Miura T, Muraoka S, Fujimoto Y
Hokkaido College of Pharmacy, Otaru, Japan.
Chem Biol Interact. 1999 Nov 15;123(1):51-61. doi: 10.1016/s0009-2797(99)00124-6.
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.
我们研究了在高铁肌红蛋白（ferrylMb）存在的情况下，多巴和多巴胺对肌酸激酶（CK）活性的影响。在ferrylMb存在时，CK被多巴和多巴胺强烈抑制。多巴和多巴胺显著促进ferrylMb还原为高铁肌红蛋白（metMb）。来自多巴和多巴胺的半醌可能参与了CK的失活。在酶失活过程中，动力学参数Vmax和Km均发生了变化。此外，还原型谷胱甘肽在早期恢复了CK的活性。这些结果表明，CK的失活主要是由于酶的巯基（SH）基团被氧化。其他儿茶酚，如肾上腺素和去甲肾上腺素，对CK活性的失活作用很小，而它们促进了ferrylMb还原为metMb。其他含SH的酶，包括乙醇脱氢酶（ADH）和甘油醛-3-磷酸脱氢酶（GAPDH），在ferrylMb存在的情况下被多巴和多巴胺失活的程度较小。肾上腺素和去甲肾上腺素并不能显著阻止ADH的失活，对GAPDH的抑制作用非常微弱。这些结果表明，在ferrylMb存在的情况下，多巴和多巴胺作为促氧化剂使含SH的酶失活。
