This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cederbaum, A. I. Articles by Rubin, E. Search for Related Content PubMed PubMed Citation Articles by Cederbaum, A. I. Articles by Rubin, E.

Fatty Acid Oxidation, Substrate Shuttles, and Activity of the Citric Acid Cycle in Hepatocellular Carcinomas of Varying Differentiation¹

Departments of Pathology [A. I. C., E. R.], and Biochemistry [A. I. C.], Mount Sinai School of Medicine of the City University of New York, New York, New York 10029

Fatty acid oxidation, reconstituted substrate shuttles, and the activity of the citric acid cycle were studied in mitochondria isolated from Becker transplantable hepatocellular carcinoma H-252 and host livers, and the results were compared with those obtained with Morris hepatomas 7288CTC and 5123C. Whereas the activities of the malate-aspartate and the -glycerophosphate shuttles were only slightly lower than those of host livers, the activity of the fatty acid shuttle was much lower in H-252 mitochondria. Oxygen uptake and CO₂ production associated with the oxidation of fatty acids was much lower in tumors H-252 and 7288CTC, compared with host livers, whereas tumor 5123C mitochondria show a high capacity to oxidize fatty acids. Ketogenesis and ß-hydroxybutyrate dehydrogenase activity were also lower in tumor H-252 mitochondria. However, neither oxygen uptake associated with the oxidation of other respiratory substrates nor CO₂ production from labeled citric acid cycle intermediates was impaired in tumor H-252 or 7288CTC. In fact, CO₂ production from succinate or malate was strikingly elevated in these tumors. These factors suggest that the respiratory phosphorylation chain and activity of the citric acid cycle are fully functional in tumors H-252 and 7288CTC. The defects responsible for the lower rates of fatty acid oxidation in these tumors probably involves the ß-oxidation pathway, as well as the activation of fatty acids. The impairment of fatty acid oxidation may explain the lower activity of the reconstituted fatty acid shuttle for transporting reducing equivalents into H-252 mitochondria. The different properties with regard to fatty acid oxidation in Morris hepatoma 5123C, compared with those in Becker H-252 and Morris hepatoma 7288CTC, may reflect the different extent of differentiation in these tumors, the former being a slow-growing, well-differentiated tumor, whereas the latter represent tumors that are less differentiated and of more rapid growth rate.

¹ These studies were supported in part by USPHS Grant AA00287.

² Recipient of Research Scientist Career Development Award 1 K02-AA00003-01 from the National Institute on Alcohol Abuse and Alcoholism.

Received 12/31/75. Accepted 5/14/76.