Aspects of human bioenergetics as studied in vivo by magnetic resonance spectroscopy

We outline the relevant capabilities of in vivo phosphorus MR spectroscopy by discussing some aspects of normal human biochemistry as studied by this technique. The transport of inorganic phosphate from cytosol into mitochond ria in the human skeletal muscle was studied by exploiting a new experiment al protocol. We found that Pi was transported into mitochondria in the abse nce of ATP biosynthesis and in the presence of a pH gradient. The control o f CoQ on the efficiency of oxidative phosphorylation in the skeletal muscle and brain was studied by administering CoQ to patients with mitochondrial cytopathies due to known enzyme defects. Before CoQ we had detected a relev ant reduction of mitochondrial functionality in the skeletal muscle as show n by the reduced rate of phosphocreatine recovery from exercise, and in the occipital lobes by reduced [phosphocreatine] and a high [ADP] and [Pi]. Af ter CoQ all brain variables were remarkably improved. Treatment with CoQ al so improved the rate of muscle phosphocreatine recovery from exercise. Our in vivo findings support the hypothesis that the concentration of CoQ rathe r than the rate of its lateral diffusion in the mitochondrial membrane cont rols the efficiency of oxidative phosphorylation. Other experiments were un dertaken to clarify the functional relationship between cytosolic free [Mg2 +] and cell bioenergetics in the intact human brain. In the same group of p atients with mitochondrial cytopathies we found decreased Delta G of ATP hy drolysis and low cytosolic free [Mg2+]. Treatment with CoQ resulted in impr oved brain bioenergetics and increased free [Mg2+]. These findings strongly indicate that decreased free magnesium was secondary to defective mitochon drial respiration, and support the hypothesis that cytosolic free [Mg2+] is regulated in the intact brain cell to equilibrate, at least in part any ch anges in rapidly available free energy. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris.