The contribution of Ca+ calmodulin activation of human erythrocyte AMP deaminase (isoform E) to the erythrocyte metabolic dysregulation of familial phosphofructokinase deficiency.

Richard L Sabina, Anders Waldenström, Gunnar Ronquist

Journal: Haematologica 2006;91(5):652-5

PMID: 16670071

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.

Address: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. [email protected]

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MeSH Terms: AMP Deaminase, Adenosine Triphosphate, Anemia, Hemolytic, Congenital, Calcium, Calcium-Transporting ATPases, Calmodulin, Cell Membrane Permeability, Enzyme Activation, Erythrocyte Deformability, Erythrocytes, Glycogen Storage Disease Type VII, Glycolysis, Humans, Hypoxanthine, Inosine Monophosphate, Isoenzymes, Models, Biological, p-Methoxy-N-methylphenethylamine