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.

• Authors: S Vora, L Corash, W K Engel, S Durham, C Seaman, S Piomelli
• Journal: Blood (Blood) Vol. 55 Issue 4 Pg. 629-35 (Apr 1980) ISSN: 0006-4971 [Print] United States
• PMID: 6444532 (Publication Type: Case Reports, Journal Article)

Chemical References

• Diphosphoglyceric Acids
• Isoenzymes
• Phosphofructokinase-1

Topics

• Adult
• Blood Platelets (enzymology)
• Diphosphoglyceric Acids (deficiency)
• Erythrocytes (enzymology)
• Hemolysis
• Humans
• Isoenzymes (analysis)
• Leukocytes (enzymology)
• Liver (enzymology)
• Male
• Muscle Hypotonia (genetics)
• Myoglobinuria (genetics)
• Phosphofructokinase-1 (deficiency)