Biocatalysts in Cancer Tissue

The accumulation of lactic acid in tumor tissue (15) suggests an inadequacy in the oxidative mechanism. A deficiency of one of the components of the oxidative mechanism, cytochrome c, was demonstrated in the first paper of this series (6). The present article reports the decreased activities of succinic dehydrogenase and of cytochrome oxidase in tumor tissues. These enzymes together with cytochrome c constitute the known biocatalysts of the succinoxidase system. In this system succinic acid is oxidized to fumaric acid by the catalytic removal of two atoms of hydrogen from each mole of succinate. The electrons from this hydrogen are transferred to oxidized cytochrome c via succinic dehydrogenase and from the reduced cytochrome c to molecular oxygen via cytochrome oxidase. As was emphasized previously (6) a deficiency of cytochrome c alone could account for the accumulation of lactic acid in tumor tissue. The present demonstration of a deficiency of succinic dehydrogenase and of cytochrome oxidase in tumor tissue provides further basis for lactate accumulation since the succinoxidase system is an integral part of the normal oxidative mechanism (the Krebs citric acid cycle). A decrease in the activity of this system would necessarily result in a decreased activity of the whole cycle since the reaction rate of the cycle is determined by the reaction rate of the slowest system in the cycle. The question naturally arises whether the components of this system are sufficiently decreased to account for the Q o~ of tumor tissue. This point will be discussed later in more detail. Numerous papers have appeared describing succinic dehydrogenase and cytochrome oxidase activities of various tissues. The most extensive of these re-