title: Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of xanthine oxidase (EC 1.2.3.2).
abstract: The behavior of the rate-limiting enzyme of purine catabolism, xanthine oxidase (EC 1.2.3.2); was examined in normal liver, in 17 hepatomas of different growth rates, and in rapidly growing differentiating and regenerating liver. Xanthine oxidase activity was measured in the supernatant fluid prepared by centrifugation of 5% homogenates at 100,000  X g for 30 min. There was no uricase activity in the supernatant fluid. The affinity of xanthine oxidase to xanthine was similar in normal liver and in slow- and rapidly growing hepatomas (Km=6 to 8 muM), and theoptimum pH was 8.0; at pH 7.4, the activity was 80% of that at the pH optimum. A standard assay was worked out for the liver and hepatoma systems; the enzyme activity was linear during 60-min incubation and proportionate with amounts of protein added over a range of 0.5 to 3.0 mg. Xanthine oxidase specific activity was 9 times higher in small intestine than in liver. Activities in lung, spleen, kidney, heart, testes, and thymus were 67, 59, 21, 19, 8, and 8%, and in skeletal muscle, brain, and bone marrow activities were 5% of that of the liver. In regenerating liver, xanthine oxidase activity was not changed from that of the liver of sham-operated controls up to 96 hr after operation. The activity of the average differentiating liver cell was less than 5% of that of adult liver during the first week after birth. At postnatal ages of 18, 25, 30 and 40 days, the activity rose to 18, 46, 76, and 94%, respectively, of that of the adult liver. In starvation, hepatic xanthine oxidase activity per cell was preferentially depleted as compared to the decline in protein concentration. Upon refeeding, the enzymatic activity was restored more slowly than the protein content. Since xanthine oxidase activity was decreased in all examined hepatomas, including the slowest-growing, well-differentiated neoplasms, the altered activity of this enzyme appears to be.linked with neoplastic transformatiobosyl 1-pyrophosphate amidotransferase (EC 2.4.2.14), was increassed in the hepatomas, the reprogramming of gene expression results in an imbalance that favors the synthetic over the catabolic potential. This enzymatic imbalance should confer selective advantages to the cancer cells.
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D005260:Female; D005796:Genes; D007421:Intestine, Small / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011687:Purines / Q000378:metabolism*; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D013217:Starvation / Q000201:enzymology; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D011687:Purines; D014969:Xanthine Oxidase