Ajioka Richard S, Phillips John D, Kushner James P
Department of Internal Medicine, Division of Hematology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Biochim Biophys Acta. 2006 Jul;1763(7):723-36. doi: 10.1016/j.bbamcr.2006.05.005. Epub 2006 Jun 3.
Most iron in mammalian systems is routed to mitochondria to serve as a substrate for ferrochelatase. Ferrochelatase inserts iron into protoporphyrin IX to form heme which is incorporated into hemoglobin and cytochromes, the dominant hemoproteins in mammals. Tissue-specific regulatory features characterize the heme biosynthetic pathway. In erythroid cells, regulation is mediated by erythroid-specific transcription factors and the availability of iron as Fe/S clusters. In non-erythroid cells the pathway is regulated by heme-mediated feedback inhibition. All of the enzymes in the heme biosynthetic pathway have been crystallized and the crystal structures have permitted detailed analyses of enzyme mechanisms. All of the genes encoding the heme biosynthetic enzymes have been cloned and mutations of these genes are responsible for a group of human disorders designated the porphyrias and for X-linked sideroblastic anemia. The biochemistry, structural biology and the mechanisms of tissue-specific regulation are presented in this review along with the key features of the porphyric disorders.
哺乳动物系统中的大多数铁被输送到线粒体，作为亚铁螯合酶的底物。亚铁螯合酶将铁插入原卟啉IX中形成血红素，血红素被整合到血红蛋白和细胞色素中，这是哺乳动物中主要的血红素蛋白。组织特异性调节特征是血红素生物合成途径的特点。在红细胞中，调节由红细胞特异性转录因子和作为铁硫簇的铁的可用性介导。在非红细胞中，该途径由血红素介导的反馈抑制调节。血红素生物合成途径中的所有酶都已结晶，晶体结构允许对酶机制进行详细分析。所有编码血红素生物合成酶的基因都已被克隆，这些基因的突变导致了一组被称为卟啉症的人类疾病以及X连锁铁粒幼细胞贫血。本综述介绍了生物化学、结构生物学以及组织特异性调节的机制，以及卟啉症疾病的关键特征。
