Patterns of amino acid biosynthesis from labeled glucose.

Glucose may be metabolized through the Embden-Myerhof glycolytic sequence to the threecarbon compounds, pyruvate and lactate. Alternatively, some of the glucose may be converted (a) to pentose via the hexose monophosphate shunt (1~) or (b) to serine and glycine by a series of reactions which probably branch from glycolysis at the level of phosphoglyceric acid (1, ~, 7, 8). The pyruvate and lactate which are formed glycolytically or as a result of the further metabolism of some of the pentose (1~) may in turn be metabolized through the citric acid cycle. The carbon atoms of the glycine and serine which have been formed from glucose may be utilized for the synthesis of nucleotide purines and the methyl group of thymine [15). Pentose is, of course, a constituent of the nucleotide molecule. It has been suggested that neoplastic tissues are characterized by a permanent imbalance between those enzymes which utilize essential metabolites in the growth process and the enzymes which convert the metabolites to pathways not involved in growth (13). Working with intact rats bearing the Flexner-Jobling carcinoma, Schmitz et al. (13, 14) found higher rates of nucleic acid and free nucleotide synthesis from glucose-l-C ~4 by the tumor than by several normal tissues of the rat. In connection with the above-mentioned hypothesis, it was of interest to inquire whether the alternative pathways of glucose utilization leading to (a) pen-tose formation, (b) glycine and serine formation, and (c) intermediates of the citric acid cycle and related amino acids were also different in normal as compared with neoplastic tissues. Recently, Villavicencio and Barron (16) have observed that the activity of hexokinase and the enzymes of the hexosemonophosphate shunt of lymphosarcoma cell extracts are several times greater than the activity of the enzymes from extracts of normal lymphatic tissues. Related experiments by Kit (9) indicated that pentose was formed more rapidly from labeled glucose by lymphosarcoma and ascites tumor cells than by