Control of intracellular heme levels: heme transporters and heme oxygenases.

Control of intracellular heme levels: heme transporters and heme oxygenases.
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DOI:
10.1016/j.bbamcr.2011.01.008
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发表时间:
2011-05
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Quigley JG
Quigley JG
中科院分区:
其他
文献类型:
--
作者:
Khan AA;Quigley JG

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血红素是参与基本生物过程的蛋白质的辅助因子,包括氧化代谢、氧储存和运输、信号转导和药物代谢。此外,血红素对哺乳动物的全身铁稳态也很重要。血红素在细胞生物学中具有重要的调节作用,但过量的细胞内血红素是有毒的;因此,机制已经进化到控制获取,合成,分解代谢和细胞血红素的排出。最近,一些血红素转运体和血红素合成中间体已经被描述。在这里,我们回顾了血红素代谢的各个方面,并讨论了我们目前对血红素转运蛋白的理解,重点是细胞表面血红素输出蛋白FLVCR的功能。在小鼠中,Flvcr的敲低会导致红细胞生成缺陷和全身铁稳态紊乱,这强调了血红素转运体在哺乳动物生理学中的关键作用。
Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number of transporters of heme and heme synthesis intermediates have been described. Here we review aspects of heme metabolism and discuss our current understanding of heme transporters, with emphasis on the function of the cell-surface heme exporter, FLVCR. Knockdown of Flvcr in mice leads to both defective erythropoiesis and disturbed systemic iron homeostasis, underscoring the critical role of heme transporters in mammalian physiology.
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