Coupling of Mitochondrial Fatty Acid Uptake to Oxidative Flux in the Intact Heart

AbstractThe coordination of long chain fatty acid (LCFA) transport across the mitochondrial membrane (VPAL) with subsequent oxidation rate through β-oxidation and the tricarboxylic acid (TCA) cycle (Vtca) has been difficult to characterize in the intact heart. Kinetic analysis of dynamic 13C-NMR distinguished these flux rates in isolated rabbit hearts. Hearts were perfused in a 9.4 T magnet with either 0.5mM [2,4,6,8,10,12,14,16-13C8] palmitate (n=4), or 0.5mM 13C-labeled palmitate plus 0.08mM 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 VTCA to VPAL 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; VTCA/VPAL=12:1 due to an SCFA-induced increase in VTCA of 43% (p