Effect of cobalt on synthesis of heme and cytochrome P-450 in the liver. Studies of adult rat hepatocytes in primary monolayer culture and in vivo.
Effect of cobalt on synthesis of heme and cytochrome P-450 in the liver. Studies of adult rat hepatocytes in primary monolayer culture and in vivo.
复制标题
钴对肝脏中血红素和细胞色素 P-450 合成的影响。
DOI：
10.1016/s0021-9258(17)33313-6
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发表时间：
1976
期刊：
影响因子：
--
通讯作者：
D. Bissell
中科院分区：
文献类型：
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作者：
P. Guzelian;D. Bissell
在原代单层培养的成年大鼠肝细胞中研究了血红素和细胞色素P-450的合成。与对照条件下孵育的细胞相比，用δ-氨基乙酰丙酸孵育的细胞增加了细胞血红素和细胞色素P-450。血红素的形成与培养基中δ-氨基乙酰丙酸的浓度成比例，并且是不饱和的。相比之下，细胞色素P-450的形成是饱和的;过量的细胞内血红素在420 nm处的一氧化碳还原差谱中出现新的吸收带。我们研究了钴对血红素和血红素蛋白形成的影响。金属块形成的细胞色素P-450，但不影响血红素合成。与以前的研究结果与分离的线粒体，没有钴原卟啉形成的金属存在下培养的肝细胞。在大鼠体内研究中，证实给予δ-氨基[14 C]乙酰丙酸后，钴可以减少肝脏中[14 C]血红素的量。然而，目前的研究结果表明，钴的这种作用代表了新标记的肝血红素的加速分解，而不是抑制合成。我们的结论是，钴干扰细胞色素P-450的形成，而不是通过直接抑制血红素的合成，但最有可能通过阻断血红素和脱辅基细胞色素的协会。
Synthesis of heme and cytochrome P-450 have been studied in adult rat hepatocytes in primary monolayer culture. Incubation of cells with delta-aminolevulinic acid increases both cellular heme and cytochrome P-450 relative to that found in cells incubated under control conditions. Formation of heme is proportional to the concentration of delta-aminolevulinic acid in the culture medium and is not saturable. By contrast, formation of cytochrome P-450 is saturable; excess intracellular heme appears as a new absorption band at 420 nm in the carbon monoxide-reduced difference spectrum. We have studied the effect of cobalt on heme and hemoprotein formation in this cell system. The metal blocks formation of cytochrome P-450 but fails to affect heme synthesis. In contrast to previous findings with isolated mitochondria, no cobalt protoporphyrin formed in hepatocytes cultured in the presence of the metal. In studies of rats in vivo, it was confirmed that cobalt acts to reduce the amount of [14C]heme in the liver after administration of delta-amino[14C]levulinic acid. However, the present findings suggest that this effect of cobalt represents accelerated breakdown of newly labeled hepatic heme rather than inhibition of synthesis. We conclude that cobalt interferes with formation of cytochrome P-450 not by direct inhibition of heme synthesis but most likely by blocking the association of heme and apocytochrome.