Studies on Energy-yielding Reactions in Thymus Nuclei : II. PATHWAYS OF AEROBIC CARBOHYDRATE CATABOLISM.

The means by which cell nuclei obtain free energy for RNA, DNA, and protein synthesis and other processes is a question of considerable importance to our understanding of cellular physiology and function. Mitochondria are known to have a highly organized, membrane-bound system for the oxidative phosphorylation of adenosine diphosphate to adenosine triphosphate. Our observations point to the conclusion that nuclei from at least one mammalian tissue, namely, the thymus gland, also have a system for the oxygen-dependent synthesis of adenosine triphosphate (1,2). Evidence for an independent nuclear phosphorylation system was presented in the first paper of this series (2) in which a direct comparison of nuclei and mitochondria from the thymus gland showed that mitochondria cannot account for the ATP synthesis which occurs in suspensions of thymus nuclei. The nuclear system is sensitive to many of the same inhibitors which block mitochondrial oxidative phosphorylation but differs from this process by being insensitive to carbon monoxide, calcium ions, and methylene blue and sensitive to treatment of the nuclei with DNase (2). The purpose of this paper is to present evidence that three major pathways of carbohydrate catabolism, the hexose monophosphate shunt, glycolysis, and the citric acid cycle, are all present in thymus nuclei. The operation of the citric acid cycle involves succinic dehydrogenase, and evidence is presented that this enzyme is found in thymus nuclei as well as in thymus mitochondria. In much of the work to be described we used nuclei isolated in nonaqueous solvents, a procedure which has been shown to provide the most reliable information about the localization of water-soluble substances within nuclei (3). Evidence from other laboratories, which will be discussed, indicates that nuclei from a wide variety of other tissues also contain enzymes of these three pathways. The third paper of this series, which follows this one, presents evidence that glycolysis and the citric acid cycle participate in the aerobic ATP synthesis occurring in suspensions of isolated intact thymus nuclei.