Comparative study of protoporphyrins in erythropoietic protoporphyria and griseofulvin-induced murine protoporphyria. Binding affinities, distribution, and fluorescence spectra in various blood fractions.
Comparative study of protoporphyrins in erythropoietic protoporphyria and griseofulvin-induced murine protoporphyria. Binding affinities, distribution, and fluorescence spectra in various blood fractions.
复制标题
原卟啉在红细胞生成性原卟啉症和灰黄霉素诱导的小鼠原卟啉症中的比较研究。
DOI：
10.1172/jci108787
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发表时间：
1977
期刊：
影响因子：
--
通讯作者：
A. Lamola
中科院分区：
文献类型：
--
作者：
M. Poh;A. Lamola
人类先天性红细胞生成性原卟啉过多和灰黄霉素诱导的小鼠肝原卟啉过多与血红蛋白和基质组分有相似的关系。每例均有99.5%以上的红细胞原卟啉与血红蛋白结合。然而，当测量红细胞中的原卟啉浓度时，发现在不连续的密度梯度上被分成逐渐增长的种群的红细胞中的原卟啉浓度存在着显著的差异。在红细胞生成性原卟啉症中，卟啉含量随着年龄的增长而迅速减少；在小鼠原卟啉症中，老化的红细胞群体逐渐变得更富含卟啉。在体外，原卟啉从血浆中扩散到完整的红细胞膜上。原卟啉与血红蛋白的等摩尔结合亲和力是原卟啉与血清白蛋白结合亲和力的40倍。这种强大的亲和力为观察到的跨膜扩散提供了驱动力，并解释了小鼠肝原卟啉病中红细胞/血浆卟啉比率高的原因。尽管有很强的血红蛋白亲和力，先前在简单的红细胞生成性原卟啉病中显示的红细胞内原卟啉快速流出到血浆中的相反的快速外流仍然发生，这意味着肝脏持续有效地清除血浆中的原卟啉。此外，这些和其他数据表明，在红细胞生成性原卟啉中，任何重要的血液原卟啉的肝脏合成来源都是非常不可能的。
Excess erythrocyte protoporphyrins of human congenital erythropoietic protoporphyria and of griseofulvin-induced murine hepatic protoporphyria were found to be associated with hemoglobin and stroma fractions in similar relationships. More than 99.5% of total erythrocyte protoporphyrin was bound to hemoglobin in each case. However, profound differences were found when protoporphyrin concentration was measured in erythrocytes that had been segregated into populations of progressive age on discontinuous density gradients. In erythropoietic protoporphyria, porphyrin content diminished rapidly with age; in murine protoporphyria, the aging erythrocyte populations became progressively more porphyrin rich. In vitro diffusion of protoporphyrin from plasma across the intact erythrocyte membrane was demonstrated. The equimolar binding affinity of protoporphyrin to hemoglobin was shown to be 40 times that of protoporphyrin to serum albumin. This strong affinity provides the driving force for the observed transmembrane diffusion, and explains the high erythrocyte/plasma porphyrin ratio in murine hepatic protoporphyria. The opposite rapid efflux of intra-erythrocytic protoporphyrin into plasma previously shown in uncomplicated erythropoietic protoporphyria occurs despite this strong hemoglobin affinity, implying continuous efficient clearance of protoporphyrin from plasma by the liver. Furthermore, these and other data suggest that a hepatic synthetic source for any significant fraction of the blood protoporphyrin in erythropoietic protoporphyria is highly improbable.