Inactivation of creatine kinase induced by dopa and dopamine in the presence of ferrylmyoglobin.
We investigated the effect of dopa and dopamine on creatine kinase (CK) activity in the presence of ferrylmyoglobin (ferrylMb). CK was sharply inhibited by dopa and dopamine in the presence of ferrylMb. Dopa and dopamine markedly promoted the reduction of ferrylMb to metmyoglobin (metMb). The semiquinone from dopa and dopamine may be involved in CK inactivation. During inactivation of the enzyme, both kinetic parameters Vmax and Km changed. In addition, reduced glutathione restored the activity of CK at an early stage. These results suggest that inactivation of CK is dominantly due to oxidation of sulfhydryl (SH) groups of the enzyme. Other catechols, such as adrenaline and noradrenaline, little inactivated CK activity, whereas they promoted the reduction of ferrylMb to metMb. Other SH enzymes, including alcohol dehydrogenase (ADH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were inactivated to a lesser extent by dopa and dopamine in the presence of ferrylMb. Adrenaline and noradrenaline did not significantly prevent the inactivation of ADH and very slightly inhibited GAPDH. These results suggest that dopa and dopamine act as prooxidants to inactivate SH enzymes in the presence of ferrylMb.
Miura
T
T
Hokkaido College of Pharmacy, Otaru, Japan. miurat@hokuyakudai.ac.jp
Muraoka
S
S
Fujimoto
Y
Y
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D006736:Horses; D008786:Metmyoglobin / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; C028048:ferrylmyoglobin; D008786:Metmyoglobin; D004295:Dihydroxyphenylalanine; D000426:Alcohol Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003402:Creatine Kinase; D004298:Dopamine