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Pyruvate kinase hyperactivity genetically determined metabolic consequences and molecular characterization
Insights
Red blood cell pyruvate kinase (PK) hyperactivity in a family was linked to low 2,3-diphosphoglycerate (2,3-DPG) and high adenosine triphosphate (ATP) levels. This hyperactivity, characterized by abnormal PK electrophoretic patterns, suggests a novel enzyme variant impacting red cell metabolism.
Area of Science:
- Biochemistry
- Hematology
- Genetics
Background:
- Red blood cell (RBC) pyruvate kinase (PK) is crucial for glycolysis.
- Deficiencies in PK activity cause hemolytic anemia.
- This study investigates a family with apparent PK hyperactivity.
Purpose of the Study:
- To characterize the red cell pyruvate kinase (PK) defect in a family.
- To investigate the biochemical and molecular basis of the observed PK hyperactivity.
- To understand the metabolic consequences of this enzyme abnormality.
Main Methods:
- Analysis of red cell metabolism in vitro.
- Electrophoretic characterization of pyruvate kinase (PK) activity.
- Biochemical assays including thermolability and immunological reactivity.
- Determination of 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) levels.
Main Results:
- Subjects exhibited red cell pyruvate kinase (PK) hyperactivity.
- Low 2,3-diphosphoglycerate (2,3-DPG) and high adenosine triphosphate (ATP) levels were observed.
- Abnormal PK electrophoretic patterns with additional bands, including one migrating like PKM2.
- The identified PK variant was thermounstable and immunologically similar to PKM2.
Conclusions:
- A novel red cell pyruvate kinase (PK) hyperactivity variant is described.
- This variant leads to altered red cell energy metabolism.
- The findings highlight the complex relationship between PK activity, 2,3-DPG, and ATP levels in red blood cells.
Abstract:
Four people from the same family with red cell pyruvate kinase (PK) hyperactivity are described. These people displayed low 2,3-diphosphoglycerate (2,3-DPG) and high adenosine triphosphate (ATP) levels. In vitro metabolism studies of their red cells showed the relationship between the PK activity, low 2,3-DPG, and high ATP levels. The PK electrophoretic pattern of these subjects was abnormal by the presence of several additional bands; one of them migrated like PKM2. PKR from these people was thermounstable and M2-like PK was identical to PKM2 for immunologic reactivity and KO, 5s for phosphoenolpyruvate.