Dopamine-B-hydroxylase

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

Figure 1. Biosynthetic pathways for biogenic amines. In Drosophila and vertebrates decarboxylation of DOPA and 5-hydroxy-tryptophan is catalyzed by the same enzyme, DDC. In vertebrates this enzyme is called amino acid decarboxylase (AADC). Only vertebrates further metabolize dopamine to norepinephrine and epinephrine. TH, tryosine hydroxylase DDC, DOPA decarboxylase DBH, dopamine b-hydroxylase PNMT, phenylethanolamine N-methyltransferase. Tryp-OH tryptophan hydroxylase.

Murphy DL, Donnelly C, Moskowitz J Inhibition by lithium of prostaglandin El and norepinephrine effects on cyclic adenosine monophosphate production in human platelets. Chn Pharmacol Ther 14 810-814, 1974b Murphy DL, Lake CR, et al Psychoactive drug effects on plasma norepinephrine and plasma dopamine B-hydroxylase in man, in Catecholamines Basic and Clinical Frontiers. Edited by Usdin E, Kopin IJ, Barchas J. Ehnsford, NY, Pergamon, 1979, pp 918-920... 

In an effort to find a biological process that may identify a specific genotype, differences in various enzymes (e.g., monoamine oxidase, dopamine b-hydroxylase, and catechol-O-methyltransferase) have also been investigated. 

Schematic diagram of a generalized noradrenergic junction (not to scale). Tyrosine is transported into the noradrenergic ending or varicosity by a sodium-dependent carrier (A). Tyrosine is converted to dopamine (see Figure 6-5 for details), which is transported into the vesicle by a carrier (B) that can be blocked by reserpine. The same carrier transports norepinephrine (NE) and several other amines into these granules. Dopamine is converted to NE in the vesicle by dopamine-B-hydroxylase. Release of transmitter occurs when an action potential opens voltage-sensitive calcium channels and increases intracellular calcium. Fusion of vesicles with the surface membrane results in expulsion of norepinephrine, cotransmitters, and dopamine-13-hydroxylase.

Fig. 27. Modulatory transmitter systems in piriform cortex. Darkfield photomicrographs showing the distribution of dopaminergic (A), noradrenergic (B) and serotonergic (C) fibers in piriform cortex The axons are shown using antibodies to tyrosine hydroxylase (TH), dopamine-B-hydroxylase (DBH) and serotonin (5-HT) and immunocytochemistry. Dorsal is at the top and midline is to the left in all micrographs.

Figure 9-1. Biosynthesis of catecholamines. Denotes enzyme in transformation AADC = aromatic L-amino acid decarboxylase COMT = catechol-o-methyl transferase DBH = dopamine-B-hydroxylase MAO = monoamine oxidase PNMT = phenylethanolamine-N-methyl transferase TH = tyrosine hydroxylase.

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