Enzymology of Pyrimidine and Carbohydrate Metabolism in Human Colon Carcinomas

摘要: The purpose of this study was to elucidate the biochemistry human primary colon tumors and relate relevance enzymology chemically induced, transplantable mouse carcinoma xenografts that tumor. pyrimidine, carbohydrate, pentose phosphate, galactose metabolism 14 cases compared with mucosa from same patients. There a marked alteration in tumor distinguished it normal mucosa. In pyrimidine metabolism, there an increase specific activities enzymes both de novo biosynthesis [carbamoyl-phosphate synthetase II, cytidine 5′-triphosphate synthetase, orotidine 5′-monophosphate decarboxylase, aspartate carbamoyltransferase (3.2-, 3.1-, 1.7-, 3.2-fold)] those salvage pathway [deoxycytidine kinase, thymidine uridine-cytidine kinase (4.6-, 3.0-, 2.2-fold)]. By contrast, activity catabolic enzyme, uridine phosphorylase, decreased 64%. trend toward glycolysis phosphate production. Galactokinase increased 4-fold. most stringent linkage enzyme neoplasia observed for 100% examined (galactokinase, deoxycytidine carbamoyl-phosphate carbamoyltransferase, synthetase). A comparison experimental model systems revealed similar contrasting enzymic patterns. tumors, alterations were or more pronounced than carcinomas; consistent higher growth rate tumors. not elevated as mucosa, whereas above profile slowly growing xenograft well-defined between slow rapidly xenografts, forming gradient towards profound biochemical imbalance xenograft. Because different rates these systems, applicability chemotherapeutic results requires cautious interpretation regarding possible predictive power drug responsiveness concurrent key pathways suggests successful anticancer chemotherapy inhibitors strategic pathways.