THE FORMATION OF ALTERED HEME PRODUCTS BY HUMAN HEMOGLOBIN

通常认为，通过过氧化氢或过氧化氢的氧化改性是有效的。 脂质过氧化物导致各种血红素蛋白失活，包括 肌红蛋白血红蛋白和细胞色素P-450 最近，工作 美国国立卫生研究院的Y Osawa博士报告显示， 当量的过氧化氢与肌红蛋白交联， 一个完整的血红素部分 这种改变的血红蛋白已经被 显示具有氧化酶样活性。 肌红蛋白的改变， 一种能形成有毒氧代谢物的酶可能具有病理性 重要性，特别是在缺血引起的心肌损伤中， 再灌注 这促使我们提出一个问题， 作为血液替代品开发的修饰血红蛋白经历类似的 结构和/或酶修饰，这可以解释，至少在 部分，一些与血红蛋白输注相关的毒性- 基础产品如血管痉挛和复氧损伤。 结果 从我们最近与大泽博士的合作中， 表明用低水平过氧化氢处理血红蛋白 产生可溶性蛋白结合血红素产物， 类似于肌红蛋白。 此外，血红蛋白在α-交联 亚基表现出典型的倾向，氧化修饰比其他 血红蛋白修饰的形式。 血红素衍生的加合物从 过氧化氢与血红蛋白的反应显示很少或没有酶促反应。 在NADPH-心肌黄酶高铁血红蛋白还原酶系统中的活性。 工作是 正在进行各种生理学上的酶活性测试， 相关的还原系统。

It is generally thought that oxidative modification by hydrogen peroxide or lipid peroxide lead to the inactivation of various hemoproteins, including myoglobin, hemoglobin and cytochrome P-450. Recently, however, work reported by Dr. Y Osawa at the NIH showed that addition of 1-2.5 equivalents of hydrogen peroxide to myoglobin resulted in cross-linking of an intact heme moiety to the protein. This altered hemoprotein has been shown to exhibit an oxidase-like activity. The alterations of myoglobin to an enzyme that can form toxic oxygen metabolites may have pathological importance, especially in myocardial injury caused by ischemia and reperfusion. This prompted us to ask the question of whether chemically modified hemoglobins developed as blood substitutes undergo similar structural and/or enzymatic modifications which may explain, at least in part, some of the toxicities associated with the infusion of hemoglobin- based products such as vasospasm and reoxygenation injury. Results transpired so far from our recent collaborative work with Dr. Osawa indicate that treatment of hemoglobin with low levels of hydrogen peroxide produced soluble protein-bound heme products that are chromatographically similar to that of myoglobin. Moreover, hemoglobins cross-linked at alpha subunits showed a typical propensity to oxidative modification than other forms of hemoglobin modifications. The heme derived adducts from the reaction f hydrogen peroxide with hemoglobin showed little or no enzymatic activity in the NADPH-diaphorase methemoglobin reductase system. Work is under way to test for enzymatic activity in a variety of physiologically relevant reducing systems.