A 13c isotopomer model for estimation of anaplerotic substrate
oxidation via acetyl-coa.
Jeffrey, F. Mark H., Charles J. Storey, A. Dean Sherry, and Craig R.
Malloy.
Department of Radiology and Department of Internal Medicine,
Division of Cardiology, UT Southwestern Medical Center, The Mary Nell
and Ralph B. Rogers Magnetic Resonance Center, and Dallas Veterans
Affairs Medical Center, Dallas, TX 75235-9085 and Department of
Chemistry, University of Texas at Dallas, Richardson, TX 75083
-0688
APStracts 3:0125E, 1996.
A previous model using 13C NMR isotopomer analysis provided for direct
measurement of the oxidation of 13C-enriched substrates in the citric
acid cycle, and/or their entry via anaplerotic pathways. This model
did not allow for recycling of labeled metabolites from citric acid
cycle intermediates into the acetyl-CoA pool. An extension of this
model is now presented which 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 the propionate consumed was oxidized to CO2 and
water. Application of the new isotopomer model shows that 2 mM [3
-13C]propionate entered the citric acid cycle as succinyl-CoA (an
anaplerotic pathway) at a rate equal to 52% of citric 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 ([mu]mole/min/g dry weight) of propionate uptake (4.0
+/- 0.7), the estimated oxygen consumption (24.8 +/- 5) matched that
experimentally determined (24.4 +/- 3).
Received 5 May 1995; accepted in final form 14 June 1996.
APS Manuscript Number E207-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96