Abstract
Erythrocyte membrane leakage of Ca2+ in familial phosphofructokinase deficiency results in a compensatory increase of Ca2+-ATPase activity that depletes ATP and leads to diminished erythrocyte deformability and a higher rate of hemolysis. Lowered ATP levels in circulating erythrocytes are accompanied by increased IMP, indicating that activated AMP deaminase plays a role in this metabolic dysregulation. Exposure to a calmodulin antagonist significantly slows IMP accumulation during experimental energy imbalance in patients' cells to levels that are similar to those in untreated controls, implying that Ca2+-calmodulin is involved in erythrocyte AMP deaminase activation in familial phosphofructokinase deficiency. Therapies directed against activated isoform E may be beneficial in this compensated anemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP Deaminase / blood*
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Adenosine Triphosphate / biosynthesis
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Adenosine Triphosphate / blood
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Anemia, Hemolytic, Congenital / blood
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Anemia, Hemolytic, Congenital / enzymology
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Anemia, Hemolytic, Congenital / etiology*
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Calcium / physiology*
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Calcium-Transporting ATPases / blood
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Calmodulin / antagonists & inhibitors
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Calmodulin / blood*
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Cell Membrane Permeability
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Enzyme Activation
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Erythrocyte Deformability
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Erythrocytes / enzymology*
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Glycogen Storage Disease Type VII / blood*
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Glycogen Storage Disease Type VII / genetics
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Glycolysis
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Humans
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Hypoxanthine / blood
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Inosine Monophosphate / blood
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Isoenzymes / blood
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Models, Biological
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p-Methoxy-N-methylphenethylamine / pharmacology
Substances
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Calmodulin
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Isoenzymes
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Inosine Monophosphate
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Hypoxanthine
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p-Methoxy-N-methylphenethylamine
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Adenosine Triphosphate
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AMP Deaminase
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Calcium-Transporting ATPases
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Calcium