title: The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy.
abstract: Normal human erythrocyte phosphofructokinase (ATP: D-fructose-6, P-1-phosphotransferase, EC 2.7.1.11; PFK) has recently been shown to consist of a heterogeneous mixture of five tetrameric isozymes: M4, M3L, M2L2, ML3, and L4 (M, muscle type; L, liver type). In the light of these findings, we have investigated the molecular basis of the inherited erythrocyte PFK deficiency associated with myopathy and hemolysis (Tarui disease). The propositus, a 31-yr-old male, suffered from muscle weakness and myoglobinuria on exertion. He showed mild erythrocytosis despite laboratory evidence of hemolysis. In his erythrocytes a metabolic crossover point was found at the level of PFK; 2,3-diphosphoglycerate (2,3-DPG) was also significantly reduced. The PFK from the patient's erythrocytes consisted exclusively of the L4 isozyme, and there was a complete absence of the other four. The leukocyte and platelet PFKs from the patient showed normal activities, chromatographic profiles, and precipitation with anti-M4 antibody. These studies provide direct evidence that in Tarui disease the M-type subunits are absent; but the liver- and platelet-type subunits of PFK are unaffected. The paradox of mild erythrocytosis despite hemolysis reflects the decreased production of 2,3-DPG.
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000201:enzymology; D004163:Diphosphoglyceric Acids / Q000172:deficiency; D004912:Erythrocytes / Q000201:enzymology; D006461:Hemolysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D007962:Leukocytes / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics*; D009212:Myoglobinuria / Q000235:genetics*; D010732:Phosphofructokinase-1 / Q000172:deficiency*
chemical_list: D004163:Diphosphoglyceric Acids; D007527:Isoenzymes; D010732:Phosphofructokinase-1