Enzymology of Pyrimidine and Carbohydrate Metabolism in Human Colon Carcinomas

Joan E. Denton, May S. Lui, Judith Sebolt, John N. Eble, George Weber, Takashi Aoki, Eiji Takeda, John L. Glover

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The purpose of this study was to elucidate the biochemistry of human primary colon tumors and to relate the relevance of the enzymology of chemically induced, transplantable mouse tumors and human colon carcinoma xenografts to that of the human primary colon tumor. The enzymology of pyrimidine, carbohydrate, pentose phosphate, and galactose metabolism of 14 cases of primary colon tumors was compared with that of colon mucosa from the same patients. There was a marked alteration in the enzymology of the human colon tumor that distinguished it from that of the normal mucosa. In pyrimidine metabolism, there was an increase in the specific activities of the enzymes of both de novo biosynthesis [carbamoyl-phos-phate synthetase II, cytidine 5́-triphosphate synthetase, oroti-dine 5́-monophosphate decarboxylase, and aspartate carbam-oyltransferase (3.2-, 3.1-, 1.7-, and 3.2-fold)] and of those of the salvage pathway [deoxycytidine kinase, thymidine kinase, and uridine-cytidine kinase (4.6-, 3.0-, and 2.2-fold)]. By contrast, the activity of the catabolic enzyme, uridine phosphorylase, decreased to 64%. There was a trend toward an increase in activities of enzymes of glycolysis and of pentose phosphate production. Galactokinase activity was increased 4-fold. The most stringent linkage of enzyme activities in human colon neoplasia was observed for those increased in 100% of the examined cases (galactokinase, deoxycytidine kinase, car-bamoyl-phosphate synthetase II, aspartate carbamoyltransfer-ase, and cytidine 5’-triphosphate synthetase). A comparison of the human primary colon tumors and of the experimental model systems revealed both similar and contrasting enzymic patterns. In pyrimidine metabolism of mouse tumors, the alterations were similar or more pronounced than those in human colon carcinomas; this was consistent with the higher growth rate of mouse tumors. The activities of the pentose phosphate enzymes in the mouse tumor were not elevated as compared to activities of the normal mouse colon mucosa, whereas in the human tumors the activities were increased above those of human normal colon mucosa. The enzymic profile of the slowly growing human carcinoma xenograft was similar to that of the normal human colon mucosa. The well-defined enzymic alterations of the human primary colon tumors were in between those of the slow and the rapidly growing xenografts, forming a gradient towards the profound biochemical imbalance of the rapidly growing colon carcinoma xenograft.

Original languageEnglish (US)
Pages (from-to)1176-1183
Number of pages8
JournalCancer Research
Issue number3
StatePublished - Mar 1 1982
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Denton, J. E., Lui, M. S., Sebolt, J., Eble, J. N., Weber, G., Aoki, T., Takeda, E., & Glover, J. L. (1982). Enzymology of Pyrimidine and Carbohydrate Metabolism in Human Colon Carcinomas. Cancer Research, 42(3), 1176-1183.