Differential Effects of Sodium Acetoacetate and Acetoacetic Acid Infusions on Alanine and Glutamine Metabolism in Man

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Abstract

It has been suggested that ketone bodies might participate in the nitrogen-sparing process occurring during prolonged starvation by inhibiting the muscular production of alanine and glutamine, which are the main gluconeogenic amino acids. The results of the ketone infusion studies on which this theory is based have been reevaluated in this study by following the plasma levels of ketone bodies, alanine, glutamine, and other substrates during 11.5 h in five groups of normal overnight-fasted subjects. Subjects of groups I, II, and III were infused for 3 h, respectively, with Na acetoacetate, Na bicarbonate, or free acetoacetic acid administered in comparable amounts (about 20 μmol/kg per min), whereas group IV was infused with hydrochloric acid (7.0 μmol/kg per min). A control group (V) received no infusion. Na acetoacetate induced a rise in blood pH (+0.1±0.003) and a fall in the plasma levels of alanine (−41.8±4.6%) and glutamine (−10.6±1.4%), whereas free acetoacetic acid had a barely detectable lowering effect on blood pH and induced a rise in alanine (+22.5±8.0%) and glutamine (+14.6±3.2%) levels. Both infusions were associated with a lowering of plasma glucose, which therefore seems independent of the changes in alanine and glutamine concentrations. Sodium bicarbonate reproduced the alkalinizing effect and the hypoalaninemic action of Na acetoacetate, which seems thus unrelated to hyperketonemia. On the other hand, acidification of blood with hydrochloric acid did not mimic the effects of acetoacetic acid.

Authors

Françoise Féry, Edmond O. Balasse