Korolnek Tamara, Hamza Iqbal
Department of Animal & Avian Sciences, University of Maryland, College Park MD, USA ; Department of Cell Biology & Molecular Genetics, University of Maryland, College Park MD, USA.
Front Pharmacol. 2014 Jun 4;5:126. doi: 10.3389/fphar.2014.00126. eCollection 2014.
Heme is an iron-containing porphyrin ring that serves as a prosthetic group in proteins that function in diverse metabolic pathways. Heme is also a major source of bioavailable iron in the human diet. While the synthesis of heme has been well-characterized, the pathways for heme trafficking remain poorly understood. It is likely that heme transport across membranes is highly regulated, as free heme is toxic to cells. This review outlines the requirement for heme delivery to various subcellular compartments as well as possible mechanisms for the mobilization of heme to these compartments. We also discuss how these trafficking pathways might function during physiological events involving inter- and intra-cellular mobilization of heme, including erythropoiesis, erythrophagocytosis, heme absorption in the gut, as well as heme transport pathways supporting embryonic development. Lastly, we aim to question the current dogma that heme, in toto, is not mobilized from one cell or tissue to another, outlining the evidence for these pathways and drawing parallels to other well-accepted paradigms for copper, iron, and cholesterol homeostasis.
血红素是一种含铁的卟啉环，作为辅基存在于参与多种代谢途径的蛋白质中。血红素也是人类饮食中生物可利用铁的主要来源。虽然血红素的合成已得到充分表征，但血红素运输途径仍知之甚少。由于游离血红素对细胞有毒，血红素跨膜运输可能受到高度调节。本综述概述了将血红素输送到各种亚细胞区室的需求，以及血红素向这些区室转运的可能机制。我们还讨论了这些运输途径在涉及细胞间和细胞内血红素动员的生理事件（包括红细胞生成、红细胞吞噬、肠道血红素吸收以及支持胚胎发育的血红素运输途径）中可能如何发挥作用。最后，我们旨在质疑目前认为血红素总体上不会从一个细胞或组织转移到另一个细胞或组织的教条，概述这些途径的证据，并将其与其他已被广泛接受的铜、铁和胆固醇稳态范式进行比较。
