free }}</ref> Inadequate DBH is called [[dopamine beta hydroxylase deficiency]].

The proximal [[Promoter (genetics)|promoter]] SNPs rs1989787  and rs1611115 were found to be associated with cognition in [[schizophrenia]] subjects.<ref name="pmid31913053">{{cite journal | vauthors = Punchaichira TJ, Mukhopadhyay A, Kukshal P, Bhatia T, Deshpande SN, Thelma BK | title = Association of regulatory variants of dopamine β-hydroxylase with cognition and tardive dyskinesia in schizophrenia subjects | journal = Journal of Psychopharmacology | pages = 358–369 | year = 2020 | volume = 34 | issue = 3 | pmid =31913053 | doi = 10.1177/0269881119895539 | pmc = 7150076 }}</ref> Further these SNPs (rs1989787;rs1611115) and  a distal promoter variant 19bp Ins/Del(rs141116007) were associated with scores of Abnormal Involuntary Movement Scale in [[tardive dyskinesia]] positive  schizophrenia subjects.<ref name="pmid31913053"/> Of the three variants, the proximal promoter SNP(rs1611115) was associated with  [[Positive and Negative Syndrome Scale]](PANSS) scores in [[tardive dyskinesia]] positive  schizophrenia subjects.<ref name="pmid31913053"/> The main effect of a putative splice variant in Dopamine beta-hydroxylase namely rs1108580 was found to be associated with Working memory <sub>Processing speed</sub> in a north Indian [[Schizophrenia]] case control study where the G/G genotype of that [[single-nucleotide polymorphism]](SNP) was found to have lower cognitive scores than those with A/A and A/G genotypes. Furthermore the same SNP was associated with Emotion <sub>accuracy</sub> in healthy controls.<ref name="pmid37493923">{{cite journal | vauthors = Punchaichira TJ, Kukshal P, Bhatia T, Deshpande SN|title = Effect of rs1108580 of DBH and rs1006737 of CACNA1C on Cognition and Tardive Dyskinesia in a North Indian Schizophrenia Cohort|journal = Molecular Neurobiology | year = 2023 | volume=60 | issue=12 | pages=6826–6839 | pmid = 37493923 | doi = 10.1007/s12035-023-03496-4 | s2cid=260162784 }}</ref>
{{clear}}

== Structure ==
[[File:Models for Oligomer Structures of DBH.png|thumb|right|upright=1.2|Experimental DBH structural model based upon [[In silico medicine|in silico prediction]] and physiochemical validation<ref name="pmid22028891">{{cite journal | vauthors = Kapoor A, Shandilya M, Kundu S | title = Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms | journal = PLOS ONE | volume = 6 | issue = 10 | pages = e26509 | year = 2011 | pmid = 22028891 | pmc = 3197665 | doi = 10.1371/journal.pone.0026509 | bibcode = 2011PLoSO...626509K | doi-access = free }}</ref>]]
It was difficult to obtain a stable crystal of dopamine beta-hydroxylase. Hence an homology model based on the primary sequence and comparison to PHM is available.<ref name="pmid22028891"/>

However, a crystal structure was also put forward in 2016.<ref name="pmid27152332">{{cite journal | vauthors = Vendelboe TV, Harris P, Zhao Y, Walter TS, Harlos K, Omari KE, Christensen HM|title = The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution|journal =  Science Advances| volume = 2 | issue = 4|pages = e1500980| year = 2016 | pmid = 27152332 |pmc = 4846438| doi = 10.1126/sciadv.1500980 |bibcode = 2016SciA....2E0980V}}</ref>
{{clear}}

== Regulation and inhibition ==
This protein may use the [[morpheein]] model of [[allosteric regulation]].<ref name="pmid22182754">{{cite journal | vauthors = Selwood T, Jaffe EK | title = Dynamic dissociating homo-oligomers and the control of protein function | journal = Archives of Biochemistry and Biophysics | volume = 519 | issue = 2 | pages = 131–43 | date = March 2012 | pmid = 22182754 | pmc = 3298769 | doi = 10.1016/j.abb.2011.11.020 }}</ref>

=== Inhibitors ===
{| class="wikitable"
|+Types of dopamine beta-hydroxylase inhibition{{Clarify|reason=Unclear what this chart is describing, and the role/purpose of ascorbate/tyramine in the chart. Does it mean that hydralazine binds to both the ascorbate cofactor site as well as the tyramine active site?|date=January 2020}}{{Citation needed|date=January 2020}}
!
!HYD{{efn|hydralazine}}
!HP{{efn|2-hydrazinopyridine}}
!QCA{{efn|2-quinoline-carboxylic acid}}
!IQCA{{efn|l-isoquinolinecarboxylic acid}}
!BI{{efn|2,2'-biimidazole}}
!IAA{{efn|imidazole-4-acetic acid}}[https://pubchem.ncbi.nlm.nih.gov/compound/Imidazoleacetic-acid]
|-
![[Competitive inhibition|Competitive]]
|Ascorbate
|Ascorbate
|Ascorbate
|Ascorbate
|Ascorbate
|Ascorbate
|-
![[Uncompetitive inhibition|Uncompetitive]]
|
|
|Tyramine
|Tyramine
|
|
|-
!Mixed
|Tyramine
|Tyramine
|
|
|Tyramine
|Tyramine
|-
|colspan=7 |Ascorbate is cofactor; tyramine is substitute for dopamine, DBH's namesake substrate
{{notelist|20em}}
|}

DBH is inhibited by [[disulfiram]],<ref>{{cite journal | vauthors = Goldstein M, Anagnoste B, Lauber E, Mckeregham MR | journal = Life Sciences | volume = 3 | issue = 7 | pages = 763–7 | date = July 1964 | pmid = 14203977 | doi = 10.1016/0024-3205(64)90031-1 | title = Inhibition of dopamine- β -hydroxylase by disulfiram }}</ref> [[tropolone]],<ref>{{cite journal | vauthors = Goldstein M, Lauber E, Mckereghan MR | journal = Biochemical Pharmacology | volume = 13 | issue = 7 | pages = 1103–6 | date = July 1964 | pmid = 14201135 | doi = 10.1016/0006-2952(64)90109-1 | title = The inhibitionof dopamine-β-hydroxylase by tropolone and other chelating agents }}</ref> and, most selectively, by [[nepicastat]].<ref>{{cite journal | vauthors = Stanley WC, Li B, Bonhaus DW, Johnson LG, Lee K, Porter S, Walker K, Martinez G, Eglen RM, Whiting RL, Hegde SS | title = Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase | journal = British Journal of Pharmacology | volume = 121 | issue = 8 | pages = 1803–9 | date = August 1997 | pmid = 9283721 | pmc = 1564872 | doi = 10.1038/sj.bjp.0701315 }}</ref> It is also inhibited by [[etamicastat]] and [[zamicastat]].<ref name="DeySainiPrabhakar2020">{{cite journal | vauthors = Dey SK, Saini M, Prabhakar P, Kundu S | title = Dopamine β hydroxylase as a potential drug target to combat hypertension | journal = Expert Opin Investig Drugs | volume = 29 | issue = 9 | pages = 1043–1057 | date = September 2020 | pmid = 32658551 | doi = 10.1080/13543784.2020.1795830 | url = }}</ref>

DBH is reversibly inhibited by l-2H-Phthalazine hydrazone (hydralazine; HYD), 2-1H-pyridinone hydrazone (2-hydrazinopyridine; HP), 2-quinoline-carboxylic acid (QCA), l-isoquinolinecarboxylic acid (IQCA), 2,2'-bi-lH-imidazole (2,2'-biimidazole; BI), and IH-imidazole-4-acetic acid (imidazole-4-acetic acid;[https://pubchem.ncbi.nlm.nih.gov/compound/Imidazoleacetic-acid] IAA). HYD, QCA, and IAA are allosteric competitive.<ref name="pmid2306475">{{cite journal | vauthors = Townes S, Titone C, Rosenberg RC | title = Inhibition of dopamine beta-hydroxylase by bidentate chelating agents | journal = Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology | volume = 1037 | issue = 2 | pages = 240–7 | date = February 1990 | pmid = 2306475 | doi = 10.1016/0167-4838(90)90174-E }}</ref>

== Nomenclature ==
The [[List of enzymes|systematic name]] of this enzyme class is ''3,4-dihydroxyphenethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating)''.

Other names in common use include:

* dopamine beta-monooxygenase
* dopamine beta-hydroxylase
* membrane-associated dopamine beta-monooxygenase (MDBH)
* soluble dopamine beta-monooxygenase (SDBH)
* dopamine-B-hydroxylase
* 3,4-dihydroxyphenethylamine beta-oxidase
* 4-(2-aminoethyl) pyrocatechol beta-oxidase
* dopa beta-hydroxylase
* dopamine beta-oxidase
* dopamine hydroxylase
* phenylamine beta-hydroxylase
* (3,4-dihydroxyphenethylamine) beta-mono-oxygenase

== References ==
{{reflist|35em}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Friedman S, Kaufman S | title = 3,4-dihydroxyphenylethylamine beta-hydroxylase. Physical properties, copper content, and role of copper in the catalytic activity | journal = The Journal of Biological Chemistry | volume = 240 | issue = 12 | pages = 4763–73 | date = December 1965 | doi = 10.1016/S0021-9258(18)97021-3 | pmid = 5846992 | doi-access = free }}
* {{cite journal | vauthors = Levin EY, Levenberg B, Kaufman S | year = 1960 | title = The enzymatic conversion of 3,4-dihydroxyphenylethylamine to norepinephrine | journal = J. Biol. Chem.  | volume = 235 | issue = 7 | pages = 2080&ndash;2086 | doi = 10.1016/S0021-9258(18)69366-4 | pmid = 14416204 | doi-access = free }}
{{refend}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=dbh  GeneReviews/NIH/NCBI/UW entry on Dopamine Beta-Hydroxylase Deficiency]
* {{MeshName|Dopamine+beta-Hydroxylase}}

{{Neurotransmitter metabolism enzymes}}
{{Dioxygenases}}
{{Enzymes}}
{{Monoamine metabolism modulators}}
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{{Use dmy dates|date=April 2017}}

[[Category:EC 1.14.17]]
[[Category:Copper enzymes]]
[[Category:Enzymes of known structure]]
[[Category:Biology of attention deficit hyperactivity disorder]]
[[Category:Amphetamine]]