铁与肝脏：铁负荷对大鼠肝脏血红素合成的急性影响。5-氨基酮戊酸脱水酶活性降低的作用。
Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase.
作者信息
Bonkowsky H L, Healey J F, Sinclair P R, Sinclair J F, Shedlofsky S I, Elder G H
出版信息
J Clin Invest. 1983 May;71(5):1175-82. doi: 10.1172/jci110866.
Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.
通过腹腔注射葡聚糖铁（处死前18 - 20小时，500毫克铁/千克体重）对大鼠进行急性铁负荷处理，结果显示，采用最近描述的肝匀浆检测方法（1981年《生物化学杂志》第198卷，第595 - 604页）测定，5-氨基-[¹⁴C] - 酮戊酸（[¹⁴C]ALA）转化为血红素的速率降低了30%。铁负荷导致标记的ALA转化为血红素的速率降低，这一现象被证明是由于ALA脱水酶活性降低了70 - 80%。铁负荷导致的ALA脱水酶活性降低与肝脏中谷胱甘肽（GSH）浓度降低无关，添加二硫苏糖醇、Zn²⁺或Fe²⁺和Fe³⁺的螯合剂也无法使其逆转。向对照肝脏的匀浆中添加硫酸亚铁、柠檬酸铁或铁蛋白，对ALA脱水酶的活性没有影响。铁负荷导致的ALA脱水酶活性降低与ALA合酶的相应增加呈反向关系。葡聚糖铁增强了烯丙基异丙基乙酰胺对ALA合酶的诱导作用。然而，这种增强作用与铁负荷导致的ALA脱水酶活性降低无关。
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