Dopamine- S-hydroxylase

It is possible to deplete the brain of both DA and NA by inhibiting tyrosine hydroxylase but while NA may be reduced independently by inhibiting dopamine jS-hydroxylase, the enzyme that converts DA to NA, there is no way of specifically losing DA other than by destruction of its neurons (see below). In contrast, it is easier to augment DA than NA by giving the precursor dopa because of its rapid conversion to DA and the limit imposed on its further synthesis to NA by the restriction of dopamine S-hydroxylase to the vesicles of NA terminals. The activity of the rate-limiting enzyme tyrosine hydroxylase is controlled by the cytoplasmic concentration of DA (normal end-product inhibition), presynaptic dopamine autoreceptors (in addition to their effect on release) and impulse flow, which appears to increase the affinity of tyrosine hydroxylase for its tetrahydropteridine co-factor (see below). 

Dopamine /S-hydroxylase adsorbed on gold electrode has been investigated elec-trochemically and applying quartz crystal microbalance [198]. In the neutral phosphate buffer solution, the adsorbed layer was stable and did not desorb within the potential range of 0.6 to —0.7 V (versus AglAgCl —1 M KCl). At potentials more positive than 0.8 V, the adsorbed compound was oxidized and, probably, residual tyrosine, tryptophan, and histidine participated in this process. 

Reactions 2, 3, and 4 tell us little about how oxygen is activated during the hydroxylation reaction, and at the moment one can only speculate about the details. The scheme and the results on which it is based do, however, rule out several general types of hydroxylation mechanism. The fact that the enzyme can be reduced anaerobically by ascorbate to a form which actively supports substrate hydroxylation in the absence of ascorbate rules out any mechanism for this enzyme-catalyzed reaction in which the ascorbate functions as an oxygen carrier. Such a role has been postulated for tetrahydropteridines (id), which can serve as specific electron-donating cofactors (just as ascorbate does with dopamine )S-hydroxylase) in certain aromatic hydroxylation reactions (iO, 12). 

CioHijNOj, Mr 179.22, mp. 108-109 °C, crystals. F. is produced by various Fusarium species and is one of the toxins responsible for wilting [see wilting (withering) agents]. F. has herbicidal, insecticidal, and antibacterial activities, it lowers blood pressure, inhibits dopamine [S-hydroxylase, and has emetic effects in dogs (on oral administration from 10 mg/kg). The LDjq for mice is about 2 mg/animal (i. p.). 

Hirschsprung s disease have ETB receptor mutations). The lack of ET-3/ETB receptor results in the absence of parasympathic ganglionic neurons in the myenteric plexus (Auerbach). Mice with an ET-3/ETB receptor disruption die within 2 weeks after birth. In transgenic mice, in which the expression of the ETB receptor is driven by the dopamine (3-hydroxylase promoter, normal myenteric plexus are present and no enteric disorder develops. These mice, however, show a salt-sensitive hypertension, which can be efficiently treated with amiloride, indicating that ETB receptors are involved in the regulation of natriuresis via the amilorid-sensitive sodium channel ENaC. 

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. 

Zabetian, C.P., Anderson, G.M., Buxbaum, S.G., Elston, R.C., Ichi-nose, H., Nagatsu, T., Kim, K.S., Kim, C.H., Malison, R.T., Gel-ernter, J., and Cubells, J.E (2001) A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 68 515-522. 

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. 

Diliberto. E. J., Jr., Kaufman, S. Lack of inhibition of dopamine-p-hydroxylase by superoxide dismutase. In Superoxide and Superoxide Dismutases (Michelson, A. M., McCord, J. M Fridovich, I., eds.), London-New York-San Francisco, Academic Press, 1977, pp. 407-408... 

Aquayamycin. A strong inhibitor of tyrosine hydroxylase and dopamine /1-hydroxylase isolated from S. misawanesis contains a hydroxylated dihydro-pyran C-glycoside substituted at C-9 [150-152]. 

Tyrosine is converted to dopa by the rate-limiting enzyme tyrosine hydroxylase, which requires tetrahydrobiopterin, and is inhibited by a-methyltyrosine. Dopa is decarboxylated to dopamine by L-aromatic amino acid decarboxylase, which requires pyridoxal phosphate (vitamin B6) as a coenzyme. Carbidopa, which is used with levodopa in the treatment of parkinsonism, inhibits this enzyme. Dopamine is converted to norepinephrine by dopamine P-hydroxylase, which requires ascorbic acid (vitamin C), and is inhibited by diethyldithiocarbamate. Norepinephrine is converted to epinephrine by phenylethanolamine A -methyltransferase (PNMT), requiring S-adeno-sylmethionine. The activity of PNMT is stimulated by corticosteroids. 

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. 

Diabetic autonomic neuropathy Parkinson s disease Hyperthyroidism Multiple system atrophy Quadriplegia Amyloidosis Pure autonomic failure Familial dysautonomia Dopamine P-hydroxylase deficiency... 

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

Xie X, Xu L, Liu H, Chen W, Zhuang D, Zhang J, Duan S, Zhou W (2013) Positive association between -1021TT genotype of dopamine beta hydroxylase gene and progressive behavior of injection heroin users. Neurosci Lett 541 258-262... 

Schank JR, Ventura R, Puglisi-Allegra S, Alcaro A, Cole CD, Files LC, Seeman P, Weinshenker D (2006) Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine. Neuropsychopharmacology 31 2221-2230... 

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