Nagababu Enika, Rifkind Joseph M
Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Antioxid Redox Signal. 2004 Dec;6(6):967-78. doi: 10.1089/ars.2004.6.967.
Heme proteins play a major role in various biological functions, such as oxygen sensing, electron transport, signal transduction, and antioxidant defense enzymes. Most of these reactions are carried out by redox reactions of heme iron. As the heme is not recycled, most cells containing heme proteins have the microsomal mixed function oxygenase, heme oxygenase, which enzymatically degrades heme to biliverdin, carbon monoxide, and iron. However, the red cell with the largest pool of heme protein, hemoglobin, contains no heme oxygenase, and enzymatic degradation of the red cell heme occurs only after the senescent red cells are removed by the reticuloendothelial system. Therefore, only nonenzymatic heme degradation initiated when the heme iron undergoes redox reactions in the presence of oxygen-producing reactive oxygen species takes place in the red cell. Unlike enzymatic degradation, which specifically attacks the alpha-methene bridge, reactive oxygen species randomly attack all the carbon methene bridges of the tetrapyrrole rings, producing various pyrrole products in addition to releasing iron. This review focuses on the literature related to nonenzymatic heme degradation with special emphasis on hemoglobin, the dominant red cell heme protein.
血红素蛋白在多种生物学功能中发挥着重要作用，如氧气感知、电子传递、信号转导以及抗氧化防御酶。这些反应大多通过血红素铁的氧化还原反应来进行。由于血红素无法循环利用，大多数含有血红素蛋白的细胞都具有微粒体混合功能氧化酶——血红素加氧酶，该酶可将血红素酶解为胆绿素、一氧化碳和铁。然而，血红素蛋白含量最高的红细胞，即血红蛋白，却不含血红素加氧酶，红细胞血红素的酶解仅在衰老红细胞被网状内皮系统清除后才会发生。因此，在红细胞中，只有当血红素铁在产生活性氧的氧气存在下发生氧化还原反应时引发的非酶促血红素降解才会发生。与特异性攻击α-次甲基桥的酶促降解不同，活性氧会随机攻击四吡咯环的所有碳次甲基桥，除了释放铁之外，还会产生各种吡咯产物。本综述重点关注与非酶促血红素降解相关的文献，特别强调血红蛋白，即红细胞中占主导地位的血红素蛋白。
