Microvascular O2 delivery and O2 utilization during metabolic transitions in skeletal muscle. One-hundred years after the pioneering work by August Krogh.
Comp Biochem Physiol A Mol Integr Physiol
; 252: 110842, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33212294
ABSTRACT
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 VÌO2 kinetics during transitions to submaximal metabolic rates. VÌO2 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 VÌO2 kinetics was observed only for creatine kinase (CK) mediated phosphocreatine (PCr) breakdown. Following CK inhibition, faster muscle VÌO2 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 VÌO2 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.
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Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Músculo Esquelético
Limite:
Animals
Idioma:
En
Revista:
Comp Biochem Physiol A Mol Integr Physiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article