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6-Aminodopamine (6-NH2DA) and various analogs of 6-NH2DA have been evaluated for their ability to inactivate purified catechol O-methyltransferase (COMT) in vitro. The inactivation of COMT by these agents could be prevented by including an antioxidant in the preincubation mixture or by excluding oxygen; however, catalase did not protect the enzyme from inactivation. Substrate protection studies and kinetic studies suggested that the loss of enzyme activity resulted from the alkylation of an amino acid residue at the active site of COMT by the quinoid types products which were generated upon air oxidation of 6-NH2DA. In addition, we have explored in more detail the reactivity toward COMT of specific intermediates in the oxidation pathways of 6-NH2DA by using various 6-NH2DA analogs. From the above studies we have concluded that 6-aminodopamine-p-quinone (6-NH2DAQ) is perhaps the most toxic species toward COMT. However, the aminochromes which are formed from 6-NH2DAQ are also effective in inactivating COMT. The results of these studies have provided a useful model system for observing the interaction of 6-NH2DA and its oxidation products with proteins; in addition, it has provided additional insight into the topography of the active site of COMT.
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
March 1982,
Journal of medicinal chemistry,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
February 1975,
Journal of medicinal chemistry,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
October 1973,
Biochemical and biophysical research communications,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
January 1977,
Methods in enzymology,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
March 1975,
Biochemical and biophysical research communications,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
February 1983,
The Journal of biological chemistry,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
January 1981,
Methods in enzymology,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
January 1974,
International pharmacopsychiatry,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
September 1976,
Biochemical pharmacology,
R T Borchardt, and
E E Smissman, and
D Nerland, and
J R Reid
October 1976,
Journal of medicinal chemistry,
