Evidence for transaldolase activity in the isolated heart supplied with [U-13C3]glycerol

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Abstract

Studies of glycerol metabolism in the heart have largely emphasized its role in triglyceride synthesis. However, glycerol may also be oxidized in the citric acid cycle, and glycogen synthesis from glycerol has been reported in the nonmammalian myocardium. The intent of this study was to test the hypothesis that glycerol may be metabolized to glycogen in mammalian heart. Isolated rat hearts were supplied with a mixture of substrates including glucose, lactate, pyruvate, octanoate, [U-13C3]glycerol, and 2H2O to probe various metabolic pathways including glycerol oxidation, glycolysis, the pentose phosphate pathway, and carbon sources of stored glycogen. NMR analysis confirmed that glycogen production from the level of the citric acid cycle did not occur and that the glycerol contribution to oxidation in the citric acid cycle was negligible in the presence of alternative substrates. Quite unexpectedly, 13C from [U-13C3]glycerol appeared in glycogen in carbon positions4-6ofglucosyl units but noneinpositions 1-3. The extent of [4, 5, 6-13C3]glucosyl unit enrichment in glycogen was enhanced by insulin but decreased by H2O2. Given that triose phosphate isomerase is generally assumed to fully equilibrate carbon tracers in the triose pool, the marked 13C asymmetry in glycogen can only be attributed to conversion of [U-13C3]glycerol to [U- 13C3]dihydroxyacetone phosphate and [U-13C 3]glyceraldehyde 3-phosphate followed by rearrangements in the nonoxidative branch of the pentose phosphate pathway involving transaldolase that places this 13C-enriched 3-carbon unit only in the bottom half of hexose phosphate molecules contributing to glycogen.

Original languageEnglish (US)
Pages (from-to)2914-2922
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number5
DOIs
StatePublished - Feb 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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