Control of Mitochondrial Energy Production in Vivo
The study of purified enzymes and isolated mitochondria under well-defined conditions has provided a wealth of information about cellular metabolism over the past 50 years. However, results from studies on these reconstructed systems define the possible range of activity rather than the actual activity in vivo. In intact tissue the metabolic networks which we divide artificially into “glycolysis” and “oxidative phosphorylation” work as a unit, responding in concert to stimuli and effectors which are constantly in flux. The relationship of the properties of macromolecules and organelles to tissue metabolism can ultimately be understood only through non-invasive studies in vivo. 31 Phosphorus nuclear magnetic resonance (31P MRS) allows continuous measurement of the major phosphorus-containing metabolites and intracellular pH (pHi) in many tissues (Radda & Taylor, 1985; Radda et al., 1988). These metabolites are ATP, phosphocreatine (PCr), Pi, phosphodiesters (PDE) and phosphomonoesters (PME). The information on all of these variables is gathered simultaneously and without affecting the processes being investigated. This technique provides an excellent means of investigating the integration of mitochondrial activity into the overall energy metabolism of muscle. The approach in our laboratory has been to study the control and coordination of these pathways in normal and diseased human by observing with MRS the biochemical response to stress. Exercise provides an energetic demand that can be varied by intensity and duration; glycolytic, glycogenolytic and oxidative defects impose other specific metabolic stresses on cellular energetics.
KeywordsFatigue Lactate Rubber Pyruvate Fructose
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