Evidence for Transaldolase Activity in the Isolated Heart Supplied with [U-13C3]Glycerol |
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Authors: | Eunsook S Jin A Dean Sherry Craig R Malloy |
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Institution: | From the ‡Advanced Imaging Research Center.;§Department of Internal Medicine, and ;¶Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390.;the ‖Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75080, and ;the **Veterans Affairs North Texas Health Care System, Dallas, Texas 75216 |
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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 positions 4–6 of glucosyl units but none in positions 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-13C3]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. |
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Keywords: | Glycerol Heart Metabolism Isotopic Tracers NMR Pentose Pathway Transaldolase |
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