Energy Metabolism in Conformational Diseases

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Increasing evidence indicates that accumulation of unfolded/misfolded proteins results in protofibril and protein aggregate formation, inducing mitochondrial dysfunction and failure of synaptic, transport and other crucial physiological processes. Our knowledge on molecular defects of the energy metabolism in the pathogenesis of neurodegenerative diseases is scarce. One problem that investigators face is distinguishing primary from secondary events: is the impairment of energy production a consequence of the development of neurodegeneration, or it is an active contributor? Genomic and proteomic data provide useful information for understanding the structural and functional perturbations during the development of neurodegeneration, but the metabolomic alterations are much less disclosed. This paper reviews the direct and indirect role of the damage of energy metabolism, focusing on the metabolism of glucose as major energy source of the brain. Special attention is paid to the functional consequences of the associations of glycolytic enzymes with unfolded proteins that specifically determine the nature of the so-called "conformational diseases". This review shows that the available data are largely inconclusive for the evaluation of the pathomechanism of energy production defects in human brains of patients of conformational diseases at system level, and the genuine need for development of rational models (biosimulation) of neuropathological conversion of glucose to ATP via glycolysis and oxidative phosphorylation.

Original languageEnglish
Title of host publicationBiosimulation in Drug Development
PublisherWiley-VCH Verlag GmbH & Co. KGaA
Pages233-257
Number of pages25
ISBN (Print)9783527316991
DOIs
Publication statusPublished - Jul 11 2008

Fingerprint

Protein Unfolding
Energy Metabolism
Brain
Neurodegenerative diseases
Physiological Phenomena
Glucose
Defects
Metabolomics
Oxidative Phosphorylation
Glycolysis
Metabolism
Neurodegenerative Diseases
Proteomics
Proteins
Adenosine Triphosphate
Research Personnel
Enzymes
Protein Aggregates

Keywords

  • Biosimulation
  • Brain energy source
  • Conformational diseases
  • Drug metabolism
  • Energy metabolism
  • Glycolytic enzymes
  • Impair energy metabolism
  • Microcompartmentation
  • Neurodegenerative proteins
  • Post-translational modifications
  • Triosephosphate isomerase deficiency
  • Unfolded/misfolded proteins

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ovádi, J., & Orosz, F. (2008). Energy Metabolism in Conformational Diseases. In Biosimulation in Drug Development (pp. 233-257). Wiley-VCH Verlag GmbH & Co. KGaA. https://doi.org/10.1002/9783527622672.ch8

Energy Metabolism in Conformational Diseases. / Ovádi, J.; Orosz, F.

Biosimulation in Drug Development. Wiley-VCH Verlag GmbH & Co. KGaA, 2008. p. 233-257.

Research output: Chapter in Book/Report/Conference proceedingChapter

Ovádi, J & Orosz, F 2008, Energy Metabolism in Conformational Diseases. in Biosimulation in Drug Development. Wiley-VCH Verlag GmbH & Co. KGaA, pp. 233-257. https://doi.org/10.1002/9783527622672.ch8
Ovádi J, Orosz F. Energy Metabolism in Conformational Diseases. In Biosimulation in Drug Development. Wiley-VCH Verlag GmbH & Co. KGaA. 2008. p. 233-257 https://doi.org/10.1002/9783527622672.ch8
Ovádi, J. ; Orosz, F. / Energy Metabolism in Conformational Diseases. Biosimulation in Drug Development. Wiley-VCH Verlag GmbH & Co. KGaA, 2008. pp. 233-257
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