ION GRADIENTS AND METABOLIC ENERGY IN ANIMAL TISSUE

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Our metabolic control analysis of glucose flux in the perfused rat heart led to an editorial detailing the artifacts resulting from the use of [2-(18)F]fluoro-2-deoxy-d-glucose in cardiac imaging as we had previously discussed in brain imaging. In a combined NMR and metabolic study, we demonstrated that a physiological ratio of ketone bodies could alter the redox state of the mitochondrial pyridine nucleotide and Co-Q couples, thus mimicking the action of insulin resulting in an increase in the delta G of ATP hydrolysis and a remarkable 35 percent increase in the efficiency of hydraulic work in the isolated working rat heart. Ketones differed from insulin in their ability to lower the electric potential between mitochondrial and cytosolic phases and decrease the mitochondrial accumulation of inorganic phosphate and magnesium. Having previously demonstrated the hyperpolarization which occurs in liver co-incident with the metabolism of ethanol and the resultant loss of magnesium from liver, we developed a new method for the non-invasive estimation of free [Mg(2+)] and pH from the peak height ratios of the beta/alpha resonances of ATP and the chemical shift difference of inorganic Pi. In this paper we showed that the method, used for the past two decades, utilizing the chemical shift difference of the beta-alpha resonances was insensitive within the physiological range. Important clinical studies involving the use of magnesium therapy during withdrawal and more significantly, studies of the use of intravenous magnesium therapy prior to reperfusion after acute coronary occlusion, may require re-evaluation in the light of these new findings. In another aspect of the relationship of inorganic ions to metabolic energy, the shortcomings of existing methods of resuscitation were discussed and a discussion of the relationship between metabolic energy, the gradients of inorganic ions and the variable electric potential between the extra and intracellular phases of the cell was presented.