Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas

J. E. Denton, M. S. Lui, T. Aoki, John Eble, E. Takeda, J. N. Eble, J. L. Glover, G. Weber

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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-phosphate synthetase II, cytidine 5'-triphosphate synthetase, orotidine 5'-monophosphate decarboxylase, and aspartate carbamoyltransferase (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, carbamoyl-phosphate synthetase II, aspartate carbamoyltransferase, 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 tumos were in between those of the slow and the rapidly growing xenografts, forming a gradient toward the profound biochemical imbalance of the rapidly growing colon carcinoma xenograft. Because of the different growth rates and enzymology of these model systems, the applicability of chemotherapeutic results from mouse tumors and human xenografts requires cautious interpretation regarding the possible predictive power of the drug responsiveness of human colon tumors. The concurrent increase of activities of key enzymes of de novo and salvage pathways of pyrimidine biosynthesis suggests that a successful anticancer chemotherapy requires inhibitors of strategic enzymes of both pathways.

Original languageEnglish (US)
Pages (from-to)1176-1183
Number of pages8
JournalCancer Research
Volume42
Issue number3
StatePublished - 1982
Externally publishedYes

Fingerprint

Carbohydrate Metabolism
Colon
Carcinoma
Neoplasms
Heterografts
Mucous Membrane
CTP synthetase
Pentoses
Enzymes
Galactokinase
Aspartate Carbamoyltransferase
Deoxycytidine Kinase
Carbamyl Phosphate
Phosphates
pyrimidine
Ligases
Human Activities
Uridine Phosphorylase
Uridine Kinase
Carboxy-Lyases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Denton, J. E., Lui, M. S., Aoki, T., Eble, J., Takeda, E., Eble, J. N., ... Weber, G. (1982). Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas. Cancer Research, 42(3), 1176-1183.

Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas. / Denton, J. E.; Lui, M. S.; Aoki, T.; Eble, John; Takeda, E.; Eble, J. N.; Glover, J. L.; Weber, G.

In: Cancer Research, Vol. 42, No. 3, 1982, p. 1176-1183.

Research output: Contribution to journalArticle

Denton, JE, Lui, MS, Aoki, T, Eble, J, Takeda, E, Eble, JN, Glover, JL & Weber, G 1982, 'Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas', Cancer Research, vol. 42, no. 3, pp. 1176-1183.
Denton JE, Lui MS, Aoki T, Eble J, Takeda E, Eble JN et al. Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas. Cancer Research. 1982;42(3):1176-1183.
Denton, J. E. ; Lui, M. S. ; Aoki, T. ; Eble, John ; Takeda, E. ; Eble, J. N. ; Glover, J. L. ; Weber, G. / Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas. In: Cancer Research. 1982 ; Vol. 42, No. 3. pp. 1176-1183.
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