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Crit Rev Clin Lab Sci. 1980;12(3):241-77.

Dopamine beta-hydroxylase in health and disease.

Abstract

DBH is a copper-containing oxygenase that catalyzes the hydroxylation of the beta carbon of a wide variety of phenylethylamine derivatives using molecular oxygen ascorbate as cofactors. It is a glycoprotein with a molecular weight of 290,000 and consists of four identical subunits, each with a single copper atom and 5% carbohydrate by weight. The enzyme is a constituent of catecholamine storage vesicles in chromaffin cell and adrenergic neurons in the peripheral and central nervous system where it functions to synthesize noradrenaline from dopamine. Although endogenous inhibitors have been isolated, they have not been demonstrated to have a physiological function, and the kinetics of the enzyme in vitro and in vivo suggest that the enzyme is not a rate limiting step in catecholamine synthesis under normal conditions. DBH exists in both a soluble form within vesicles and as a constituent of their membranes with its active site directed inward. The significance of the partition of the enzyme into soluble and membrane forms is not understood, although the soluble form has a fivefold greater homospecific activity. DBH has been one of the most intensively investigated enzymes in neurochemistry for several reasons. It is a readily assayable constitutent of catecholamine storage vesicles and, as such, provides a convenient biochemical marker for subcellular fractionation work and studies of the cellular regulation of catecholamine synthesis, storage, and release. The adrenal medulla is a rich source of the enzyme for purification, and the purified enzyme is highly antigenic, thereby enabling the use of several immunological techniques to study the cellular dynamics of the enzyme and the organelles in which it is located. These include radioimmunoassay, immunohistochemistry, and cytochemistry. This review firstly summarizes the present state of knowledge concerning the molecular properties of DBH. It then describes the tissue, cellular, and subcellular localization of the enzyme and its physiological regulation. The remainder of the review concentrates on those aspects of research on DBH in which the authors have participated that have led to general advances such as the development of the concept of homospecific activity, the introduction of immunohistochemistry for the localization of enzymes involved in transmitter metabolism, the release of macromolecules from synaptic vesicles during the process of exocytosis, the use of antibodies to DBH administered in vivo to study the fate of synaptic vesicle membranes and to produce specific immunological lesions of noradrenergic nerves in the peripheral and central nervous system, the genetic, environmental, and physiological determinants of serum DBH activity as an index of sympathetic function in animals and man, and the question of its diagnostic value in disease.

PMID:
6998654
DOI:
10.3109/10408368009108731
[Indexed for MEDLINE]

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