F G Hegardt

Summary

Affiliation: Universitat de Barcelona
Country: Spain

Publications

  1. pmc Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis
    F G Hegardt
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av Diagonal 643, 08028 Barcelona, Spain
    Biochem J 338:569-82. 1999
  2. ncbi request reprint Post-transcriptional regulation of rat carnitine octanoyltransferase
    F G Hegardt
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E 08028 Barcelona, Spain
    Biochem Soc Trans 29:316-20. 2001
  3. ncbi request reprint A two-base deletion in exon 6 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing the skipping of exons 5 and 6 determines 3-hydroxy-3-methylglutaric aciduria
    N Casals
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    J Lipid Res 38:2303-13. 1997
  4. ncbi request reprint Structural model of the catalytic core of carnitine palmitoyltransferase I and carnitine octanoyltransferase (COT): mutation of CPT I histidine 473 and alanine 381 and COT alanine 238 impairs the catalytic activity
    M Morillas
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E 08028 Barcelona, Spain
    J Biol Chem 276:45001-8. 2001
  5. ncbi request reprint Developmental changes in carnitine octanoyltransferase gene expression in intestine and liver of suckling rats
    A Miliar
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 385:283-9. 2001
  6. pmc Inhibition by etomoxir of rat liver carnitine octanoyltransferase is produced through the co-ordinate interaction with two histidine residues
    M Morillas
    Department of Biochemistry and Molecular Biology, University of Barcelona, School of Pharmacy, Diagonal 643, 08028 Barcelona, Spain
    Biochem J 351:495-502. 2000
  7. ncbi request reprint Low activity of mitochondrial HMG-CoA synthase in liver of starved piglets is due to low levels of protein despite high mRNA levels
    M J Barrero
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 385:364-71. 2001
  8. pmc Localization of an exonic splicing enhancer responsible for mammalian natural trans-splicing
    C Caudevilla
    Department of Biochemistry, School of Pharmacy, Diagonal 643, University of Barcelona, 08028 Barcelona, Spain
    Nucleic Acids Res 29:3108-15. 2001
  9. ncbi request reprint The expression of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A synthase in neonatal rat intestine and liver is under transcriptional control
    D Serra
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    Eur J Biochem 237:16-24. 1996
  10. ncbi request reprint Pig liver carnitine palmitoyltransferase I, with low Km for carnitine and high sensitivity to malonyl-CoA inhibition, is a natural chimera of rat liver and muscle enzymes
    C Nicot
    Department of Biochemistry and Molecular Biology, University of Barcelona, School of Pharmacy, 08028 Barcelona, Spain
    Biochemistry 40:2260-6. 2001

Collaborators

  • N Casals
  • R J Wanders
  • F Bosch
  • M Bach-Elias
  • M Ugarte
  • C Fillat
  • M Castro-Gago
  • S H Adams
  • B T Poll-The
  • M O Rolland
  • A Valencia
  • G Asins
  • D Serra
  • M Morillas
  • J Pie
  • G Arias
  • D Haro
  • C Mir
  • P Gomez-Puertas
  • N Zapater
  • P F Marrero
  • A Miliar
  • C Caudevilla
  • M J Barrero
  • C H Casale
  • C Nicot
  • B Puisac
  • C Rizzo
  • C Dionisi-Vici
  • R Aledo
  • F Deodato
  • E López-Viñas
  • J A Smeitink
  • C Buesa
  • C Codony
  • R Casaroli
  • A Graessmann
  • C S Alho
  • R Roca
  • J A Ortiz
  • G Woldegiorgis
  • G Plasencia
  • R Roman
  • J Clotet
  • J Arino
  • B Rubi
  • J M Garcia-Gonzalez
  • C Perez-Cerda
  • M Vidailhet
  • B Merinero
  • M Martínez-Pardo
  • J J García-Peñas
  • A Valera
  • J Lloberas
  • R Lama
  • B Leroux
  • J C Rodriguez
  • P Divry
  • A Barcelo
  • M Duran
  • C Mascaro
  • D Bellido
  • S Vilaro
  • T Royo
  • J Sabater
  • G Gil-Gomez
  • A Pujol
  • M Pelegrin

Detail Information

Publications24

  1. pmc Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis
    F G Hegardt
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av Diagonal 643, 08028 Barcelona, Spain
    Biochem J 338:569-82. 1999
    ....
  2. ncbi request reprint Post-transcriptional regulation of rat carnitine octanoyltransferase
    F G Hegardt
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E 08028 Barcelona, Spain
    Biochem Soc Trans 29:316-20. 2001
    ..These results indicate that the histidine residues His-131 and His-340 are the sites responsible for the interaction of these two inhibitors, which inhibit COT by interacting with the same sites...
  3. ncbi request reprint A two-base deletion in exon 6 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing the skipping of exons 5 and 6 determines 3-hydroxy-3-methylglutaric aciduria
    N Casals
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    J Lipid Res 38:2303-13. 1997
    ..We suggest that this deletion may affect the interaction between the small nuclear ribonucleoproteins (snRNPs) and exon 6, and that, as a result, the abnormal splicing of the pre-mRNA produces two different aberrant transcripts...
  4. ncbi request reprint Structural model of the catalytic core of carnitine palmitoyltransferase I and carnitine octanoyltransferase (COT): mutation of CPT I histidine 473 and alanine 381 and COT alanine 238 impairs the catalytic activity
    M Morillas
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E 08028 Barcelona, Spain
    J Biol Chem 276:45001-8. 2001
    ..The structural model explains the loss of activity reported for the CPT I mutations R451A, W452A, D454G, W391A, del R395, P479L, and L484P, all of which occur in or near the modeled catalytic domain...
  5. ncbi request reprint Developmental changes in carnitine octanoyltransferase gene expression in intestine and liver of suckling rats
    A Miliar
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 385:283-9. 2001
    ....
  6. pmc Inhibition by etomoxir of rat liver carnitine octanoyltransferase is produced through the co-ordinate interaction with two histidine residues
    M Morillas
    Department of Biochemistry and Molecular Biology, University of Barcelona, School of Pharmacy, Diagonal 643, 08028 Barcelona, Spain
    Biochem J 351:495-502. 2000
    ..Our data demonstrate that both etomoxir and malonyl-CoA inhibit COT by interacting with the same sites...
  7. ncbi request reprint Low activity of mitochondrial HMG-CoA synthase in liver of starved piglets is due to low levels of protein despite high mRNA levels
    M J Barrero
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 385:364-71. 2001
    ....
  8. pmc Localization of an exonic splicing enhancer responsible for mammalian natural trans-splicing
    C Caudevilla
    Department of Biochemistry, School of Pharmacy, Diagonal 643, University of Barcelona, 08028 Barcelona, Spain
    Nucleic Acids Res 29:3108-15. 2001
    ..Mutation of the GAAGAAG box to AAAAAAA abolished trans-splicing and decreased cis-splicing in vivo. We conclude that GAAGAAG is an exonic splicing enhancer that could induce natural trans-splicing in rat COT...
  9. ncbi request reprint The expression of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A synthase in neonatal rat intestine and liver is under transcriptional control
    D Serra
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    Eur J Biochem 237:16-24. 1996
    ....
  10. ncbi request reprint Pig liver carnitine palmitoyltransferase I, with low Km for carnitine and high sensitivity to malonyl-CoA inhibition, is a natural chimera of rat liver and muscle enzymes
    C Nicot
    Department of Biochemistry and Molecular Biology, University of Barcelona, School of Pharmacy, 08028 Barcelona, Spain
    Biochemistry 40:2260-6. 2001
    ..Therefore, pig L-CPTI behaves like a natural chimera of the L- and M-CPTI isotypes, which makes it a useful model to study the structure--function relationships of the CPTI enzymes...
  11. ncbi request reprint Two missense point mutations in different alleles in the 3-hydroxy-3-methylglutaryl coenzyme A lyase gene produce 3-hydroxy-3-methylglutaric aciduria in a French patient
    N Zapater
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 358:197-203. 1998
    ..Another sibling was free of the mutations. An enzymatic restriction analysis has been proposed to screen the occurrence of these two mutations in future patients...
  12. ncbi request reprint The effect of fasting/refeeding and insulin treatment on the expression of the regulatory genes of ketogenesis in intestine and liver of suckling rats
    G Arias
    Department of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 340:287-98. 1997
    ..The different effects of refeeding and insulin treatment on the expression of both genes, on the ketogenic rate, and on ketone body concentrations are discussed...
  13. ncbi request reprint Coordinated expression and activity of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase in the fat body of Blattella germanica (L.) during vitellogenesis
    N Casals
    Unit of Biochemistry, University of Barcelona, School of Pharmacy, Spain
    Insect Biochem Mol Biol 26:837-43. 1996
    ..Moreover, the pattern of mevalonate synthesis parallels that of vitellogenin production, suggesting a coordinate mechanism between the mevalonate pathway and the production of vitellogenin...
  14. ncbi request reprint A single-residue mutation, G203E, causes 3-hydroxy-3-methylglutaric aciduria by occluding the substrate channel in the 3D structural model of HMG-CoA lyase
    C Mir
    Department of Biochemistry and Molecular Biology, Faculty of Health Sciences, International University of Catalonia, C Josep Trueta s n, E 08190 Sant Cugat del Valles, Barcelona, Spain
    J Inherit Metab Dis 29:64-70. 2006
    ..Beta sheet six and beta sheet two are the two protein regions that accumulate most missense mutations, indicating their importance in enzyme functionality. A model for the mechanism of enzyme function is proposed...
  15. pmc Gene expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in a poorly ketogenic mammal: effect of starvation during the neonatal period of the piglet
    S H Adams
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Avda Diagonal, 643, 08028 Barcelona, Spain
    Biochem J 324:65-73. 1997
    ..These results indicate that post-transcriptional mechanism(s) and/or intrinsic differences in the encoded enzyme are responsible for the low activity of pig HMG-CoA synthase observed throughout development or after fasting...
  16. ncbi request reprint 3-Hydroxy-3-methylglutaryl coenzyme A synthase-1 of Blattella germanica has structural and functional features of an active retrogene
    N Casals
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E 08028, Barcelona, Spain
    Insect Biochem Mol Biol 31:425-33. 2001
    ..HMG-CoA synthase activity is not modified by either of these effectors, suggesting that the mevalonate pathway in this insect cell line is regulated by post-transcriptional mechanisms affecting HMG-CoA reductase but not HMG-CoA synthase...
  17. ncbi request reprint The effect of etomoxir on the mRNA levels of enzymes involved in ketogenesis and cholesterogenesis in rat liver
    G Asins
    Unit of Biochemistry, University of Barcelona, School of Pharmacy, Spain
    Biochem Pharmacol 47:1373-9. 1994
    ....
  18. ncbi request reprint Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids
    J C Rodriguez
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    J Biol Chem 269:18767-72. 1994
    ....
  19. ncbi request reprint The effect of dexamethasone treatment on the expression of the regulatory genes of ketogenesis in intestine and liver of suckling rats
    G Arias
    Department of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    Mol Cell Biochem 178:325-33. 1998
    ..Two day treatment with dexamethasone produced no change in mRNA or activity levels for CPT I in liver or intestine. While mRNA levels for mit. HMG-CoA synthase changed little, the enzyme activity is decreased in both tissues...
  20. ncbi request reprint A nonsense mutation in the exon 2 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing three mature mRNAs is the main cause of 3-hydroxy-3-methylglutaric aciduria in European Mediterranean patients
    C H Casale
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    Arch Biochem Biophys 349:129-37. 1998
    ..The mutation described here shows the highest incidence (> 37%) of total HL deficiencies reported...
  21. pmc Regulation of cytosolic 3-hydroxy-3-methylglutaryl-CoA synthase mRNA levels by L-tri-iodothyronine
    T Royo
    Unit of Biochemistry, University of Barcelona, School of Pharmacy, Spain
    Biochem J 289:557-60. 1993
    ..Administration of L-tri-iodothyronine (T3) resulted in a large increase in all three in hypophysectomized rats and in only a 2-fold increase (reaching the values of control rats) in thyroidectomized rats...
  22. ncbi request reprint Transcriptional regulation of mitochondrial HMG-CoA synthase in the control of ketogenesis
    F G Hegardt
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain
    Biochimie 80:803-6. 1998
    ..Other transcription factors such as chicken ovalbumin upstream promoter transcription factor (COUP-TF) and hepatocyte nuclear factor 4 (HNF-4) compete for the PPRE site, modulating the response of PPAR...
  23. ncbi request reprint Aberrantly spliced mRNAs of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene with a donor splice-site point mutation produce hereditary HL deficiency
    C Buesa
    Unit of Biochemistry, School of Pharmacy, University of Barcelona, Spain
    J Lipid Res 37:2420-32. 1996
    ..2%. The father, mother, and two brothers of the proband were heterozygous in the G-->C mutation in the +1 nucleotide of the intron considered, while the two alleles of another brother were free of the mutation...
  24. ncbi request reprint Overexpression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in transgenic mice causes hepatic hyperketogenesis
    A Valera
    Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain
    J Biol Chem 269:6267-70. 1994
    ..This animal model thus shows that the overexpression of mitochondrial HMG-CoA synthase causes ketone body overproduction, suggesting that this enzyme may be a regulatory step in liver ketogenesis...