The molecular mechanism of the inherited phosphofructokinase deficiency
associated with hemolysis and myopathy
S Vora, L Corash, WK Engel, S Durham, C Seaman and S Piomelli
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.
Volume 55,
Issue 4,
pp. 629-635,
04/01/1980
Copyright © 1980 by The American Society of Hematology
