Tenhunen R
Ann Clin Res. 1976;8 Suppl 17:2-9.
The conversion of hemoglobin to bilirubin IXalpha in vivo probably proceeds via alpha-hydroxyheme to carbon monoxide and biliverdin-iron complex; after hydrolysis, biliverdin IXalpha is liberated from the iron complex and reduced enzymatically to bilirubin IXalpha. For these reactions molecular oxygen, NADPH and a functioning microsomal electron transport system are needed to generate a reaction radical to transform the heme at the alpha-bridge to alpha-hydroxyheme. After that the reaction proceeds spontaneously. During this reaction sequence heme is readily bound to an insoluble and substrate-inducible protein, which behaves as a stereospecific oxidase. The crucial point in all likelihood is the nature of this heme-binding protein. It seems to be a large protein molecule having a molecular weight in excess of 200,000 and located within the membrane of the endoplasmic reticulum. The conversion of heme to bilirubin has thus some characteristics of nonenzymatic coupled oxidation and, on the other hand, of mixed-function oxidations catalyzed by cytochrome P-450. The exact nature and the regulation of this process, however, appears to be quite different from that manifested with drugs and steroids.
血红蛋白在体内转化为胆红素IXα的过程可能是先通过α-羟基血红素生成一氧化碳和胆绿素-铁复合物；水解后，胆绿素IXα从铁复合物中释放出来，并经酶促还原为胆红素IXα。对于这些反应，需要分子氧、NADPH和一个起作用的微粒体电子传递系统来产生一个反应自由基，将α-桥上的血红素转化为α-羟基血红素。之后反应自发进行。在这个反应序列中，血红素很容易与一种不溶性且受底物诱导的蛋白质结合，该蛋白质表现为立体特异性氧化酶。最关键的一点很可能是这种血红素结合蛋白的性质。它似乎是一个分子量超过200,000的大蛋白质分子，位于内质网的膜内。血红素向胆红素的转化因此具有非酶促偶联氧化的一些特征，另一方面也具有细胞色素P-450催化的混合功能氧化的特征。然而，这个过程的确切性质和调节似乎与药物和类固醇所表现出的情况有很大不同。
