|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
|Dopamine beta-hydroxylase (dopamine beta-monooxygenase)|
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with reduced ascorbate as one donor, and incorporation of one ato of oxygen into the other donor. This enzyme participates in tyrosine metabolism. It has 3 cofactors: copper, PQQ, and Fumarate.
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.
Mechanism of catalysis
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.
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.
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.
DBH is in the catecholamine biosynthetic pathway. DBH has been shown to be associated with decision making and addictive behaviors such as alcohol and smoking, attention deficit hyperactivity disorder, and also with neurological diseases such as Schizophrenia and Alzheimer's. Inadequate DBH is called dopamine beta hydroxylase deficiency.
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.
The systematic name of this enzyme class is 3,4-dihydroxyphenethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating). Other names in common use include
- dopamine beta-hydroxylase,
- MDBH (membrane-associated dopamine beta-monooxygenase),
- SDBH (soluble dopamine beta-monooxygenase),
- oxygenase,dopamine beta-mono-,
- 3,4-dihydroxyphenethylamine beta-oxidase,
- 4-(2-aminoethyl)pyrocatechol beta-oxidase,
- dopa beta-hydroxylase,
- dopamine beta-oxidase,
- dopamine hydroxylase,
- phenylamine beta-hydroxylase, and
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- GeneReviews/NIH/NCBI/UW entry on Dopamine Beta-Hydroxylase Deficiency
- Dopamine beta-Hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH)