PATHWAY OF FREE FATTY-ACID OXIDATION IN HUMAN-SUBJECTS IMPLICATIONS FOR TRACER STUDIES

To determine the pathway of plasma FFA oxidation and the site(s) of la bel fixation observed during infusion of FFA tracers, [1-C-13]palmitat e and [1-C-14]acetate were infused intravenously for 3 h in five volun teers. Breath (CO2)-C-13 enrichment and (CO2)-C-14 specific activity w ere followed for 6 h to determine the labeled CO2 decay rates. Acetate enters directly into the TCA cycle; hence, if palmitate transits a la rge lipid pool before oxidation, (CO2)-C-13 enrichment (from palmitate ) should decay slower than (CO2)-C-14 specific activity (from acetate) . Breath (CO2)-C-13 enrichment and (CO2)-C-14 specific activity decaye d at a similar rate after stopping the tracer infusions (half-lives of (CO2)-C-13 and (CO2)-C-14 decay: mean [+/-SE] 106.6+/-8.9 min, and 96 .9+/-6.0 min, respectively, P = NS), which suggests that palmitate ent ers the TCA cycle directly and that label fixation occurs after citrat e synthesis. Significant label fixation was shown in plasma glutamate/ glutamine and lactate/pyruvate during infusion of either [1,2-C-13]ace tate or [U-C-13]palmitate, suggesting that TCA cycle exchange reaction s are at least partly responsible for label fixation. This was consist ent with our finding that the half-lives of (CO2)-C-13 enrichment and (CO2)-C-14 specific activity decreased significantly during exercise t o 14.4+/-3 min and 16.8+/-1 min, respectively, since exercise signific antly increases the rate of the TCA cycle in relation to that of the T CA cycle exchange reactions. We conclude that plasma FFA entering cell s destined to be oxidized are directly oxidized and that tracer estima tes of plasma FFA oxidation will underestimate the true value unless a ccount is taken of the extent of label fixation.