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Isolation, characterization, and mapping of gene encoding dihydrolipoyl succinyltransferase (E2k) of humanα-ketoglutarate dehydrogenase complex

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Somatic Cell and Molecular Genetics

Abstract

We have isolated and sequenced cDNAs representing the full-length (2987-bp) gene for dihydrolipoyl succinyltransferase (E2k component) of the humanα-ketoglutarate dehydrogenase comple (KGDHC) from a human fetal brain cDNA library. The E2k cDNA was mapped to human chromosome 14 using a somatic cell hybrid panel, and more precisely to band 14q24.3 by in situ hybridization. This cDNA also cross-hybridized to an apparent E2k pseudogene on chromosome 1p31. Northern analysis revealed the E2k gene to be ubiquitously expressed in peripheral tissues and brain. Interestingly, chromosome 14q24.3 has recently been reported to contain gene defects for an early-onset form of familial Alzheimer's disease and for Machado-Joseph disease. Future studies will be necessary to determine whether the E2k gene plays a role in either of these two disorders.

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Literature Cited

  1. Nakano, K., Sadayuki, M., yamanaka, T., Tsubouchi, H., Nakagawa, S., Titani, K., Ohta, S., and Miyata, T. (1991). Purification and molecular cloning of succinyltransferase of the ratα-ketoglutarate dehydrogenase complex.J. Biol. Chem. 266:19013–19017.

    Google Scholar 

  2. Nobukuni, Y., Mitsobuchi, H., Endo, F., and Matsuda, I. (1989). Complete primary structure of the transacylase (E2b) subunit of the human branched chain alpha-keto acid dehydrogenase complex.Biochem. Biophys. Res. Commun. 161: 1035–1041.

    Google Scholar 

  3. Cai, X., Szabo, P., Ali, G., Tanzi, R.E., and Blass, J.P., (1994). A pseudogene of dihydrolipoyl succinyltransferase (E2k) found by PCR amplification and direct sequencing of rodent-human cell hybrid DNAs (In press).

  4. Schellenberg, G.D., Bird, T.D., Wijsman, E.M., Orr, H.T., Anderson, L., Nemens, E., White, J.A., Bonnycastle, L., Weber, J.L., Alonso, M.E., Potter, H., Heston, L.L., and Martin, G. (1992). Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14.Science 258:668–671.

    Google Scholar 

  5. St. George-Hyslop, P.H., Haines, J., Rogaev, E., Mortilla, M., Vaula, G., Pericak-Vance, M., Foncin, J.-F., Montesi, M., Bruni, A., Sorbi, S., Rainero, I., Pinessi, L., Pollen, D., Polinsky, R., Nee, L., Kennedy, J., Macciardi, F., Rogaeva, E., Liang, Y., Alexandrova, N., Lukiw, W., Schlumpf, K., Tanzi, R., Tsuda, T., Farrer, L., Cantu, J-M., Duara, R., Amaducci, L., Bergamini, L., Gusella, J., Roses, A., and Crapper-McLachlan, D. (1992). Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.Nature Genet. 2:330–334.

    Google Scholar 

  6. Van Broeckhoven, C., Backhovens, H., Cruts, M., De Winter, G., Bruyland, M., Cras, P., Martin, J.-J. (1992). Mapping of a gene predisposing to earlyonset Alzheimer's disease to chromosome 14q24.3.Nature Genet.,2:334–339.

    Google Scholar 

  7. Mullan, M., Houlden, H., Windelspecht, M., Fidani, L., Lombardi, C., Diaz, P., Rossor, M., Crook, R., Hardy, J., and Crawford, F. (1992). A locus for familial Alzheimer's disease on the long arm of chromosome 14, proximal to the alpha-1-antichymotrypsin gene.Nature Genet. 2:340–342.

    Google Scholar 

  8. Takiyama, Y., Nishizawa, M., Tanaka, H., Kawashima, S., Sakamoto, H., Karube, Y., Shimazaki, H., Soutome, M., Endo, K., Ohta, S., Kagawa, Y., Kanazawa, I., Mizuno, Y., Yoshida, M., Yuasa, T., Horikawa, Y., Oyanagi, K., Nagai, ?., Kondo, T., Inuzuka, T., Onodera, O., and Tsuji, S. (1993).Nature Genet.,4:300–304.

    Google Scholar 

  9. Blass, J.P., and Gibson, G.E. (1991). The role of oxidative abnormalities in the pathophysiology of Alzheimer's disease.Rev. Neurol. (Paris) 147:513–525.

    Google Scholar 

  10. Blass, J.P., and Sheu, K.-F.R. (1990). energy metabolism in disorders of the nervous system.Rev. Neurol. (Paris) 144:543–563.

    Google Scholar 

  11. Blass, J.P. (1994). Pathophysiology of the Alzheimer syndrome.Neurology 43:Suppl. 4, 535–538.

    Google Scholar 

  12. Blass, J.P. (1994). Metabolic alterations common to neural and non-neural cells in Alzheimer's disease.Hippocampus 3:45–54.

    Google Scholar 

  13. Perry, E.K., Perry, R.H., Tomlinson, B.E., et al. (1990). Coenzyme-A acetylating enzymes in Alzheimer's disease: Possible cholinergic “compartment” of pyruvate dehydrogenase.Neurosci. Lett. 18:105–110.

    Google Scholar 

  14. Sheu, K.-F.R., Kim, Y.-T., Blass, J.P., and Weksler, M.E. (1985). An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain.Ann. Neurol. 17:444–449.

    Google Scholar 

  15. Yates, C.M., Butterworth, J., Tennant, M.C., and Gordon, A. (1990). Enzyme activities in relation to pH and lactate in post-mortem brain in Alzheimertype and other dementias.J. Neurochem.,55:1624–1630.

    Google Scholar 

  16. Gibson, G.E., Sheu, K.-F.R., Blass, J.P., et al. 1988). Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease.Arch. Neurol. 45:836–840.

    Google Scholar 

  17. Butterworth, R.F., and Besnard, A.-M. (1990). Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer's disease.Metabol. Brain Dis.,5:179–184.

    Google Scholar 

  18. Mastrogiacomo, F., Bergeron, C., and Kish, S.J. (1994). Brainα-ketoglutarate dehydrogenase activity in Alzheimer's disease.J. Neurochem. (in press).

  19. Kalaria, R.N., and Harik, S.I. (1992). Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer's disease.Ann. Neurol. 22:583–586.

    Google Scholar 

  20. Kish, S.J., Bergeron, C., Rajput, A., et al. (1992). Brain cytochrome oxidase in Alzheimer's disease.J. Neurochem. 59:776–779.

    Google Scholar 

  21. Brown, G.G., Levine, S.R., Gorell, J.M., et al. (1989). In vivo31P-NMR profiles of Alzheimer's disease and multiple subcortical infarct dementia.Neurology 39:1423–1427.

    Google Scholar 

  22. Jagust, W.J., Friedland, R.P., Budinger, T.F., et al. (1988). Longitudinal studies of regional cerebral metabolism in Alzheimer's disease.Neurology 38:900–912.

    Google Scholar 

  23. Hoyer, S. (1991) Abnormalities of glucose metabolism in Alzheimer's disease.Ann. N.Y. Acad. Sci. 640:53–58.

    Google Scholar 

  24. Sims, N.R., Bowen, D.M., Neary, D., and Davison, A.N. (1983). Metabolic processes in Alzheimer's disease: Adenine nucleotide content and production of14CO2 from [U-14C]glucose in vitro in human neocortex.J. Neurochem. 41:1329–1334.

    Google Scholar 

  25. Sim, N.R., Finegan, J.M., Blass, J.P., et al. (1987). Mitochondrial function in brain tissue in primary degenerative dementia.Brain Res. 436:30–38.

    Google Scholar 

  26. Sheu, K.-F.R., Cooper, A.J.L., Koike, K., Koike, M., Lindsay, J.G., and Blass, J.P. (1994). Abnormality of theα-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer's disease.Ann. Neurol. 35:312–318.

    Google Scholar 

  27. Gerhard, D.S., Kawasaki, E.S., Bancroft, F.C., and Szabo, P. (1981). Localization of a unique gene by direct hybridization in situ.Proc. Natl. Acad. Sci. U.S.A. 78:3755–3759.

    Google Scholar 

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Authors and Affiliations

  1. Burke Medical Research Institute, Cornell University Medical College, 10605, White Plains, New York

    Ghazala Ali, Xingang Cai, Kwan-Fu R. Sheu & John P. Blass

  2. Laboratory of Genetics and Aging, Massachusetts General Hospital, 02129, Charlestown, Massachusetts

    Wilma Wasco, Sandra M. Gaston & Rudolph E. Tanzi

  3. Geriatrics, Biochemistry, Cornell University Medical College, 10021, New York, New York

    Paul Szabo

  4. Molecular Neurogenetics Unit, Massachusetts General Hospital, 02129, Charlestown, Massachusetts

    Arthur J. L. Cooper & James F. Gusella

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  1. Ghazala Ali
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  2. Wilma Wasco
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  3. Xingang Cai
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  4. Paul Szabo
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  5. Kwan-Fu R. Sheu
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  9. Rudolph E. Tanzi
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  10. John P. Blass
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Ali, G., Wasco, W., Cai, X. et al. Isolation, characterization, and mapping of gene encoding dihydrolipoyl succinyltransferase (E2k) of humanα-ketoglutarate dehydrogenase complex. Somat Cell Mol Genet 20, 99–105 (1994). https://doi.org/10.1007/BF02290679

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  • DOI: https://doi.org/10.1007/BF02290679

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