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Research Article Free access | 10.1172/JCI109860

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

Françoise Féry and Edmond O. Balasse

Metabolic Unit, Hôpital St. Pierre, 1000 Brussels, Belgium

Laboratory of Experimental Medicine, University of Brussels, 1000 Brussels, Belgium

Find articles by Féry, F. in: PubMed | Google Scholar

Metabolic Unit, Hôpital St. Pierre, 1000 Brussels, Belgium

Laboratory of Experimental Medicine, University of Brussels, 1000 Brussels, Belgium

Find articles by Balasse, E. in: PubMed | Google Scholar

Published August 1, 1980 - More info

Published in Volume 66, Issue 2 on August 1, 1980
J Clin Invest. 1980;66(2):323–331. https://doi.org/10.1172/JCI109860.
© 1980 The American Society for Clinical Investigation
Published August 1, 1980 - Version history
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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.

If the hyperalaninemic and hyperglutaminemic effects of ketone bodies infused in their physiological form (free acids) reflect a stimulation of the muscular output of these amino acids, the participation of ketone bodies in the nitrogen-sparing process of prolonged fasting seems very unlikely. On the other hand, during brief starvation, when both ketogenesis and gluconeogenesis are markedly stimulated, ketone bodies might indirectly contribute in supplying the liver and the kidney with gluconeogenic substrates.

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