World Library  
Flag as Inappropriate
Email this Article

Dopamine-beta-hydroxylase

Article Id: WHEBN0011042421
Reproduction Date:

Title: Dopamine-beta-hydroxylase  
Author: World Heritage Encyclopedia
Language: English
Subject: Attention deficit hyperactivity disorder, DBH
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Dopamine-beta-hydroxylase

Dopamine beta-hydroxylase (dopamine beta-monooxygenase)
Identifiers
1.14.17.1
RNA expression pattern

Dopamine β-hydroxylase (DBH) is an enzyme that converts dopamine to norepinephrine.

DBH is a 290 kDa copper-containing oxygenase consisting of four identical subunits, and its activity requires ascorbate as a cofactor.[1] It is the only enzyme involved in the synthesis of small-molecule neurotransmitters that is membrane-bound, making norepinephrine the only transmitter synthesized inside vesicles. It is expressed in noradrenergic nerve terminals of the central and peripheral nervous systems, as well as in chromaffin cells of the adrenal medulla.

DBH is inhibited by disulfiram,[2] tropolone,[3] and, most selectively, by nepicastat.[4]

Mechanism

Based on the observations of what happens when there's no substrate, or oxygen, the following steps seem to constitute the hydroxylation reaction.[5][6]

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.[7]

Substrate Specificity

Dopamine beta-hydroxylase catalyzes the hydroxylation of not only dopamine but also other phenylethylamine derivatives when available. The minimum requirement seems to be a benzene ring with a two-carbon side chain that terminates in an amino group.[8]

Structure

Because it is difficult to obtain a stable crystal of dopamine beta-hydroxylase, its crystal structure is yet to be discovered. However, a model based on the primary sequence and comparison to PHM is available.[9]

Biological Functions

DBH is in the catecholamine biosynthetic pathway. DBH has been shown to be associated with decision making and addictive behaviors such as alcohol[10] and smoking,[11] attention deficit hyperactivity disorder,[12] and also with neurological diseases such as Schizophrenia[13] and Alzheimer's.[14]

Regulation

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; IAA). HYD, QCA, and IAA are allosteric competitive [15]

See also

References

External links

  • GeneReviews/NIH/NCBI/UW entry on Dopamine Beta-Hydroxylase Deficiency
  • Medical Subject Headings (MeSH)
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.