Dopamine beta-hydroxylase

Bourdelat-Parks B., Anderson G., Donaldson Z. et al. (2005). Effects of dopamine beta-hydroxylase genotype and disulfiram inhibition on catecholamine homeostasis in mice. Psychopharmacol. (Berl). 183, 72-80. 

Baldo B. A., Daniel R. A., Berridge C. W., Kelley A. E. (2003). Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J. Comp. Neurol. 464, 220-37. 

Craine, J. E., Daniels, G. H. and Kaufman, S. Dopamine-beta-hydroxylase. The subunit structure and anion activation of the bovine adrenal enzyme. /. Biol. Chem. 248 7838-7844, 1973. 

Lamouroux, A., Vigny, A., Faucon Biguet, N. etal. The primary structure of human dopamine-beta-hydroxylase insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO J. 6 3931-3937,1987. 

Copper is part of several essential enzymes including tyrosinase (melanin production), dopamine beta-hydroxylase (catecholamine production), copper-zinc superoxide dismutase (free radical detoxification), and cytochrome oxidase and ceruloplasmin (iron conversion) (Aaseth and Norseth 1986). All terrestrial animals contain copper as a constituent of cytochrome c oxidase, monophenol oxidase, plasma monoamine oxidase, and copper protein complexes (Schroeder et al. 1966). Excess copper causes a variety of toxic effects, including altered permeability of cellular membranes. The primary target for free cupric ions in the cellular membranes are thiol groups that reduce cupric (Cu+2) to cuprous (Cu+1) upon simultaneous oxidation to disulfides in the membrane. Cuprous ions are reoxidized to Cu+2 in the presence of molecular oxygen molecular oxygen is thereby converted to the toxic superoxide radical O2, which induces lipoperoxidation (Aaseth and Norseth 1986). 

Cubells, J.F., Kranzler, H.R., McCance-Katz, E., Anderson, G.M., Malison, R.T., Price, L.H., and Gelernter, J. (2000) A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5 56-63. 

The dopamine beta-hydroxylase (Dbh) gene is necessary for the production of NE and epinephrine. Disruption of this gene results in the absence of NE and epinephrine production and is therefore used in studies determining the roles of these neurotransmitters. This approach is favored over the knockout of adrenergic receptors because of the multiplicity of receptor types for NE and epinephrine. 

Thomas, S.A., Palmiter, R.D. (1997) Disruption of the dopamine beta-hydroxylase gene in mice suggests roles for neuropinephrine in motor function, learning memory. Behav Neurosci 1110 579-89. 

Major LF, Lerner P, Ballenge JC, et al. Dopamine beta-hydroxylase in the cerebrospinal fluid relationship to disulfiram-induced psychosis. Bioi Psychiatry 1979 14 337-344. 

Noradrenergic neurons. The noradrenergic neuron uses NE for its neurotransmitter. Monoamine neurotransmitters are synthesized by means of enzymes, which assemble neurotransmitters in the cell body or nerve terminal. For the noradrenergic neuron, this process starts with tyrosine, the amino acid precursor of NE, which is transported into the nervous system from the blood by means of an active transport pump (Fig. 5 — 17). Once inside the neuron, the tyrosine is acted on by three enzymes in sequence, the first of which is tyrosine hydroxylase (TOH), the rate-limiting and most important enzyme in the regulation of NE synthesis. Tyrosine hydroxylase converts the amino acid tyrosine into dihydroxyphenylalanine (DOPA). The second enzyme DOPA decarboxylase (DDC), then acts, converting DOPA into dopamine (DA), which itself is a neurotransmitter in some neurons. However, for NE neurons, DA is just a precursor of NE. In fact, the third and final NE synthetic enzyme, dopamine beta-hydroxylase (DBH), converts DA into NE. The NE is then stored in synaptic packages called vesicles until released by a nerve impulse (Fig. 5—17). 

Dopaminergic neurons. Dopaminergic neurons utilize the neutotransmitter DA, which is synthesized in dopaminergic nerve terminals by two out of three of the same enzymes that also synthesize NE (Fig. 5—31). However, DA neurons lack the third enzyme, namely, dopamine beta hydroxylase, and thus cannot convert DA to NE. Therefore, it is DA that is stored and used for neurotransmitting purposes. 

Iversen LL, Rossor MN, Reynolds GP, Hills R, Roth M, Mountjoy CQ, Foote SL, Morrison JH, Bloom FE (1983) Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer s type. Neurosci. Lett. 39 95-100. 

Campbell MJ, Lewis DA, Foote SL, Morrison JH (1987) Distribution of choline acetyltransferase-, serotonin-, dopamine-beta-hydroxylase-, tyrosine hydroxylase-immunoreactive fibers in monkey primary auditory cortex. J Comp Neurol 267 209-220. 

Gaspar P, Berger B, Febvret A, Vigny A, Henry JP (1989) Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-beta-hydroxylase. J Comp Neurol 279 249-271. 

Ewing JA, Rouse BA, Mueller RA, Silver D. Can dopamine beta-hydroxylase levels predict adverse reactions to disulfiram Alcohol Clin Exp Res 1978 2(l) 93-4. 

Dopamine beta-hydroxylase Adrenal glands Conversion of dopamine to norepinephrine... 

Biaggioni I, Goldstein DS, Atkinson T, Robertson D. Dopamine-beta-hydroxylase deficiency in humans. Neurology 1990 40 370-3. 

Kaler SG, Holmes CS, Goldstein DS. Dopamine beta-hydroxylase deficiency associated with mutations in a copper transporter gene. Adv Pharmacol 1998 42 66-8. 

Kosten TR, Wu G, Huang W, Harding MJ, Hamon SC, Lappalainen J, Nielsen DA (2013) Pharmacogenetic randomized trial for cocaine abuse disulftram and dopamine beta-hydroxylase. Biol Psychiatry 73 219-224... 

Kaufman S, Friedman S (1965) Dopamine-beta-hydroxylase. Pharmacol Rev 17 71-100... 

Weinshilboum RM (1978) Serum dopamine beta-hydroxylase. Pharmacol Rev 30 133-166... 

Stewart LC, Klinman JP (1988) Dopamine beta-hydroxylase of adrenal chromaffin granules structure and function. Annu Rev Biochem 57 551-592... 

Weinshilboum RM, Raymond FA, Elveback LR, Weidman WH (1973) Serum dopamine-beta-hydroxylase activity sibling-sibling correlation. Science 181 943-945... 

Wei J, Ramchand CN, Hemmings GP (1997) Possible control of dopamine beta-hydroxylase via a codominant mechanism associated with the polymorphic (GT)n repeat at its gene locus in healthy individuals. Hum Genet 99 52-55... 

Wei J, Xu HM, Ramchand CN, Hemmings GP (1997) Is the polymorphic microsatellite repeat of the dopamine beta-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia Biol Psychiatry 41 762-767... 

Cubells JF, van Kammen DP, Kelley ME, Anderson GM, O Connor DT, Price LH, Malison R, Rao PA, Kobayashi K, Nagatsu T, Gelernter J (1998) Dopamine beta-hydroxylase two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet 102 533-540... 

Zabetian CP, Buxbaum SG, Elston RC, Kohnke MD, Anderson GM, Gelernter J, Cubells JF (2003) The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Am J Hum Genet 72 1389-1400... 

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