Pyruvate Dehydrogenase,the Citrate Condensing Enzyme and the Utilization of 14 C-Labeled Lactate,Pyruvate and Alanine by Slices of Lactating Mammary Gland and Adenocarcinoma of Mouse Mammary Gland 1

Abstract

Summary

The utilization of ¹⁴C-labeled lactate, pyruvate and alanine by tissue slices of lactating mouse mammary gland and adenocarcinoma of the mouse mammary gland was investigated. In the absence of glucose, rates of ¹⁴CO₂ formation and fatty acid synthesis from these substrates in the mammary adenocarcinoma were considerably lower than those in the lactating mammary gland, regardless of the position of the labeled carbon. In the lactating mammary gland, addition of glucose caused a considerable decline in ¹⁴CO₂ formation from the second and third carbons of lactate, pyruvate and alanine, while it significantly stimulated their incorporation into fatty acids. Glucose also stimulated ¹⁴CO₂ formation from the first carbon of these substrates. In the mammary adenocarcinoma, however, ¹⁴CO₂ formation from the first carbon of lactate and pyruvate decreased upon glucose addition, while that from the second and third carbons was almost unaffected. The incorporation into fatty acids of the second and third carbons from these substrates in the neoplasm was only slightly stimulated by glucose. Lactate uptake by lactating mammary gland was twice that observed in the mammary adenocarcinoma, but amino acid formation from this substrate was significantly higher in the neoplasm. The synthesis of glutamine, however appears to be defective in the mammary adenocarcinoma. The data indicated considerably lower levels of pyruvate dehydrogenase (EC 1.2.4.1) and citrate condensing enzyme (EC 4.1.3.7), and possibly higher acetyl-CoA deacylase (EC 3.1.2.1) activities in the tumor than in the lactating mammary gland. The significance of this finding in relation to the entry of 3-carbon glycolytic intermediates into the Krebs cycle in both the lactating mammary gland and the mammary adenocarcinoma is discussed.