EFFECT OF LEAD AND GENETIC FACTORS ON HEME BIOSYNTHESIS IN THE HUMAN RED CELL *
EFFECT OF LEAD AND GENETIC FACTORS ON HEME BIOSYNTHESIS IN THE HUMAN RED CELL *
复制标题
铅和遗传因素对人红细胞血红素生物合成的影响*
DOI：
--
复制
发表时间：
1975
影响因子：
5.2
通讯作者：
A. Kappas
中科院分区：
文献类型：
--
作者：
Shigeru Sassa;S. Granick;A. Kappas
血红素用作许多血红素蛋白的辅基，例如，血红蛋白、肌红蛋白、过氧化氢酶、过氧化物酶、细胞色素和色氨酸吡咯酶。血红素具有三种重要的生物学功能：（1）血红素是氧转运的辅基。(2)作为细胞色素α 1的一部分，它在电子传递中起重要作用。(3)最后，作为细胞色素P-450的一部分，它参与肝脏、肾上腺皮质、肺和胎盘中多种化合物的解毒。我们已经开发了灵敏的方法来研究血红素生物合成链的中间体和酶。通过这些方法，我们试图研究环境化学品或药物的影响，以及遗传缺陷，这些缺陷导致血红素途径的缺陷，从而导致O 2运输，氧化代谢和解毒的病理学。我们在本文中审查：（1）我们最近的微量测定方法，只需要微升全血;这些方法包括测定红细胞原卟啉（EP）、6-氨基乙酰丙酸酯酶（ALA-D）活性和尿卟啉原合成酶（URO-S）活性;（2）这些方法在人类遗传研究中的应用;（3）铅对EP和ALA-D活性的影响以及铅对ALA-D活性抑制的性质。此外，我们报告了我们的研究进展，URO-S在培养的人羊膜细胞。
Heme functions as a prosthetic group for a number of hemoproteins, e.g., hemoglobin, myoglobin, catalase, peroxidases, cytochromes, and tryptophan pyrrolase. Heme has three important biologic functions: (1) I t serves as a prosthetic group for oxygen transport. (2) As part of mitochondria1 cytochromes, it plays an important role in electron transport. (3) Finally, as part of cytochrome P-450, it is involved in the detoxification of a variety of compounds in the liver, adrenal cortex, lung, and placenta. We have developed sensitive methods t o study the intermediates and enzymes of the heme biosynthetic chain. With these methods, we are attempting t o study effects of environmental chemicals or drugs, and genetic defects, that result in defects of the heme pathway which lead t o pathologies of 0 2 transport, of oxidative metabolism, and of detoxification. We review in this paper: ( I ) our recent microassay methods that require only microliters of whole blood; these include assays for erythrocyte protoporphyrin (EP), 6-aminolevulinate dehydratase (ALA-D) activity, and uroporphyrinogen synthetase (URO-S) activity; ( 2 ) applications of these methods to human genetic studies; and (3) the effect of lead on EP and ALA-D activity as well as the nature of lead inhibition on ALA-D activity. In addition, we report our progress on studies of URO-S in human amniotic cells in culture.