Identification of a novel malonyl-CoA IC50for CPT-I: Implications for predicting in vivo fatty acid oxidation rates

Published values regarding the sensitivity (IC(50)) of carnitine palmitoyl transferase I (CPT-I) to malonyl-CoA (M-CoA) inhibition in isolated mitochondria are inconsistent with predicted in vivo rates of fatty acid oxidation. Therefore, we have re-examined M-CoA inhibition kinetics under varying palmitoyl-CoA (P-CoA) concentrations in both isolated mitochondria and permeabilized muscle fibres (PMF). PMF have an 18-fold higher IC(50) (0.61 vs 0.034 μM) in the presence of 25 μM P-CoA and a 13-fold higher IC(50) (6.3 vs 0.49 μM) in the presence of 150 μM P-CoA compared to isolated mitochondria. M-CoA inhibition kinetics determined in PMF predicts that CPT-I activity is inhibited by 33% in resting muscle compared to >95% in isolated mitochondria. Additionally, the ability of M-CoA to inhibit CPT-I appears to be dependent on P-CoA concentration, as the relative inhibitory capacity of M-CoA is decreased with increasing P-CoA concentrations. Altogether, the use of PMF appears to provide a M-CoA IC(50) that better reflects the predicted in vivo rates of fatty acid oxidation. These findings also demonstrate the ratio of [P-CoA]/[M-CoA] is critical for regulating CPT-I activity and may partially rectify the in vivo disconnect between M-CoA content and CPT-I flux within the context of exercise and type II diabetes

Low carbohydrate diets and performance

Athletes are continually searching for means to optimize their performance. Within the past 20 years, athletes and scientists have reported and/or observed that consuming a carbohydrate restricted diet may improve performance. The original theories explaining the purported benefits centered on the fact that fat oxidation increases, thereby "sparing" muscle glycogen. More recent concepts that explain the plausibility of the ergogenicity of low carbohydrate, or high fat, diets on exercise performance pertain to an effect similar to altitude training. We and others have observed that, while fat oxidation may be increased, the ability to maintain high intensity exercise (e.g., above the lactate threshold) seems to be compromised or at least indifferent compared to when more carbohydrate was consumed. That said, clinical studies clearly demonstrate that ad-libitum low carbohydrate diets elicit greater decreases in body weight and fat than energy equivalent low fat diets, especially over a short duration. Thus, while low carbohydrate and high fat diets appear detrimental or indifferent relative to performance, they may be a faster means to achieve a more competitive body composition