The effects of high fatty acid on the glucose metabolism of Ehrlich ascites tumor cells.

The effects of high fatty acids such as oleic, richinoleic, linoleic, linolenic, palmitic and stearic acids, on the respiration, glycolysis, organic phosphate synthesis of Ehrlich ascites tumor cells, were studied. The unsaturated fatty acids added to the media enhanced the respiration of the tumor cells at the concentration lower than 0.2 mM, after a short incubation period and inhibited the respiration in a high concentration 0.4 mM. The saturated fatty acids did not show such effect. All the fatty acids, both of saturated and unsaturated, effected the increase in lactate formation in tumor cells, especially markedly at higher concentration being accompanied by the WQ increase and RQ around 1. The respiration lowered by the fatty acids was ameliorated by the addition of glucose. The lactate formation from glucose was greatly enhanced by the addition of fatty acids but hardly from pyruvate. The unsaturated high fatty acids proved to have a strong uncoupling action for oxidative phosphorylation. This effect could be recognized slightly in the saturated fatty acids. The addition of high fatty acid resulted in the striking decrease in ATP and ADP with the increase in AMP. With these results the discussion was conducted concerning the specificity of tumor cell related to the glucose and fatty acid metabolism. ∗PMID: 13995580 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 16, 177-191 (1962} THE EFFECTS OF HIGH FATTY ACID ON THE GLUCOSE METABOLISM OF EHRLICH ASCITES TUMOR CELLS* Kozo UTSUMI, Kozo INABA, Michio YAMAMOTO, Goki YAMAMOTO, Hiroyuki URAKAMI and Satimaru SENO Department of Biochemistry of Cancer Institute and Department of Pathology, Okayama University Medical School, Okayama Received for publication, July 6, 1962 One of the specificities of cancer cell may be found in its respiratory metabolism on the endogenous substratel-l'. This endogenous respiration of cancer cell is something of longstanding comparing with that of normal cell, e. g. the respiration of Ehrlich ascites tumor cell frequently lasts more than 6 to 10 hours with slow decrease in activity12,13 as observed in vitro, whereas the respiration of normal cell, mouse liver cell, lasts only 2 to 3 hours at most under the same condition. However, the respiration of tumor cell is hardly accelerated by glucose or the members of citric acid cycle but it decreases by adding glucose or fructose differing from the case of normal cell whose respiration is generally enhanced by adding glucose or the members of citric acid cycle. This phenomenon is well known as Crabtree effect. For a long time this effect has been studied by many biochemists and is currently understood as the result of extraordinarily accelerated cytoplasmic glycolysis in cancer cell which will result out of the compartmentation in ADP and Pi between cytoplasm and mitochondria9,14.16, and then the decreased respiration. However, it might be noticed that in cancer cells the endogenous respiration is largely dependent on fatty acid oxidation, more than 30 per cent as WEINHOUS and associates stated. Their studies on lipid metabolism using He-palmitate, also show that more than one half of energetic metabolism of cancer cell is dependent upon lipids. • This specific metabolism of cancer cell might be correlated with Crabtree effect. The free fatty acids added from the outside of cells may act as an uncoupling agent on the oxidative phosphorylation accelerating the respiration at their lower concentrations, differently from the endogenous fatty acid (SCHOLEFIELD9,1B and LEHNINGER19, etc.). Our studies revealed the enhancing effect of saturated and unsaturated fatty acids for the glycolysis and suppressing effect for oxidative phosphorylation of tumor cells. These facts suggest a close connection between glucose and fatty acid metabolism in tumor cell. In this paper the effects of fatty acids on glycolytic metabolism of Ehrlich ascites tumor cell are presented. * This work was supported by a grant (CA·6146-l) from the National Institute for Cancer, National Institutes of Health, United States Public Health Service, Department of Health, Education and Welfare.