Coupling of mitochondrial fatty acid uptake to oxidative flux in the intact heart

Biophys J. 2002 Jan;82(1 Pt 1):11-8. doi: 10.1016/S0006-3495(02)75369-1.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Butyrates / metabolism
  • Citric Acid Cycle
  • Fatty Acids, Nonesterified / metabolism*
  • Intracellular Membranes / metabolism
  • Kinetics
  • Mitochondria, Heart / metabolism*
  • Models, Theoretical
  • Myocardial Contraction / physiology*
  • Oxidation-Reduction
  • Palmitic Acid / metabolism
  • Rabbits

Substances

  • Butyrates
  • Fatty Acids, Nonesterified
  • Palmitic Acid