INHIBITION OF TYROSINE HYDROXYLASE, A Fe(II)-STIMULATED MONOOXYGENASE, BY BLEOMYCIN

Tyrosine hydroxylase was shown to be inhibited in vitro by bleomycin. At a concentration of 1×10-4 M, copper-free BLM-A2 inhibited tyrosine hydroxylase activity by 50%, and all other bleomycins investigated including copper-bound BLM-A2 showed similar degrees of inhibition of tyrosine hydroxylase. T...

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Bibliographic Details
Published in:Journal of antibiotics 1980, Vol.33(9), pp.1043-1047
Main Authors: OKA, KAZUHIRO, KATO, TAKESHI, TAKITA, TOMOHISA, TAKEUCH, TOMIO, UMEZAWA, HAMAO, NAGATSU, TOSHIHARU
Format: Article
Language:English
Subjects:
Adrenal Glands - enzymology
Animals
Bleomycin - pharmacology
Cattle
In Vitro Techniques
Iron - physiology
Kinetics
Structure-Activity Relationship
Tyrosine 3-Monooxygenase - antagonists & inhibitors
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Summary:Tyrosine hydroxylase was shown to be inhibited in vitro by bleomycin. At a concentration of 1×10-4 M, copper-free BLM-A2 inhibited tyrosine hydroxylase activity by 50%, and all other bleomycins investigated including copper-bound BLM-A2 showed similar degrees of inhibition of tyrosine hydroxylase. The kinetic data have shown that the inhibition by BLM-A2 is competitive with a tetrahydropterin cofactor (6-methyl-tetrahydropterin) and uncompetitive with tyrosine. The inhibition of tyrosine hydroxylase by bleomycin was not reversed by Fe(II) or superoxide dismutase. These results suggest that the inhibition may be neither due to the chelating action of bleomycin with ferrous ion nor due to the production of superoxide and hydroxyl radicals by the formation of an oxygen-labile Fe(II)-bleomycin complex.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.33.1043