Erythrocyte pyruvate kinase deficiency: A kinetic method for differentiation between heterozygosity and compound-heterozygosity
- 1 August 1989
- journal article
- research article
- Published by Wiley in American Journal of Hematology
- Vol. 31 (4) , 225-232
- https://doi.org/10.1002/ajh.2830310402
Abstract
The goal of the present study was to search for criteria that allow one to distinguish between normal individuals and heterozygotes as well as compound heterozygotes for pyruvate kinase (PK) deficiency. As the residual activity of PK with heterozygotes was between 35% and 110% of the normal activity, it was necessary to find other methods to prove heterozygosity. The PK in the hemolysates of 23 patients suffering from PK deficiency, 36 paternal and maternal enzymes as well as the enzymes of five heterozygous and four normal siblings together with those of 20 normal individuals, were studied according to the recommendations of the International Committee for Standardization in Haematology. The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up‐to‐twofold increase of the intracellular concentrations of glucose‐6‐phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)‐binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. The most significant criterium found with all heterozygotes was a mixed cooperativity of the PEP‐binding process caused by the presence of a mixture of normal and mutant PK.Keywords
This publication has 16 references indexed in Scilit:
- HOW DO RED CELL ENZYMES AGE? HYPOTHESIS AND FACTSBritish Journal of Haematology, 1986
- Characteristics of hexokinase, pyruvate kinase, and glucose‐6‐phosphate dehydrogenase during adult and neonatal reticulocyte maturationAmerican Journal of Hematology, 1985
- Pyruvate kinase “Göttingen1,2”: Congenital hemolytic anemia, evidence of double heterozygosity, and lack of enzyme cooperativityHuman Genetics, 1982
- Red cell pyruvate kinase deficiency: An optimised assayClinica Chimica Acta; International Journal of Clinical Chemistry, 1980
- Recommended Methods for the Characterization of Red Cell Pyruvate Kinase Variants.British Journal of Haematology, 1979
- International Committee for Standardization in Haematology: Recommended Methods for Red‐Cell Enzyme Analysis*British Journal of Haematology, 1977
- A computer program for the determination of kinetic parameters from sigmoidal steady‐state kineticsFEBS Letters, 1970
- Non-Inverted Versus Inverted Plots in Enzyme KineticsNature, 1959
- THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONSAnnals of the New York Academy of Sciences, 1949
- The Determination of Enzyme Dissociation ConstantsJournal of the American Chemical Society, 1934