Microvascular O2 delivery and O2 utilization during metabolic transitions in skeletal muscle. One-hundred years after the pioneering work by August Krogh
| Autor: | L. Bruce Gladden, Bruno Grassi, Michael C. Hogan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Bioenergetics Physiology deficit Oxidative phosphorylation Microvascular O 2 delivery O Regulation of oxidative phosphorylation Skeletal muscle bioenergetics Biochemistry Phosphocreatine 03 medical and health sciences Substrate-level phosphorylation chemistry.chemical_compound Gastrocnemius muscle 0302 clinical medicine Internal medicine medicine Molecular Biology biology Chemistry Skeletal muscle 030229 sport sciences Pyruvate dehydrogenase complex medicine.anatomical_structure Endocrinology biology.protein Creatine kinase 030217 neurology & neurosurgery |
| Popis: | Upon a sudden rise in work rate, ATP turnover increases immediately, whereas the adjustment of ATP resynthesis from oxidative phosphorylation is substantially slower. An "O2 deficit" (energy borrowed from substrate level phosphorylation) is therefore generated. A greater O2 deficit represents an epiphenomenon of a lower "metabolic stability" during the transition, a circumstance directly related to impaired exercise tolerance. In the search for factors responsible for the delayed adjustment of oxidative phosphorylation, we performed studies in the surgically isolated canine gastrocnemius muscle in situ. Enhancement of convective and diffusive microvascular O2 delivery, with respect to a "normal" condition, did not affect skeletal muscle VO2 kinetics during transitions to submaximal metabolic rates. VO2 kinetics, however, was slowed after experimentally impairing convective O2 delivery, a condition frequently encountered in pathological conditions. Among potential metabolic factors (pyruvate dehydrogenase activation, nitric oxide inhibition of cytochrome oxidase) a limiting role in VO2 kinetics was observed only for creatine kinase (CK) mediated phosphocreatine (PCr) breakdown. Following CK inhibition, faster muscle VO2 kinetics was observed. Thus, in skeletal muscle CK-catalysed PCr breakdown at contractions onset slows the increase of oxidative phosphorylation. By acting as a high-capacitance energy buffer, PCr breakdown delays or attenuates the increased concentrations of metabolites (such as ADP, Pi, Cr) mediating the VO2 increase. Upon sudden increases in ATP turnover, skeletal muscle fibers rely first on the bioenergetic pathway (PCr breakdown), which is fast to adjust to increased metabolic needs. Metabolites related to PCr breakdown regulate, but inevitably slow down, the adjustment of oxidative phosphorylation. |
| Databáze: | OpenAIRE |
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