Journal
BIOCHEMICAL JOURNAL
Volume 448, Issue -, Pages 13-20Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20121110
Keywords
carnitine palmitoyltransferase I (CPT-I); isolated mitochondrion; malonyl-CoA; palmitoyl-CoA; permeabilized muscle fibre; skeletal muscle
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Ontario Research Fund
- NSERC
- Carleton University
- United States Public Health Service [R01 DK073488, DK074825, R01 AG028930, AK089312, HL101189]
Ask authors/readers for more resources
Published values regarding the sensitivity (IC50) of CPT-I (carnitine palmitoyltransferase 1) to M-CoA (malonyl-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 various P-CoA (palmitoyl-CoA) concentrations in both isolated mitochondria and PMFs (permeabilized muscle fibres). PMFs have an 18-fold higher IC50 (0.61 compared with 0.034 mu M) in the presence of 25 mu M P-CoA and a 13-fold higher IC50 (6.3 compared with 0.49 mu M) in the presence of 150 mu M P-CoA compared with isolated mitochondria. M-CoA inhibition kinetics determined in PMFs predicts that CPT-I activity is inhibited by 33% in resting muscle compared with >95% in isolated mitochondria. Additionally, the ability of M-CoA to inhibit CPT-1 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 PMFs appears to provide an M-CoA IC50 that better reflects the predicted in vivo rates of fatty acid oxidation. These findings also demonstrate that the ratio of [P-CoAKM-CoA] is critical for regulating CPT-1 activity and may partially rectify the in vivo disconnect between M-CoA content and CPT-I flux within the context of exercise and Type 2 diabetes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available