RELATIONS OF INTRACELLULAR IONS TO METABOLITE SEQUENCES IN MUSCLE IN KWASHIORKOR

A biopsy was obtained at the time of admission and subsequently from eight children with severe kwashiorkor. The biopsies were analyzed for electrolyte content and for the quantities of certain intermediates (pyruvate, lactate, citrate and alphaketoglutarate). The results in five children who recovered are compared with those from three children who died. Significant reductions occurred in intracellular potassium, phosphate, magnesium and pyruvate, but lactate and alpha-ketoglutarate were increased. When the intracellular electrolytes were related to a specific intermediary metabolite (on the premise that the ion served as an activator or inhibitor in an enzymatic sequence leading to the production or the utilization of that intermediate) the changes assumed greater significance. A more dynamic interpretation of the data was provided by comparing ion:metabolite ratios of the initial with those of the second biopsy in patients who either recovered or died. Death from kwashiorkor was associated with a marked reversal in the sodium: pyruvate ratio and the apparent inorganic and organic phosphate to pyruvate ratios within the cell. These changes are consistent with some defect in the formation of pyruvate from phosphoenolpyruvate in a potassium-, magnesium-, phosphorus-dependent system. The citrate, magnesium and "true" inorganic phosphate to alphaketoglutarate ratios also were reversed in children who died compared to those who recovered. Such changes indicate a possible inhibition in the usual citric acid cycle pathway along which alpha-ketoglutarate is metabolized. Preliminary data on concentrations of phosphoenolpyruvate, isocitrate and oxalacetate within the muscle cell and on the activities of pyruvic kinase also are presented. The data are consistent with the hypothesis that the cellular swelling (in muscle) often characteristic of kwashiorkor leads to reduction in concentration of essential intracellular ions with inhibition of intermediary energy metabolism, thus leading to death. Since intracellular ions may function as activators or inhibitors for specific enzymes, it is suggested that changing quantities of a particular ion may be referred to the quantity of metabolite forming substrate or product of the specific enzymatic sequence. Altered ratios of ions to appropriate metabolites emphasize the possible significance of intracellular electrolytes in the biological system.