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Dopamine beta-hydroxylase
Norepinephrine (NE) is a neurotransmitter with essential roles in both the central and peripheral nervous systems. Dopamine beta-hydroxylase (DβH, dopamine β-monooxygenase; EC 1.14.17.1) is an enzyme required to synthesize NE from dopamine (DA) in noradrenergic cells of the locus coeruleus (LC) and post ganglionic sympathetic fibers, as well as in adrenal medulla chromaffin cells and epinephrine neurons. NE interacts with three major types of receptors each with different subtypes α1-like (α1a, b, d), α2-like(α2a, b, c, d) and β-like (β1−3). Human DβH has four domains: one Dopamine Beta-Monooxygenase Nterminal (DOMON) domain, two copper catalytic cores, and a tetramerization domain. The DβH promoter contains numerous regulatory elements, with the most well-studied being a glucocorticoid transcription enhancer and a cyclic AMP (cAMP) response element (CRE) that overlaps an AP1 site in the gene promoter (at position - 184bp relative to the transcription start site).
Other regulators include SP1, Phox2a/Arix, Egr1, three homeodomains, AP2 and AP4. The three homeobox motifs can bind Phox2a/Arix, which is vital for cell-specific DβH gene expression. The overlapping CRE/AP1 motif can bind CREB and also AP1 family members. The transcription factor early growth response protein 1 (Egr1) also inhibits DβH expression. With such a complex regulatory promoter in the DβH gene, novel variants in the promoter region of the gene may have a dramatic and widespread effect on noradrenergic signaling.
References
1.Gonzalez-Lopez E,et al. J Neurochem. 2019 Oct 15.
Other regulators include SP1, Phox2a/Arix, Egr1, three homeodomains, AP2 and AP4. The three homeobox motifs can bind Phox2a/Arix, which is vital for cell-specific DβH gene expression. The overlapping CRE/AP1 motif can bind CREB and also AP1 family members. The transcription factor early growth response protein 1 (Egr1) also inhibits DβH expression. With such a complex regulatory promoter in the DβH gene, novel variants in the promoter region of the gene may have a dramatic and widespread effect on noradrenergic signaling.
References
1.Gonzalez-Lopez E,et al. J Neurochem. 2019 Oct 15.
Metabolic Enzyme/Protease
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