Coupling of mitochondrial fatty acid uptake to oxidative flux in the intact heart.
The coordination of long chain fatty acid (LCFA) transport across the mitochondrial membrane (V(PAL)) with subsequent oxidation rate through beta-oxidation and the tricarboxylic acid (TCA) cycle (V(tca)) has been difficult to characterize in the intact heart. Kinetic analysis of dynamic (13)C-NMR distinguished these flux rates in isolated rabbit hearts. Hearts were perfused in a 9.4 T magnet with either 0.5 mM [2,4,6,8,10,12,14,16-(13)C(8)] palmitate (n = 4), or 0.5 mM (13)C-labeled palmitate plus 0.08 mM unlabeled butyrate (n = 4). Butyrate is a short chain fatty acid (SCFA) that bypasses the LCFA transporters of mitochondria. In hearts oxidizing palmitate alone, the ratio of V(TCA) to V(PAL) was 8:1. This is consistent with one molecule of palmitate yielding eight molecules of acetyl-CoA for the subsequent oxidation through the TCA cycle. Addition of butyrate elevated this ratio; V(TCA)/V(PAL) = 12:1 due to an SCFA-induced increase in V(TCA) of 43% (p < 0.05). However, SCFA oxidation did not significantly reduce palmitate transport into the mitochondria: V(PAL) = 1.0 +/- 0.2 micromol/min/g dw with palmitate alone versus 0.9 +/- 0.1 with palmitate plus butyrate. Thus, the products of beta-oxidation are preferentially channeled to the TCA cycle, away from mitochondrial efflux via carnitine acetyltransferase.
O'Donnell
J Michael
JM
Program in Integrative Cardiac Metabolism, Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois 60612-7342, USA.
Alpert
Nathaniel M
NM
White
Lawrence T
LT
Lewandowski
E Douglas
ED
D000818:Animals; D002087:Butyrates / Q000378:metabolism; D002952:Citric Acid Cycle; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D008962:Models, Theoretical; D009200:Myocardial Contraction / Q000502:physiology*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D011817:Rabbits
D002087:Butyrates; D005230:Fatty Acids, Nonesterified; D019308:Palmitic Acid