Dopamine-β-hydroxylase

Dopamine-β-hydroxylase
Identifiers
EC number	1.14.17.1
CAS number	9032-23-1
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 / QuickGO
Search PMC articles PubMed articles NCBI proteins

Dopamine-β-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme that catalyzes the conversion of dopamine into norepinephrine, an essential reaction in the biosynthesis of catecholamines. This enzyme is found primarily in the synaptic vesicles of neurons in the adrenal medulla and the nervous system.

Function

Dopamine-β-hydroxylase is responsible for the hydroxylation of dopamine, a key step in the catecholamine biosynthesis pathway. The reaction catalyzed by DBH involves the conversion of dopamine to norepinephrine by adding a hydroxyl group to the beta position of the benzene ring of dopamine. This reaction is critical for the production of norepinephrine, which serves as a neurotransmitter and a hormone, playing a significant role in the body's response to stress.

Structure

Dopamine-β-hydroxylase is a copper-containing oxidoreductase that binds to copper ions and uses ascorbic acid as a cofactor. The enzyme is a tetramer composed of four identical subunits, each containing a copper ion necessary for its catalytic activity.

Genetic Regulation

The gene encoding dopamine-β-hydroxylase is located on chromosome 9 in humans. Variations in this gene have been associated with differences in enzyme activity and norepinephrine levels, which can affect susceptibility to psychiatric disorders such as schizophrenia and depression.

Clinical Significance

Abnormal levels of dopamine-β-hydroxylase can lead to disorders in catecholamine metabolism, impacting both neurological and cardiovascular systems. Deficiencies in DBH activity can result in conditions such as Dopamine beta-hydroxylase deficiency, a rare disorder characterized by severe orthostatic hypotension. Additionally, variations in DBH expression and activity have been implicated in the development of certain psychiatric and behavioral disorders.

Research

Research on dopamine-β-hydroxylase includes studies aimed at understanding its role in neurotransmitter regulation and its potential as a target for therapeutic drugs. Inhibitors of DBH, such as disulfiram, are explored for their potential to modulate catecholamine levels in diseases like hypertension and certain types of addiction.

See Also

• Catecholamine biosynthesis
• Neurotransmitter
• Enzyme inhibitor