Improved estimation of anaplerosis in heart using 13C NMR

The American Journal of Physiology
D M Cohen, R N Bergman

Abstract

Anaplerotic enzymes, such as pyruvate carboxylase or malic enzyme, catalyze reactions that fill up the pools of the citric acid cycle (CAC), thereby increasing the total mass of CAC intermediates. Relative anaplerosis (y) denotes the ratio of anaplerotic flux to the flux catalyzed by citrate synthase. We examine conventional methods [C. R. Malloy, A. D. Sherry, and F. M. H. Jeffrey. J. Biol. Chem. 263:6964-6971, 1988; C. R. Malloy, A. D. Sherry, and F. M. H. Jeffrey. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H987-H995, 1990] of measurement of y using 13C-labeled precursors and analysis of [13C]glutamate labeling by nuclear magnetic resonance (NMR) spectroscopy. Through mathematical analysis and computer simulation, we show that isotopic enrichment of the pool of pyruvate that is substrate for anaplerosis will severely decrease the accuracy of estimates of y made with conventional methods no matter how small the mass of the pool of pyruvate. Suppose that the recycling parameter R denotes the fraction of molecules of pyruvate that contain carbons derived from intermediates of the CAC. Each means of estimation of relative anaplerosis in the peer-reviewed literature assumes that R = O, although this assumption has not been con...Continue Reading

References

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Citations

Oct 14, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Aaron K OlsonMichael A Portman
Aug 29, 2003·American Journal of Physiology. Endocrinology and Metabolism·David M CohenHeinrich Taegtmeyer
Oct 25, 2000·American Journal of Physiology. Heart and Circulatory Physiology·A R PanchalW C Stanley

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