Transferrin の鉄含量による Heterogeneity と機能的差異に関する研究

Transferrin is a serum glycoprotein which carries inorganic iron for hemoglobin synthesis in erythroid precursor cells. Each transferrin has two iron binding sites in the C- and N-terminal lobes. By 6 M urea/ polyacrylamide gel electrophoresis, transferrin molecules can be separated into four forms, namely apotransferrin, N-site bound monoferric transferrin, C-site bound monoferric transferrin and diferric transferrin according to the different iron distributions. In the present paper, we evaluated the composition of transferrins with different iron contents and examined the usefulness of the concentration of serum diferric transferrin and diferric transferrin uptake (DTU), a new index of ferrokinetics. The results obtained were as follows; (1) Serum transferrin saturation derived from 6 M urea/polyacrylamide gel electrophoresis-counter immunoelectrophoresis was equal to that from serum iron and total iron binding capacity. (2) Apotransferrin, total monoferric transferrin (sum of C-site bound and N-site bound monoferric transferrin) and diferric transferrin in different transferrin saturation had a random distribution of iron. (3) The ratio between the C-site bound and N-site bound monoferric transferrin was distributed between 0.01 and 0.39. The N-site bound monoferric transferrin was dominant in all the different transferrin saturation. The maximum C/N ratio (0.29±0.08) was observed in the normal transferrin saturation (20-30%) and lower values were obtained in patients with iron deficiency (0.14±0.05) and iron overload (0.02±0.01). (4) The mean value of serum diferric transferrin in normal subjects was 1.10±0.49 μmole/l wb. The value in patients with iron deficiency anemia was 1/3 of the value in normal subjects. In patients with aplastic anemia, myelodysplastic syndrome and hemolytic anemia, the mean value was 8.2 times, 8.4 times and 12.3 times higher than that of normal subjects. These differences between normal subjects and patients with various anemias were more significant than those determined by serum iron or transferrin saturation.? (5) The mean value of diferric transferrin uptake (DTU) derived from ferrokinetics measurement was 53.6±1.79 μmole/l wb/day in normal subjects. In patients with iron deficiency anemia, aplastic anemia, myelodysplastic syndrome and hemolytic anemia, the mean value was 111.8±25.5 μmole/l wb/ day, 19.3±15.9 μmole/l wb/day, 55.0±11.3 μmole/l wb/day and 284.8 μmole/l wb/day, respectively. A significant difference was obtained between all the groups except normal subjects and those suffering from myelodysplastic syndrome. The difference between aplastic anemia and myelodysplastic syndrome was prominent, although this discrimination was not obtained by using conventional ferrokinetic parameters such as PIT and %RCU. (6) The combination of diferric transferrin concentration and diferric transferrin uptake gave a clear discrimination between the groups of normal subjects, iron deficiency anemia, aplastic anemia, myelodysplastic syndrome and hemolytic anemia, compared with the combination of serum iron and PIT