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Long-term regulation and promoter analysis of mammalian pyruvate dehydrogenase complex

  • Chapter
Alpha-Keto Acid Dehydrogenase Complexes

Part of the book series: MCBU Molecular and Cell Biology Updates ((MCBU))

Abstract

The mammalian pyruvate dehydrogenase complex (PDC) plays a key role in the irreversible decarboxylation of pyruvate derived from glucose and amino acids to form acetyl-CoA in the mitochondria. Acetyl-CoA is then utilized for either energy production by the tricarboxylic acid cycle or energy storage by the lipogenic pathway. This enzyme complex contains multiple copies of three catalytic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetytransferase (E2) and dihydrolipoamide dehydrogenase (E3), two regulatory components (E1-kinase, phospho-E1 phosphatase) and one non-catalytic protein X (also referred to as E3-binding protein) (for review see: Reed, 1974; Patel and Roche, 1990; Behal et al., 1993).

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References

  • Bagley, P.R., Tucker, S.P., Nolan, C., Lindsey, J.G., Davies, A., Baldwin, S.A., Cremer, J.E. and Cunningham, VJ. (1989) Anatomical mapping of glucose transporter protein and pyruvate dehydrogenase in rat brain: an immunogold study. Brain Res. 409: 214–224.

    Article  Google Scholar 

  • Benelli, C., Caron, M., de Galle, B., Fouque, F., Cherqui, G. and Clot, J.-P. (1994) Evidence for a role of protein kinase C in the activation of the pyruvate dehydrogenase complex by insulin in Zajdela hepatoma cells. Metabolism 43: 1030–1034.

    Article  PubMed  CAS  Google Scholar 

  • Behal, R.H., Browning, K.S., Hall, B.T. and Reed, L.J. (1989) Cloning and nucleotide sequence of the gene for protein X from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 86: 8732–8736.

    Article  PubMed  CAS  Google Scholar 

  • Behal, R.H., Buxton, D.B., Robertson, J.G. and Olson, M.S. (1993) Regulation of the pyruvate dehydrogenase multienzyme complex. Ann. Rev. Nutr. 13: 497–520.

    Article  CAS  Google Scholar 

  • Begum, N., Tepperman, H.M. and Tepperman, J. (1983) Effects of high fat and high carbohydrate diets on liver pyruvate dehydrogenase and its activation by a chemical mediator released from insulin-treated liver particulate fraction: Effect of neuraminidase treatment on the chemical mediator activity. Endocrinology 112: 50–59.

    Article  PubMed  CAS  Google Scholar 

  • Brown, R.M., Dahl, H.–H. M. and Brown, G.K. (1989) X chromosome location of the functional gene for the E1α subunit of the human pyruvate dehydrogenase complex. Genomics 4: 174–181.

    Article  PubMed  CAS  Google Scholar 

  • Butterworth, R.F. and Giguere, J.F. (1984) Pyruvate dehydrogenase activity in regions of the rat brain during postnatal development. J. Neurochem. 43: 280–282.

    Article  PubMed  CAS  Google Scholar 

  • Carothers, D.J., Pons, G. and Patel, M.S. (1988) Induction of dihydrolipoamide dehydrogenase in 3T3-L1 cells during differentiation. Biochem. J. 214: 177–181.

    Google Scholar 

  • Chang, M., Naik, S., Johanning, G.L., Ho, L. and Patel, M.S. (1993) Multiple protein-binding domains and functional cis-elements in the 5’-flanking region of the human pyruvate dehydrogenase α-subunit gene. Biochemistry 32: 4263–4269.

    Article  PubMed  CAS  Google Scholar 

  • Chicco, A., Gutman, R., Basilico, M. and Lombardo, Y. (1986) Pyruvate dehydrogenase (PDH) activity in heart, liver and adipose tissue of rats fed a sucrose-rich diet. Nutr. Rep. Intl. 33: 465–475.

    CAS  Google Scholar 

  • Chitra, C.I., Cuezva, J.M. and Patel, M.S. (1985) Changes in the activity of active pyruvate dehydrogenase complex in the newborn of normal and diabetic rats. Diabetologia 28: 148–152.

    PubMed  CAS  Google Scholar 

  • Coore, H.G. and Field, B. (1974) Properties of pyruvate dehydrogenase of rat mammary tissue and its changes during pregnancy, lactation, and weaning. Biochem. J. 142: 87–95.

    PubMed  CAS  Google Scholar 

  • Coppel, R.L., McNeilage, L.J., Surh, C.D., Van De Water, Spithill, T., Whittingham, S. and Gershwin, M.E. (1988) Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase. Proc. Natl. Acad. Sci. USA 85: 7317–7321.

    Article  PubMed  CAS  Google Scholar 

  • Cremer, J.E. and Teal, H.M. (1974) The activity of pyruvate dehydrogenase in rat brain during postnatal development. FEBS Lett. 39: 17–20.

    Article  PubMed  CAS  Google Scholar 

  • Cross, J.H., Connelly, A., Gadian, D.G., Kendall, B.E., Brown, G.K., Brown, R.M. and Leonard, J.V. (1994) Clinical diversity of pyruvate dehydrogenase deficiency. Pediat. Neurol. 10: 276–283.

    Article  PubMed  CAS  Google Scholar 

  • Cullingford, T.E., Clark, J.B. and Philips, I.R. (1993) Characterization of cDNAs encoding the rat testis-specific E1α subunit of the pyruvate dehydrogenase complex: comparison of expression of the corresponding mRNA with that of the somatic E1α subunit. Biochim. Biophys. Acta 1216: 149–153.

    PubMed  CAS  Google Scholar 

  • Cullingford, T.E., Clark, J.B. and Phillips, I.R. (1994) The pyruvate dehydrogenase complex: cloning of the rat somatic Elα subunit and its coordinate expression with the mRNA for the E1β, and E2 and E3 catalytic subunits in developing rat brain. J. Neurochem. 62: 1682–1690.

    Article  PubMed  CAS  Google Scholar 

  • Dahl, H.-H.M., Hunt, S.M., Hutchison, W.M. and Brown, G.K. (1987) The human pyruvate dehydrogenase complex: Isolation of cDNA clones for the E1α subunit, sequence analysis and characterization of the mRNA. J. Biol Chem. 262: 7398–7405.

    PubMed  CAS  Google Scholar 

  • Dahl, H.-H.M., Brown, R.M., Hutchinson, W.M., Maragos, C. and Brown, G.K. (1990) A testis-specific form of the human pyruvate dehydrogenase E1α subunit is coded for by an intronless gene on chromosome 4. Genomics 8: 225–232.

    Article  PubMed  CAS  Google Scholar 

  • Da Silva, L.A., De Marcucci, O.L. and Carmona, A. (1992) Adaptive changes in total pyruvate dehydrogenase activity in lipogenic tissues of rats fed high-sucrose or high-fat diets. Comp. Biochem. Physiol. 103A: 407–411.

    Google Scholar 

  • Da Silva, L.A., De Marcucci, O.L. and Kuhnle, Z.R. (1993) Dietary polyunsaturated fats suppress the high-sucrose induced increase of rat liver pyruvate dehydrogenase levels. Biochim. Biophys. Acta 1169: 126–134.

    PubMed  CAS  Google Scholar 

  • Farese, R.V., Standaert, M.L., Barnes, D.E., Davis, J.S. and Pollet, R.J. (1985) Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes. Endocrinology 116: 2650–2655.

    Article  PubMed  CAS  Google Scholar 

  • Feigenbaum, A.S. and Robinson, B.H. (1993) The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Genomics 17: 376–381.

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald, J., Wilcox, S.A., Marshall Graves, J.A. and Dahl, H.-H.M. (1993) A eutherian X-linked gene, PDHA1, is autosomal in marsupials: A model for the evolution of a second, testis-specific variant in eutherian mammals. Genomics 18: 636–642.

    Article  PubMed  CAS  Google Scholar 

  • Goodison, S., Kenna, S. and Ashcroft, S.J.H. (1992) Control of insulin gene expression by glucose. Biochem. J. 285: 563–568.

    PubMed  CAS  Google Scholar 

  • Goto, M., Masamune, Y. and Nakanishi, Y. (1993) A factor stimulating transcription of the testis-specific Pgk-2 gene recognizes a sequence similar to the binding site for a transcription inhibitor of the somatic-type Pgk-1 gene. Nucleic Acids Res. 21: 209–214.

    Article  PubMed  CAS  Google Scholar 

  • Gottschalk, W.K. (1991) The pathway mediating insulin’s effect on pyruvate dehydrogenase bypasses the insulin receptor tyrosine kinase. J. Biol Chem. 266: 8814–8819.

    PubMed  CAS  Google Scholar 

  • Hu, C.-W.C., Utter, M.F. and Patel, M.S. (1983) Induction of pyruvate dehydrogenase in 3T3-L1 cells during differentiation. J. Biol Chem. 258: 2315–2320.

    PubMed  CAS  Google Scholar 

  • Huh, T.L., Huh, J.W., Veech, R.L. and Song, B.J. (1991) Coordinate, pretranslational expression of pyruvate dehydrogenase complex during adipocyte differentiation. FASEB J. 5: A1200.

    Google Scholar 

  • Iannello, R.C., Kola, I. and Dahl, H.-H. M. (1993) Temporal and tissue-specific interactions involving novel transcriptional factors and the proximal promoter of the mouse Pdha-2 gene. J. Biol Chem. 268: 22581–22590.

    PubMed  CAS  Google Scholar 

  • Johanning, G.L., Morris, J.I., Madhusudhan, K.T., Samols, D. and Patel, M.S. (1992) Characterization of the transcriptional regulatory region of the human dihydrolipoamide dehydrogenase gene. Proc. Natl Acad. Sci. USA 89: 10964–10968.

    Article  PubMed  CAS  Google Scholar 

  • Kerbey, A.L. and Randle, P.J. (1982) Pyruvate dehydrogenase kinase/activator in rat heart mitochondria. Assay, effect of starvation and effect of protein synthesis inhibitors in starvation. Biochem. J. 206: 103–111.

    PubMed  CAS  Google Scholar 

  • Knowles, S.E. and Ballard, F.J. (1974) Pyruvate dehydrogenase activity in rat liver during development. Biol Neonate 24: 41–48.

    Article  PubMed  CAS  Google Scholar 

  • Koike, K., Urata, Y. and Koike, M. (1990) Molecular cloning and characterization of human pyruvate dehydrogenase β-subunit gene. Proc. Natl Acad. Sci. USA 87: 5594–5597.

    Article  PubMed  CAS  Google Scholar 

  • Lilley, K., Zhang, C., Villar-Palasi, C., Larner, J. and Huang, L. (1992) Insulin mediator stimulation of pyruvate dehydrogenase phosphatases. Arch. Biochem. Biophys. 296: 170–174.

    Article  PubMed  CAS  Google Scholar 

  • Malloch, G.D.A., Munday, L.A., Olson, M.S. and Clark, J.B. (1986) Comparative development of pyruvate dehydrogenase complex and citrate synthase in rat brain mitochondria. Biochem. J. 238: 729–736.

    PubMed  CAS  Google Scholar 

  • MacDonald, M.J., Kaysen, J.H., Moran, S.M. and Pomije, C.E. (1991) Pyruvate dehydrogenase and pyruvate carboxylase: Sites of pretranslational regulation by glucose of glucose-induced insulin release in pancreatic islets. J. Biol Chem. 266: 22392–22397.

    PubMed  CAS  Google Scholar 

  • Madhusudhan, K.T., Naik, S. and Patel, M.S. (1995) Characterization of the promoter regulatory region of the human pyruvate dehydrogenase p gene. Biochemistry 34: 1288–1294.

    Article  PubMed  CAS  Google Scholar 

  • Maragos, C., Hutchison, W.M., Hayasaka, K., Brown, G.K. and Dahl, H.-H.M. (1989) Structural organization of the gene for the E1α subunit of the human pyruvate dehydrogenase complex. J. Biol Chem. 264: 12294–12298.

    PubMed  CAS  Google Scholar 

  • Matuda, S., Nakano, K., Ohta, S., Saheki, T., Kawanishi, Y. and Miyata, T. (1991) The α-ketoacid dehydrogenase complexes. Sequence similarities of rat pyruvate dehydrogenase with Escherichia coli and Azotobacter vinelandii α-ketoglutarate dehydrogenase. Biochim. Biophys. Acta 1089: 1–7.

    PubMed  CAS  Google Scholar 

  • Matuda, S., Nakano, K., Ohta, S., Shimura, M., Yamanaka, T., Nakagawa, S., Titani, K. and Miyata, T. (1992) Molecular cloning of the dihydrolipoamide acetyltransferase of the rat pyruvate dehydrogenase complex: sequence comparison and evolutionary relationship to other dihydrolipoamide acyltransferases. Biochim. Biophys. Acta 1131: 114–118.

    PubMed  CAS  Google Scholar 

  • Milner, T.A., Aoki, C. Rex Sheu, K.-F., Blass, J.P. and Pickel, V.M. (1987) Light microscopic immunocytochemical localization of pyruvate dehydrogenase complex in rat brain: topographical distribution and relation to cholinergic and catecholaminergic nuclei. J. Neurochem. 7: 3171–3190.

    CAS  Google Scholar 

  • Moehario, L.H., Smooker, P.M., Devenish, R.J., Mackay, I.R., Gershwin, M.E.and Marzuki, S. (1990) Nucleotide sequence of a cDNA encoding the lipoate acetyltransferase (E2) of human heart pyruvate dehydrogenase complex differs from that of human placenta. Biochem. Int. 20: 411–422.

    Google Scholar 

  • Orfali, K.A., Fryer, L.G.D., Holness, M.J. and Sugden, M.C. (1993) Long-term regulation of pyruvate dehydrogenase kinase by high-fat feeding. Experiments in vivo and in cultured cardiomyocytes. FEBS Lett. 336: 501–505.

    Article  PubMed  CAS  Google Scholar 

  • Patel, M.S. and Roche, T.E. (1990) Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J. 4: 3224–3233.

    PubMed  CAS  Google Scholar 

  • Patel, M.S. and Harris, R.A. (1995) α-Keto acid dehydrogenase complexes: gene regulation and genetic defects. FASEB J. 9: 1164–1172.

    PubMed  CAS  Google Scholar 

  • Pons, G., Raefsky-Estrin, C., Carothers, D.J., Pepin, R.A., Javed, A.A., Jesse, B.W., Ganapathi, M.K., Samols, D. and Patel, M.S. (1988) Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human α-ketoacid dehydrogenase complexes. Proc. Natl. Acad. Sci. USA 85: 1422–1426.

    Article  PubMed  CAS  Google Scholar 

  • Reed, L.J. (1974) Multienzyme complexes. Acc. Chem. Res. 7: 40–46.

    Article  CAS  Google Scholar 

  • Robinson, B.H., MacMillan, H., Petrova-Benedict, R. and Sherwood, W.G. (1987) Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex. J. Pediatr. III: 525–533.

    Google Scholar 

  • Roche, T.E. and Patel, M.S. (1989) Alpha-keto acid dehydrogenase complexes: organization, regulation and biomedical ramifications. Ann. N.Y. Acad. Sci. 573: 1–474.

    Article  Google Scholar 

  • Romero, G. and Larner, J. (1993) Insulin mediators and the mechanism of insulin action. Adv. Pharm. 24: 21–50.

    Article  CAS  Google Scholar 

  • Saffer, J.D., Jackson, S.P. and Annarella, M.B. (1991) Developmental expression of Spl in the mouse. Mol. Cell. Biol. 11: 2189–2199.

    PubMed  CAS  Google Scholar 

  • Scherer, S.W., Otulakowski, G., Robinson, B.H. and Tsui, L.-C. (1991) Localization of the human dihydrolipoamide dehydrogenase gene (DLD) to 7q31-q32. Cytogenet. Cell Genet. 56: 176–177.

    Article  PubMed  CAS  Google Scholar 

  • Serrano, E., Luis, A.M., Encabo, P., Alconada, A., Ho, L., Patel, M.S. and Cuezva, J.M. (1989) Rapid postnatal induction of the pyruvate dehydrogenase complex in the rat liver mitochondria. Ann. N. Y. Acad. Sci. 573: 412–415.

    Article  Google Scholar 

  • Sperl, W., Sengers, R.C.A., Trijbels, J.M.F., Ruitenbeek, W., De Graaf, R., Terlaak, H., Van Lith, T., Kerkhoff, C. and Janssen, A. (1992) Postnatal development of pyruvate dehydrogenase oxidation in quadriceps muscle of rat. Biol. Neonate 61: 188–200.

    Article  PubMed  CAS  Google Scholar 

  • Sugden, M.C. and Holness, M.J. (1994) Interactive regulation of the pyruvate dehydrogenase complex and the carnitine palmitoyltransferase system. FASEB J. 8: 54–61.

    PubMed  CAS  Google Scholar 

  • Takakubo, F. and Dahl, H.-H.M. (1994) Analysis of pyruvate dehydrogenase expression in embryonic mouse brain: localization and developmental regulation. Dev. Brain Res. 7: 63–75.

    Article  Google Scholar 

  • Thekkumkara, T.J., Ho, L., Wexler, I.D., Pons, G., Leu, T.C. and Patel, M.S. (1988) Nucleotide sequence of a cDNA for the dihydrolipoamide acetyltransferase component of human pyruvate dehydrogenase complex. FEBS Lett. 240: 45–48.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, K.S. and Towle, H.C. (1991) Localization of the carbohydrate response element of the rat L-type pyruvate kinase gene. J. Biol. Chem. 266: 8679–8682.

    PubMed  CAS  Google Scholar 

  • Weinberg, M.B. and Utter, M.F. (1979) Effect of thyroid hormone on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase. J. Biol. Chem. 254: 9492–9499.

    PubMed  CAS  Google Scholar 

  • Wieland, O.H. (1983) The mammalian pyruvate dehydrogenase complex: structure and regulation. Rev. Physiol. Biochem. Pharmacol. 96: 123–169.

    Article  PubMed  CAS  Google Scholar 

  • Wieland, O.H., Urumow, T. and Drexler, P. (1989) Insulin, phospholipase, and the activation of the pyruvate dehydrogenase complex: an enigma. Ann. N.Y. Acad. Sci. 573: 274–284.

    Article  PubMed  CAS  Google Scholar 

  • Wilbur, D.O. and Patel, M.S. (1974) Development of mitochondrial pyruvate metabolism in rat brain. J. Neurochem. 22: 709–715.

    Article  PubMed  CAS  Google Scholar 

  • Zawel, L. and Reinberg, D. (1993) Initiation of transcription by RNA polymerase II: a multi-step process. Prog. Nucl. Acid Res. Mol. Biol. 44: 67–108.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    M. S. Patel & R. Dey

  2. Departments of Biochemistry and Genetics, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA

    S. Naik & M. Johnson

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  1. M. S. Patel
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  2. S. Naik
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  3. M. Johnson
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Editors and Affiliations

  1. Department of Biochemistry School of Medicine and Biomedical Sciences, State University of New York, 140 Farber Hall 3435 Main Street, 14214, Buffalo, New York, USA

    Mulchand S. Patel

  2. Department of Biochemistry, Kansas State University, 104 Willard Hall, 66506, Manhattan, KS, USA

    Thomas E. Roche

  3. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, 46202, Indianapolis, IN, USA

    Robert A. Harris

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© 1996 Birkhäuser Verlag Basel/Switzerland

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Patel, M.S., Naik, S., Johnson, M., Dey, R. (1996). Long-term regulation and promoter analysis of mammalian pyruvate dehydrogenase complex. In: Patel, M.S., Roche, T.E., Harris, R.A. (eds) Alpha-Keto Acid Dehydrogenase Complexes. MCBU Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-8981-0_15

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  • DOI: https://doi.org/10.1007/978-3-0348-8981-0_15

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-9853-9

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