AJP - Endocrinology and Metabolism, Vol 271, Issue 4 E788-E799, Copyright © 1996 by American Physiological Society
13C isotopomer model for estimation of anaplerotic substrate oxidation via acetyl-CoA
F. M. Jeffrey, C. J. Storey, A. D. Sherry and C. R. Malloy
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, USA.
A previous model using 13C nuclear magnetic resonance isotopomer analysis
provided for direct measurement of the oxidation of 13C-enriched substrates
in the tricarboxylic acid cycle and/or their entry via anaplerotic
pathways. This model did not allow for recycling of labeled metabolites
from tricarboxylic acid cycle intermediates into the acetyl-CoA pool. An
extension of this model is now presented that incorporates carbon flow from
oxaloacetate or malate to acetyl-CoA. This model was examined using
propionate metabolism in the heart, in which previous observations
indicated that all of the propionate consumed was oxidized to CO2 and
water. Application of the new isotopomer model shows that 2 mM
[3-13C]propionate entered the tricarboxylic acid cycle as succinyl-CoA (an
anaplerotic pathway) at a rate equal to 52% of tricarboxylic acid cycle
turnover and that all of this carbon entered the acetyl-CoA pool and was
oxidized. This was verified using standard biochemical analysis; from the
rate (mumol.min-1.g dry wt-1) of propionate uptake (4.0 +/- 0.7), the
estimated oxygen consumption (24.8 +/- 5) matched that experimentally
determined (24.4 +/- 3).
