Phillippy B Q, Graf E
United States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, LA 70124, USA.
Free Radic Biol Med. 1997;22(6):939-46. doi: 10.1016/s0891-5849(96)00342-5.
Iron chelates of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate lacked free coordination sites and prevented the iron-catalyzed oxidation of ascorbic acid and peroxidation of arachidonic acid. In contrast, iron chelates of inositol 1,2,6-trisphosphate and inositol 1,2,5,6-tetrakisphosphate contained available coordination sites, permitted iron-catalyzed ascorbic acid oxidation, and enhanced arachidonic acid peroxidation. It was concluded that the 1,2,3-trisphosphate grouping of inositol hexakisphosphate was responsible for the inhibition of iron-catalyzed hydroxyl radical formation. The structure of the chelate with the phosphates in an axial-equatorial-axial configuration appeared to be the only possible inositol trisphosphate that could form bonds between six oxygen atoms and the six coordination sites on iron. Km values for cleavage by Escherichia coli alkaline phosphatase were as follows: inositol 1,2,3-trisphosphate, 56 microM; inositol 1,2,6-trisphosphate, 35 microM; inositol 1,2,3,6-tetrakisphosphate, 139 microM; and inositol 1,2,5,6-tetrakisphosphate, 100 microM. The initial hydrolysis rates of 200 microM solutions of the latter three isomers by E. coli alkaline phosphatase were not affected by an equimolar concentration of iron, whereas the rate for inositol 1,2,3-trisphosphate decreased in the presence of iron to 50% of the control. Therefore, the antioxidant potential of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate in cells and other biological systems may be fortified by the resistance of their iron chelates to enzymatic hydrolysis of the functional 1,2,3-trisphosphate array.
肌醇1,2,3 - 三磷酸和肌醇1,2,3,6 - 四磷酸的铁螯合物缺乏自由配位位点，可防止铁催化的抗坏血酸氧化和花生四烯酸过氧化。相比之下，肌醇1,2,6 - 三磷酸和肌醇1,2,5,6 - 四磷酸的铁螯合物含有可用的配位位点，允许铁催化抗坏血酸氧化，并增强花生四烯酸过氧化。得出的结论是，肌醇六磷酸的1,2,3 - 三磷酸基团负责抑制铁催化的羟基自由基形成。磷酸盐呈轴向 - 赤道 - 轴向构型的螯合物结构似乎是唯一可能在六个氧原子和铁上的六个配位位点之间形成键的肌醇三磷酸。大肠杆菌碱性磷酸酶切割的Km值如下：肌醇1,2,3 - 三磷酸为56 microM；肌醇1,2,6 - 三磷酸为35 microM；肌醇1,2,3,6 - 四磷酸为139 microM；肌醇1,2,5,6 - 四磷酸为100 microM。后三种异构体的200 microM溶液被大肠杆菌碱性磷酸酶的初始水解速率不受等摩尔浓度铁的影响，而肌醇1,2,3 - 三磷酸在铁存在下的速率降至对照的50％。因此，细胞和其他生物系统中肌醇1,2,3 - 三磷酸和肌醇1,2,3,6 - 四磷酸的抗氧化潜力可能因其铁螯合物对功能性1,2,3 - 三磷酸阵列酶促水解的抗性而得到增强。
