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 label fixation observed during infusion of FFA tracers, [1-C-13]palmitate and [1-C-14]acetate were infused intravenously for 3 h in five volunteers. Breath (CO2)-C-13 enrichment and (CO2)-C-14 specific activity were followed for 6 h to determine the labeled CO2 decay rates. Acetate enters directly into the TCA cycle; hence, if palmitate transits a large 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 decayed 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 enters the TCA cycle directly and that label fixation occurs after citrate synthesis. Significant label fixation was shown in plasma glutamate/glutamine and lactate/pyruvate during infusion of either [1,2-C-13]acetate or [U-C-13]palmitate, suggesting that TCA cycle exchange reactions are at least partly responsible for label fixation. This was consistent with our finding that the half-lives of (CO2)-C-13 enrichment and (CO2)-C-14 specific activity decreased significantly during exercise to 14.4+/-3 min and 16.8+/-1 min, respectively, since exercise significantly increases the rate of the TCA cycle in relation to that of the TCA cycle exchange reactions. We conclude that plasma FFA entering cells destined to be oxidized are directly oxidized and that tracer estimates of plasma FFA oxidation will underestimate the true value unless account is taken of the extent of label fixation.