Metabolic inflexibility was first described as the ability to generate energy through either aerobic or anaerobic respiration[1] or as the inability of muscle to increase glucose oxidation in response to insulin.
[3] By this definition, metabolic flexibility can be quantified using respiratory quotient.
[4] This form of metabolic flexibility is reduced by insulin resistance.
[5] With aging there is a decrease in metabolic flexibility due to a decline in pyruvate dehydrogenase activity which results in pyruvate increasingly being anaerobically converted to lactate rather than aerobically converted to acetyl-CoA.
[6] Similarly, a virus-induced cytokine storm can compromise metabolic flexibility by inactivating the pyruvate dehydrogenase complex and other enzymes.