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. 1987 Nov;80(5):1479–1485. doi: 10.1172/JCI113229

Characterization of the enzymatic defect in late-onset muscle phosphofructokinase deficiency. New subtype of glycogen storage disease type VII.

S Vora 1, S DiMauro 1, D Spear 1, D Harker 1, M J Danon 1
PMCID: PMC442407  PMID: 2960695

Abstract

Human phosphofructokinase (PFK) exists in tetrameric isozymic forms, at least in vitro. Muscle and liver contain homotetramers M4 and L4, respectively, whereas red cells contain five isozymes composed of M (muscle) and L (liver) type subunits, i.e., M4, M3L, M2L2, and ML3, and L4. Homozygous deficiency of muscle PFK results in the classic glycogen storage disease type VII characterized by exertional myopathy and hemolytic syndrome beginning in early childhood. The genetic lesion results in a total and partial loss of muscle and red cell PFK, respectively. Characteristically, the residual red cell PFK from the patients consists of isolated L4 isozyme; the M-containing hybrid isozymes are completely absent. In this study, we investigated an 80-yr-old man who presented with a 10-yr history of progressive weakness of the lower limbs as the only symptom. The residual red cell PFK showed the presence of a few M-containing isozymes in addition to the predominant L4 species, indicating that the genetic lesion is a "leaky" mutation of the gene coding for the M subunit. The presence of a small amount of enzyme activity in the muscle may account for the atypical myopathy in this patient.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaronson R. P., Frieden C. Rabbit muscle phosphofructokinase: studies on the polymerization. The behavior of the enzyme at pH 8, pH 6, and intermediate pH values. J Biol Chem. 1972 Dec 10;247(23):7502–7509. [PubMed] [Google Scholar]
  2. Beutler E., West C., Blume K. G. The removal of leukocytes and platelets from whole blood. J Lab Clin Med. 1976 Aug;88(2):328–333. [PubMed] [Google Scholar]
  3. Chance B., Eleff S., Bank W., Leigh J. S., Jr, Warnell R. 31P NMR studies of control of mitochondrial function in phosphofructokinase-deficient human skeletal muscle. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7714–7718. doi: 10.1073/pnas.79.24.7714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davidson M., Collins M., Byrne J., Vora S. Alterations in phosphofructokinase isoenzymes during early human development. Establishment of adult organ-specific patterns. Biochem J. 1983 Sep 15;214(3):703–710. doi: 10.1042/bj2140703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davidson M., Miranda A. F., Bender A. N., DiMauro S., Vora S. Muscle phosphofructokinase deficiency. Biochemical and immunological studies of phosphofructokinase isozymes in muscle culture. J Clin Invest. 1983 Aug;72(2):545–550. doi: 10.1172/JCI111002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Etiemble J., Simeon J., Buc H. A., Picat C., Boulard M., Boivin P. A liver-type mutation in a case of pronounced erythrocyte phosphofructokinase deficiency without clinical expression. Biochim Biophys Acta. 1983 Sep 13;759(3):236–242. doi: 10.1016/0304-4165(83)90318-5. [DOI] [PubMed] [Google Scholar]
  7. Hand S. C., Somero G. N. Urea and methylamine effects on rabbit muscle phosphofructokinase. Catalytic stability and aggregation state as a function of pH and temperature. J Biol Chem. 1982 Jan 25;257(2):734–741. [PubMed] [Google Scholar]
  8. Hays A. P., Hallett M., Delfs J., Morris J., Sotrel A., Shevchuk M. M., DiMauro S. Muscle phosphofructokinase deficiency: abnormal polysaccharide in a case of late-onset myopathy. Neurology. 1981 Sep;31(9):1077–1086. doi: 10.1212/wnl.31.9.1077. [DOI] [PubMed] [Google Scholar]
  9. Karadsheh N. S., Uyeda K., Oliver R. M. Studies on structure of human erythrocyte phosphofructokinase. J Biol Chem. 1977 May 25;252(10):3515–3524. [PubMed] [Google Scholar]
  10. Lad P. M., Hill D. E., Hammes G. G. Influence of allosteric ligands on the activity and aggregation of rabbit muscle phosphofructokinase. Biochemistry. 1973 Oct 23;12(22):4303–4309. doi: 10.1021/bi00746a001. [DOI] [PubMed] [Google Scholar]
  11. Layzer R. B., Rowland L. P., Ranney H. M. Muscle phosphofructokinase deficiency. Arch Neurol. 1967 Nov;17(5):512–523. doi: 10.1001/archneur.1967.00470290066009. [DOI] [PubMed] [Google Scholar]
  12. Leonard K. R., Walker I. O. The self-association of rabbit-muscle phosphofructokinase. Eur J Biochem. 1972 Apr 11;26(3):442–448. doi: 10.1111/j.1432-1033.1972.tb01785.x. [DOI] [PubMed] [Google Scholar]
  13. Pavelich M. J., Hammes G. G. Aggregation of rabbit muscle phosphofructokinase. Biochemistry. 1973 Mar 27;12(7):1408–1414. doi: 10.1021/bi00731a022. [DOI] [PubMed] [Google Scholar]
  14. Reinhart G. D., Lardy H. A. Rat liver phosphofructokinase: kinetic and physiological ramifications of the aggregation behavior. Biochemistry. 1980 Apr 1;19(7):1491–1495. doi: 10.1021/bi00548a036. [DOI] [PubMed] [Google Scholar]
  15. Reinhart G. D., Lardy H. A. Rat liver phosphofructokinase: use of fluorescence polarization to study aggregation at low protein concentration. Biochemistry. 1980 Apr 1;19(7):1484–1490. doi: 10.1021/bi00548a035. [DOI] [PubMed] [Google Scholar]
  16. Shimizu T., Kuwajima M., Kono N., Mineo I., Sumi S., Yonezawa T., Nonaka K., Tarui S. Kinetic properties of mutant enzymes in erythrocyte phosphofructokinase deficiency and erythrocyte pyruvate kinase deficiency. Med J Osaka Univ. 1983 Mar;33(3-4):49–58. [PubMed] [Google Scholar]
  17. TARUI S., OKUNO G., IKURA Y., TANAKA T., SUDA M., NISHIKAWA M. PHOSPHOFRUCTOKINASE DEFICIENCY IN SKELETAL MUSCLE. A NEW TYPE OF GLYCOGENOSIS. Biochem Biophys Res Commun. 1965 May 3;19:517–523. doi: 10.1016/0006-291x(65)90156-7. [DOI] [PubMed] [Google Scholar]
  18. Tani K., Fujii H., Miwa S., Imanaka F., Kuramoto A., Ishikawa H. Phosphofructokinase deficiency associated with congenital nonspherocytic hemolytic anemia and mild myopathy: biochemical and morphological studies on the muscle. Tohoku J Exp Med. 1983 Nov;141(3):287–293. doi: 10.1620/tjem.141.287. [DOI] [PubMed] [Google Scholar]
  19. Tani K., Fujii H., Takegawa S., Miwa S., Koyama W., Kanayama M., Imanaka A., Imanaka F., Kuramoto A. Two cases of phosphofructokinase deficiency associated with congenital hemolytic anemia found in Japan. Am J Hematol. 1983 Apr;14(2):165–174. doi: 10.1002/ajh.2830140208. [DOI] [PubMed] [Google Scholar]
  20. Tarui S., Kono N., Uyeda K. Purification and properties of rabbit erythrocyte phosphofructokinase. J Biol Chem. 1972 Feb 25;247(4):1138–1145. [PubMed] [Google Scholar]
  21. Vettore L., De Matteis M. C., Zampini P. A new density gradient system for the separation of human red blood cells. Am J Hematol. 1980;8(3):291–297. doi: 10.1002/ajh.2830080307. [DOI] [PubMed] [Google Scholar]
  22. Vora S., Davidson M., Seaman C., Miranda A. F., Noble N. A., Tanaka K. R., Frenkel E. P., Dimauro S. Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency. J Clin Invest. 1983 Dec;72(6):1995–2006. doi: 10.1172/JCI111164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Vora S., Durham S., de Martinville B., George D. L., Francke U. Assignment of the human gene for muscle-type phosphofructokinase (PFKM) to chromosome 1 (region cen leads to q32) using somatic cell hybrids and monoclonal anti-M antibody. Somatic Cell Genet. 1982 Jan;8(1):95–104. doi: 10.1007/BF01538653. [DOI] [PubMed] [Google Scholar]
  24. Vora S., Giger U., Turchen S., Harvey J. W. Characterization of the enzymatic lesion in inherited phosphofructokinase deficiency in the dog: an animal analogue of human glycogen storage disease type VII. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8109–8113. doi: 10.1073/pnas.82.23.8109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vora S., Hong F., Olender E. Isolation of a cDNA for human muscle 6-phosphofructokinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):615–621. doi: 10.1016/0006-291x(86)90037-9. [DOI] [PubMed] [Google Scholar]
  26. Vora S. Isozymes of human phosphofructokinase in blood cells and cultured cell lines: molecular and genetic evidence for a trigenic system. Blood. 1981 Apr;57(4):724–732. [PubMed] [Google Scholar]
  27. Vora S. Isozymes of phosphofructokinase. Isozymes Curr Top Biol Med Res. 1982;6:119–167. [PubMed] [Google Scholar]
  28. Vora S., Seaman C., Durham S., Piomelli S. Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system. Proc Natl Acad Sci U S A. 1980 Jan;77(1):62–66. doi: 10.1073/pnas.77.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vora S., Wims L. A., Durham S., Morrison S. L. Production and characterization of monoclonal antibodies to the subunits of human phosphofructokinase: new tools for the immunochemical and genetic analyses of isozymes. Blood. 1981 Oct;58(4):823–829. [PubMed] [Google Scholar]
  30. Wenzel K. -W., Zimmermann G., Gauer J., Diezel W., Liebe S., Hofmann E. Evidence for different oligomeric forms of human erythrocyte phosphofructokinase. FEBS Lett. 1972 Jan 1;19(4):285–289. doi: 10.1016/0014-5793(72)80061-9. [DOI] [PubMed] [Google Scholar]
  31. Zimmermann G., Wenzel K. W., Gauer J., Hofmann E. Studies on the association behaviour of human-erythrocyte phosphofructokinase. Eur J Biochem. 1973 Dec 17;40(2):501–505. doi: 10.1111/j.1432-1033.1973.tb03219.x. [DOI] [PubMed] [Google Scholar]

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