High intensity exercise inhibits carnitine palmitoyltransferase-I sensitivity to l -carnitine
Autor: | Graham P. Holloway, Heather L. Petrick |
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Rok vydání: | 2019 |
Předmět: |
medicine.medical_specialty
Bioenergetics Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Carnitine Physical Conditioning Animal Internal medicine medicine Animals Molecular Biology Palmitoylcarnitine 030304 developmental biology computer.programming_language 0303 health sciences Carnitine O-Palmitoyltransferase Chemistry sed Skeletal muscle 030229 sport sciences Cell Biology Mitochondria Muscle Adenosine diphosphate medicine.anatomical_structure Endocrinology Carnitine palmitoyltransferase I Flux (metabolism) computer medicine.drug |
Zdroj: | Biochemical Journal. 476:547-558 |
ISSN: | 1470-8728 0264-6021 |
Popis: | The decline in fat oxidation at higher power outputs of exercise is a complex interaction between several mechanisms; however, the influence of mitochondrial bioenergetics in this process remains elusive. Therefore, using permeabilized muscle fibers from mouse skeletal muscle, we aimed to determine if acute exercise altered mitochondrial sensitivity to (1) adenosine diphosphate (ADP) and inorganic phosphate (Pi), or (2) carnitine palmitoyltransferase-I (CPT-I) independent (palmitoylcarnitine, PC) and dependent [palmitoyl-CoA (P-CoA), malonyl-CoA (M-CoA), and l-carnitine] substrates, in an intensity-dependent manner. As the apparent ADP Km increased to a similar extent following low (LI) and high (HI) intensity exercise compared with sedentary (SED) animals, and Pi sensitivity was unaltered by exercise, regulation of phosphate provision likely does not contribute to the well-established intensity-dependent shift in substrate utilization. Mitochondrial sensitivity to PC and P-CoA was not influenced by exercise, while M-CoA sensitivity was attenuated similarly following LI and HI. In contrast, CPT-I sensitivity to l-carnitine was only altered following HI, as HI exercise attenuated l-carnitine sensitivity by ∼40%. Moreover, modeling the in vivo concentrations of l-carnitine and P-CoA during exercise suggests that CPT-I flux is ∼25% lower following HI, attributed equally to reductions in l-carnitine content and l-carnitine sensitivity. Altogether, these data further implicate CPT-I flux as a key event influencing metabolic interactions during exercise, as a decline in l-carnitine sensitivity in addition to availability at higher power outputs could impair mitochondrial fatty acid oxidation. |
Databáze: | OpenAIRE |
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