Inactivation of ornithine decarboxylase by intermediates of tyrosinase-catalyzed reaction.
1. Intermediates in the process of melanin synthesis formed through oxidation of catechols by tyrosinase produced the inactivation of ornithine decarboxylase (ODC), a key enzyme in the polyamine biosynthesis pathway. 2. The inactivation was dependent on the substrate used (dihydroxybenzylamine > L-3,4-dihydroxyphenylalanine > L-tyrosine) and on the concentration of intermediate produced rather than on the rate of formation. 3. Sulfhydryl compounds (dithiothreitol and glutathione) or quinone-reducing agents (ascorbic acid) prevented the inactivation of ODC; L-ornithine, but not other amino acids, also protected partially ODC. The results suggest that different cysteine residues in ODC molecule are implicated in the inactivatory event. 4. When 14C-labeled catechols were used, numerous polypeptides resulted labeled, showing that the reactive quinones formed as intermediates in the process of melanin biosynthesis bind covalently to many cellular proteins.
Gómez-Skarmeta
J L
JL
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Murcia, Spain.
Peñafiel
R
R
Galindo
J D
JD
Lozano
J A
JA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002396:Catechols / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008543:Melanins / Q000096:biosynthesis; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009952:Ornithine / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D010084:Oxidation-Reduction; D010920:Placenta / Q000201:enzymology; D051381:Rats; D013053:Spectrophotometry
D002396:Catechols; D008543:Melanins; D065108:Ornithine Decarboxylase Inhibitors; D009952:Ornithine; D014442:Monophenol Monooxygenase; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid; D004229:Dithiothreitol