Petrick 2019 Biochem J

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Petrick HL, Holloway GP (2019) High intensity exercise inhibits carnitine palmitoyltransferase-I sensitivity to L-carnitine. Biochem J 476:547-58.

» PMID: 30635360 » O2k-brief

Petrick HL, Holloway GP (2019) Biochem J

Abstract: 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 to 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 were 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, modelling the in vivo concentrations of L-carnitine and P-CoA during exercise suggest 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.

©2019 The Author(s).

Keywords: CPT-I flux, Exercise, L-carnitine, Mitochondrial bioenergetics Bioblast editor: Plangger M O2k-Network Lab: CA Guelph Holloway GP


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: ADP, Phosphate, Substrate, Fatty acid  Coupling state: LEAK, OXPHOS  Pathway: F, N, NS  HRR: Oxygraph-2k 

2019-01 


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