Unstable variant of NADH methemoglobin reductase in Puerto Ricans with hereditary methemoglobinemia.
نویسندگان
چکیده
The electrophoretic mobility of erythrocyte NADH methemoglobin reductase in five hereditary methemoglobinemia patients from three Puerto Rican kindreds was 118% of normal at pH 8.6. The methemoglobin ferrocyanide reductase activity of the enzyme in erythrocyte hemolysates was 3.2-6.4% of normal. Electrophoresis of hemolysates prepared from the blood of patients from two different families at six pH values between 4.6 and 9.3 did not differentiate between the variant enzymes. Examination of the deficient enzymes extracted from the erythrocytes of one patient from each kindred revealed altered affinity for NADH and dichloroindophenol dye and decreased thermal stability. The quantitative similarity of the abnormal findings, together with the Puerto Rican origin of the kindreds, suggested that the cyanotic patients possessed the same abnormal enzyme and were thus homozygous for the same rare mutant gene. Consanguinity of the kindreds could not be established. The rates of decline of the normal and variant NADH methemoglobin reductase enzymes in vivo were measured in erythrocyte fractions of increasing cell age. The rate of decline of the variant enzyme was increased 20-fold by comparison with the normal enzyme. The methemoglobin percentage in erythrocyte fractions of increasing cell age correlated inversely with the activity of the variant. The variant enzyme averaged 37% of normal mean activity in young cells and 1% in old cells. The normal enzyme, on the other hand, lost only one-sixth of its activity as the cells aged, and the methemoglobin content in old normal cells did not rise. These observations support the hypothesis that the deficient activity and the heterogeneous pattern of methemoglobin accumulation in vivo arise principally from the accelerated inactivation of variant NADH methemoglobin reductase during the life-span of the red blood cell.
منابع مشابه
Electrophoretic and functional variants of NADH-methemoglobin reductase in hereditary methemoglobinemia.
The electrophoretic mobility and activity of NADH-methemoglobin reductase in erythrocytes of patients with hereditary methemoglobinemia, obligatory heterozygotes, and normal subjects were examined. Six distinct electrophoretic variants were found in studies of erythrocytes from members of ten different families. Five variants (Boston Slow, Duarte, Princeton, Puerto Rico, and California) were as...
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I would like to add to this well written article that we have also reported acquired methemoglobinemia cases with administration of cytanest in puerperal women with g6PD deficiency and infants in whom erythrocyte cytochrome 65 reductase was assoyed [1-4], which is the main enzyme for methemoglobin reductase in erythrocytes as mentioned by the authors. In addition, hereditary methemoglobinemias ...
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ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 51 6 شماره
صفحات -
تاریخ انتشار 1972