Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbamoyl-phosphate synthase II (glutamine-hydrolyzing) (EC 6.3.5.5) (synthase II) is the first and rate-limiting enzyme in the de novo UTP biosynthetic pathway. Leucine pulse-labeling in the rat demonstrated that in the rapidly proliferating hepatoma 3924A the ratio of radioactivity of synthase II to that of total cytosolic protein was 168.2 +/- 11.0 (SE) X 10(-3). This synthetic rate for the tumor enzyme was 9.7-fold higher than that for the liver synthase II, 17.4 +/- 4.0 X 10(-3). Since the degradation rate for hepatoma 3924A enzyme (t1/2 = 65.5 h) was similar to the rate for liver synthase II (t1/2 = 69.3 h), the increase in tumor synthase II activity and amount was due primarily to an elevation in enzyme synthesis in the presence of an unaltered catabolic rate. The results indicate that the reprogramming of gene expression in the hepatoma entails an increased production rate of the rate-limiting enzyme of UTP synthesis. This increase in the activity, concentration, and synthesis of tumor synthase II should provide a heightened capacity for the de novo pyrimidine biosynthetic pathway, thus conferring a selective advantage to the cancer cells.
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PMID:Increased synthesis of carbamoyl-phosphate synthase II (EC 6.3.5.5) in hepatoma 3924A. 351 20

In rat livers and hepatomas, carbamoyl phosphate synthetase (glutamine-hydrolyzing) (EC 6.3.5.5) (synthetase II), the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, was separated from carbamoyl phosphate synthetase (ammonia) (EC 6.3.4.16) (synthetase I) ammonium sulfate and hydroxylapatite fractionations and gel filtration on Sephadex G-25. Both liver and hepatoma 3924A synthetase II activities were subject to feedback inhibition by UTP and to stimulation by 5-phosphoribosyl 1-pyrophosphate. UTP (0.5 mM) enhanced the apparent Km for MgATP from 2.3 to 7.6 mM, whereas 0.1 mM 5-phosphoribosyl 1-pyrophosphate reduced it to 0.5 mM. At 2 mM MgATP, 3 or 7 microM 5-phosphoribosyl 1-pyrophosphate yielded half-maximal activation (Ka) in the absence or presence of 0.5 mM UTP; UTP altered the stimulation kinetics from hyperbolic to sigmoidal. In the rat, synthetase II activities were highest in thymus, testis and spleen. In differentiating and regenerating rat livers, activities were 2.2- and 1.5-fold higher than in adult livers. In 17 hepatomas of different growth rates, synthetase II activity increased 1.3- to 9.5-fold over liver values; the rise correlated positively with tumor growth rates. Synthetase II activities also increased in a kidney tumor (5.0-fold) and in a sarcoma (18.1-fold) in the rat and in a human colon tumor (3.3-fold).
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PMID:Regulatory properties and behavior of activity of carbamoyl phosphate synthetase II (glutamine-hydrolyzing) in normal and proliferating tissues. 705 79