Kools A M, Straka J G, Hill H D, Whitmer D I, Holman R T, Bloomer J R
Liver Center, University of Minnesota, Minneapolis 55455.
Hepatology. 1989 Apr;9(4):557-61. doi: 10.1002/hep.1840090409.
Ferrochelatase is an enzyme bound to the inner mitochondrial membrane, which is important in heme biosynthesis. Activity of purified ferrochelatase is affected by the presence of certain fatty acids. In the present study, we examined whether the activity of ferrochelatase is altered by dietary manipulation of the composition of mitochondrial membrane phospholipid fatty acyl groups. Rats were fed diets containing triolein, safflower or menhaden oil as 5% (w/w) of the diet. After 3 weeks, the animals were killed and liver mitochondria were isolated. Phospholipid fatty acid composition and ferrochelatase activity were assayed in the isolated mitochondria. Marked differences were seen. The proportion of oleic acid was highest in the triolein oil-fed group, that of linoleic and arachidonic acid was highest in the safflower oil-fed group and the proportion of eicosapentaenoic acid was highest in the menhaden oil-fed group. Ferrochelatase activity was greatest in the triolein oil-fed group and lowest in the menhaden oil-fed group regardless of whether the mitochondria were intact, sonicated or sonicated and treated with Tween 20. Mixing of mitochondria from menhaden oil-fed rats with triolein oil resulted in a significant increase in ferrochelatase activity. Membrane fluidity and activities of the mitochondrial membrane enzymes succinic dehydrogenase and cytochrome oxidase did not differ among the groups. We conclude that dietary manipulation of mitochondrial membrane phospholipid fatty acyl group composition can directly modulate hepatic ferrochelatase activity. This has potential application in the treatment of protoporphyria, the genetic disorder in which ferrochelatase activity is deficient.
铁螯合酶是一种结合于线粒体内膜的酶，在血红素生物合成中起重要作用。纯化的铁螯合酶的活性受某些脂肪酸的影响。在本研究中，我们检测了通过饮食调控线粒体膜磷脂脂肪酸酰基组成是否会改变铁螯合酶的活性。给大鼠喂食含有三油酸甘油酯、红花油或鲱鱼油的饲料，这些油占饲料的5%（w/w）。3周后，处死动物并分离肝脏线粒体。测定分离出的线粒体中的磷脂脂肪酸组成和铁螯合酶活性。结果发现了显著差异。在喂食三油酸甘油酯油的组中油酸比例最高，在喂食红花油的组中亚油酸和花生四烯酸比例最高，在喂食鲱鱼油的组中二十碳五烯酸比例最高。无论线粒体是完整的、经超声处理的还是经超声处理并用吐温20处理的，铁螯合酶活性在喂食三油酸甘油酯油的组中最高，在喂食鲱鱼油的组中最低。将喂食鲱鱼油的大鼠的线粒体与三油酸甘油酯油混合会导致铁螯合酶活性显著增加。各组之间线粒体膜流动性以及线粒体膜酶琥珀酸脱氢酶和细胞色素氧化酶的活性没有差异。我们得出结论，通过饮食调控线粒体膜磷脂脂肪酸酰基组成可以直接调节肝脏铁螯合酶活性。这在治疗原卟啉症（一种铁螯合酶活性缺乏的遗传性疾病）方面具有潜在应用价值。
