Enzymes of salvage and de novo pathways of synthesis of pyrimidine nucleotides in human colorectal adenocarcinomas

Abstract

The activity of uridine-cytidine kinase (Urd-Cyd kinase). a key enzyme in the salvage of pyrimidine nucleosides, averaged 0.86 +/- 0.16 (S.E.M.) nmole uridine phosphates . min-1 . (mg protein)-1 in fifty-three specimens of human colorectal adenocarcinomas. The activity of fluorouracil phosphoribosyltransferase (FUPRTase) in thirty-five carcinoma specimens averaged only 0.19 +/- 0.07 nmole fluorouridine phosphates . min-1 . (mg protein)-1. The activity of the last enzyme in the de novo pathway of biosynthesis of UMP, i.e. orotidine 5'-monophosphate (OMP) decarboxylase, averaged 0.21 +/- 0.04 nmole CO2 . min-1 . (mg protein)-1. The activity of Urd-Cyd kinase was increased approximately 2.3-fold, and that of OMP decarboxylase by about 91%, while that of FUPRTase was increased by only 27%, as compared to that of normal human colonic mucosa. Of the colorectal carcinomas studied, 72% were moderately differentiated, 21% poorly differentiated, and 7% well differentiated. The mean diameter of the fifty-three carcinomas was 5.5 cm, and pathologic staging led to classification of 15% as Dukes' A, 36% as Dukes' B, 47% as Dukes' C, and 2% as carcinoma in situ. No correlations between the level of the enzyme activities studied and any pathologic characteristics of the carcinomas could be discerned.