Regulation of CPT I activity in intermyofibrillar and subsarcolemmal mitochondria from human and rat skeletal muscle.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study on isolated human and rodent skeletal muscle mitochondria
PubMed 12954596 · doi:10.1152/ajpendo.00237.2003
What was done
Researchers measured carnitine palmitoyltransferase I (CPT I) activity in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondria isolated from human vastus lateralis (VL), rat soleus (Sol), and rat red gastrocnemius (RG) muscles. They tested whether exercise-related concentrations (~65% maximal oxygen uptake) of calcium and adenylate charge metabolites (free AMP, ADP, Pi), or reducing pH from 7.1 to 6.8, could override malonyl-CoA (M-CoA) inhibition of CPT I.
What was found
Protein content was approximately 25-40% higher in IMF than SS mitochondria in all muscles. Maximal CPT I activity was similar in IMF and SS mitochondria across all muscles (VL: 282 +/- 46 vs. 280 +/- 51; Sol: 390 +/- 81 vs. 368 +/- 82; RG: 252 +/- 71 vs. 278 +/- 44 nmol.min-1.mg protein-1). Sensitivity to M-CoA did not differ between IMF and SS mitochondria (25-31% inhibition in VL; 52-70% in Sol and RG). Exercise-related calcium and adenylate charge metabolites did not override M-CoA inhibition in any muscle fraction. Decreasing pH from 7.1 to 6.8 reduced CPT I activity by approximately 34-40% in both VL mitochondrial fractions.
Why it matters
These findings show that direct allosteric relief of malonyl-CoA inhibition by calcium or adenylate charge metabolites does not explain increased fatty acid oxidation in skeletal muscle during moderate exercise.
Limits
The abstract does not report sample sizes for human subjects or animals. The experiments were conducted in vitro on isolated mitochondria, which removes intact cytosolic architecture, physiological cellular compartmentalization, and other potential in vivo regulators.
Cited by
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