title: Coupling of mitochondrial fatty acid uptake to oxidative flux in the intact heart.
abstract: 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.
authors.affiliation: Program in Integrative Cardiac Metabolism, Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois 60612-7342, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: O'Donnell
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Alpert
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: White
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: 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
chemical_list: D002087:Butyrates; D005230:Fatty Acids, Nonesterified; D019308:Palmitic Acid