Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia

Abstract

In a patient with nonspherocytic hemolytic anemia, a hexokinase deficiency was detected in the red cells (residual activity about 25% of normal) and in blood platelets (20%-35% of normal activity). Although the total hexokinase activity in lymphocytes was normal, the amount of hexokinase type I was decreased to about 50% of normal. However, the deficiency was compensated for by the appearance of type III hexokinase. Compartmentation studies with controlled digitonin- induced cell lysis showed that this type III enzyme was localized in the cytosol, while almost all hexokinase activity in normal lymphocytes is particulate. No abnormal lymphocyte functions could be detected. The patient was homozygous for the defect. The parents and three of five sibs of the patient were apparently heterozygous with residual activities of 50%-67% of normal in their red cells, but did not show any clinical signs of hexokinase deficiency. The variant enzyme had a slightly decreased affinity for MgATP2- and a strongly increased inhibition constant for glucose-1,6-P2. Affinity for glucose, heat stability, and pH optimum were normal. In the electrophoretic pattern of red cell hexokinase, only one subtype of hexokinase I could be detected, while in normal red cells, at least three subtypes are present. In the heterozygous individuals, no enzymatic abnormalities could be detected, except for an aberration in the electropherogram of one sib.

Characteristics of hexokinase, pyruvate kinase, and glucose‐6‐phosphate dehydrogenase during adult and neonatal reticulocyte maturation

“…In addition, it should be noted that the almost linear increase in the activities of HK, PK, and G6PD with increasing reticulocyte counts may interfere in the diagnosis of enzyme deficiencies of these three enzymes, at least when they are attended with reticulocytosis. In some individual cases of HK and PK deficiency, reticulocyte counts up to 70-80 % have been reported [26,27]. Dependent on the degree of reticulocytosis, normal or even increased activities can be found when compared with normal controls.…”

Use of Mathematical Models for Predicting the Metabolic Effect of Large‐Scale Enzyme Activity Alterations

“…Calculated range of disease Properties of deficient enzymes Number of References diseased minimum range of minimum enzyme unstable kinetic change in persons survival chronic normal activity variants change isoenzyme activity disease activity ? - Tanaka, 1990;Valentine, 1983;Board, 1978;Rijksen, 1983;Miwa, 1985;Paglia, 1981;Necheles, 1970Tanka, 1990Paglia, 1974;Zanella, 1980;Neubauer, 1990;Arnold, 1973Tanka, 1990Vora, 1983;Valentine, 1984 ;Fogelfeld, 1990Kishi, 1987Miwa, 1981 ;Valentine, 1984Eber, 1979Valentine, 1984;Rosa, 1985 ;Zanella, 1985Waller, 1974Tanaka, 1990Maeda, 1991 ;Fujii, 1980Fujii, , 1992Valentine, 1984Schroter, 1965Rosa, 1973Rosa, , 1978Buc, 1974;Rosa, 1989;Tanaka, 1990 Syllm- Rapoport, 1965…”

Enzyme activities of cultured erythroblasts

“…In addition, erythrocyte hexokinase is regulated by phosphorylated hexoses [ 161, ATP, and 2,3-DPG [ 171, which are highly contained in the younger erythrocytes [4,6]. Although some subtypes in type I isozyme of hexokinase exist [ 18,191, erythroblasts and erythrocytes had type I isozyme, the predominant type in the mammalian tissues [18,19].…”