Age-related compensatory activation of pyruvate dehydrogenase complex in rat heart

Régis Moreau, Shi Hua D. Heath, Catalin E. Doneanu, Robert A. Harris, Tory M. Hagen

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16 Scopus citations

Abstract

Mitochondrial uptake and β-oxidation of long-chain fatty acids are markedly impaired in the aging rat heart. While these alterations would be expected to adversely affect overall pyridine nucleotides, NADH levels do not change significantly with age. This conundrum suggests that specific compensatory mechanisms occur in the aging heart. The comparison of cardiac pyruvate dehydrogenase complex (PDC) kinetics in 4- and 24- to 28-month-old F344 rats revealed a 60% significant increase in V max with no change in PDC expression, and a 1.6-fold decrease in the Michaelis constant (K m) in old compared to young rats. The observed kinetic adjustments were selective to PDC, as neither the V max nor K m of citrate synthase changed with age. PDC kinase-4 mRNA levels decreased by 57% in old vs young rat hearts and correlated with a 45% decrease in PDC phosphorylation. We conclude that PDC from old rat hearts catabolizes pyruvate more efficiently due to an adaptive change in phosphorylation.

Original languageEnglish (US)
Pages (from-to)48-58
Number of pages11
JournalBiochemical and Biophysical Research Communications
Volume325
Issue number1
DOIs
StatePublished - Dec 3 2004

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Keywords

  • Aging
  • ATP
  • Energetics
  • Heart
  • Kinetics
  • Mitochondria
  • Myocardium
  • NADH
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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