Deficiencies of glycolytic enzymes as a possible cause of hemolytic anemia

• Published in: Biochimica et biophysica acta Vol. 1474; no. 1; pp. 75 - 87
• Main Authors: Martinov, Michael V., Plotnikov, Andrew G., Vitvitsky, Victor M., Ataullakhanov, Fazoil I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 06.03.2000
• Subjects: Adenosine Triphosphate - metabolism; Aldehyde Dehydrogenase - deficiency; Anemia, Hemolytic - blood; Anemia, Hemolytic - etiology; Cell Survival; Energy Metabolism; Enzyme deficiency; Enzymes - deficiency; Erythrocyte; Erythrocyte Volume; Erythrocytes - enzymology; Glycolysis; Hemolytic anemia; Hexokinase - deficiency; Humans; L-Lactate Dehydrogenase - deficiency; Mathematical model; Models, Biological; Pyruvate Kinase - deficiency; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; NADH, nicotinamide adenine dinucleotide reduced; Enzyme deficiency; ENO, enolase; GAP, glyceraldehyde-3-phosphate; LAC, lactate; NAD, nicotinamide adenine dinucleotide oxidized; 2,3-DPG, 2,3-diphosphoglycerate; PFK, phosphofructokinase; 3-PG, 3-phosphoglycerate; PO4, orthophosphate; Hemolytic anemia; GPI, glucosephosphate isomerase; G6P, glucose-6-phosphate; TPI, triosephosphate isomerase; DPGM, diphosphoglycerate mutase; AMPD, AMP deaminase; Mathematical model; PEP, phosphoenolpyruvate; ATP, adenosine triphosphate; DAP, dihydroxyacetone phosphate; HK, hexokinase; LDH, lactate dehydrogenase; FDP, fructose-1,6-diphosphate; 2-PG, 2-phosphoglycerate; AMP, adenosine monophosphate; GLU, glucose; DPGP, diphosphoglycerate phosphatase; PYR, pyruvate; PGK, phosphoglycerate kinase; Erythrocyte; GAPDH, glyceraldehyde phosphate dehydrogenase; ADP, adenosine diphosphate; PGM, phosphoglycerate mutase; F6P, fructose-6-phosphate; Glycolysis; PK, pyruvate kinase; ALD, aldolase; 1,3-DPG, 1,3-diphosphoglycerate; AMPP, AMP phosphatase; AK, adenylate kinase
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/S0304-4165(99)00218-4

The critical minimum values of Na,K-ATPase and glycolytic enzyme activities at which the erythrocyte viability is lost were calculated using the mathematical model of the erythrocyte, which included all reactions of glycolysis, adenylate metabolism, ionic balance, and osmotic regulation of erythrocyte volume. The criterion for cell death was an increase in its volume to the level at which it is sequestrated from the circulation or is lysed. In hemolytic anemia associated with hexokinase or pyruvate kinase deficiency, activities of these enzymes measured in patient erythrocytes appeared to be close to the calculated critical values. By contrast, in hemolytic anemia associated with phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase deficiency, activities of these enzymes measured in patient erythrocytes were significantly greater than the calculated critical values. In this case, if the deficient enzyme were stable, i.e. its activity in the cell were low, but constant in time, the deficiency observed would not account for the erythrocyte destruction observed and the development of hemolytic anemia. It was shown, however, that in phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase deficiency, hemolytic anemia can arise because of the instability of these enzymes in time.