Some aspects of the metabolism of pyruvic acid in the intact animal.

Until the advent of the isotope technique, the formation of fat in adult animals was held to occur only on a diet containing an excess of calories. From the work of Schoenheimer and Rittenberg (1) it became clear that body fat is not an inert energy store but participates actively in intermediary metabolism. Their evidence also indicated that small molecules were utilized to build up the fatty acid chains as well as the cholesterol structure. The observation that carbohydrate can serve as a precursor for body fat is very old, and many investigations have been carried out to analyze the details of this process. It is clear that on a balance basis fat must ultimately be derived from the carbohydrate or protein of the diet if no fat is supplied in the food, Stetten and Boxer (2) concluded from experiments with heavy water that a large portion of dietary carbohydrate is metabolized by way of fat. These authors (3) proposed too that interference with fatty acid synthesis is one of the main metabolic defects in alloxan diabetes. Investigations by Bloch and Rittenberg (4, 5) revealed the importance of acetic acid as a precursor in the synthesis of fatty acids and cholesterol and established the quantitative significance of acetic acid as a major intermediate of metabolism. Smedley and Lubrzynska (6) first suggested pyruvic acid as an important intermediate in carbohydrate metabolism, and many investigations since have borne out the central role of pyruvic acid in glycolysis. It seems likely that pyruvic acid is also a key intermediate in the conversion of carbohydrate to other body constituents. The work presented here was undertaken to ascertain directly the utilization of pyruvic acid for the various metabolic processes, particularly the synthesis of acetic acid, fatty acids, and cholesterol. For this purpose pyruvic acid labeled in the the carbonyl carbon with Cl4 was synthesized and fed to rats. Feeding experiments were also carried out with carboxyl-labeled pyruvic acid and labeled acetic acid.