Propionate stimulates pyruvate oxidation in the presence of acetate

Colin Purmal, Blanka Kucejova, A. Dean Sherry, Shawn C. Burgess, Craig R. Malloy, Matthew E. Merritt

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Flux through pyruvate dehydrogenase (PDH) in the heart may be reduced by various forms of injury to the myocardium, or by oxidation of alternative substrates in normal heart tissue. It is important to distinguish these two mechanisms because imaging of flux through PDH based on the appearance of hyperpolarized (HP) [13C]bicarbonate derived from HP [1-13C]pyruvate has been proposed as a method for identifying viable myocardium. The efficacy of propionate for increasing PDH flux in the setting of PDH inhibition by an alternative substrate was studied using isotopomer analysis paired with exams using HP [1-13C]pyruvate. Hearts from C57/bl6 mice were supplied with acetate (2 mM) and glucose (8.25 mM). 13C NMR spectra were acquired in a cryogenically cooled probe at 14.1 Tesla. After addition of hyperpolarized [1-13C]pyruvate, 13C NMR signals from lactate, alanine, malate, and aspartate were easily detected, in addition to small signals from bicarbonate and CO2. The addition of propionate (2 mM) increased appearance of HP [13C]bicarbonate >30-fold without change in O2consumption. Isotopomer analysis of extracts from the freeze-clamped hearts indicated that acetate was the preferred substrate for energy production, glucose contribution to energy production was minimal, and anaplerosis was stimulated in the presence of propionate. Under conditions where production of acetyl-CoA is dominated by the availability of an alternative substrate, acetate, propionate markedly stimulated PDH flux as detected by the appearance of hyperpolarized [13C]bicarbonate from metabolism of hyperpolarized [1-13C]pyruvate.

Original languageEnglish (US)
Pages (from-to)H1134-H1141
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number8
DOIs
StatePublished - Oct 15 2014

Keywords

  • Glucose
  • Hyperpolarization
  • Isotopomer analysis
  • Propionate
  • Pyruvate
  • Substrate selection

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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