Document Detail


Regulatory properties and behavior of activity of carbamoyl phosphate synthetase II (glutamine-hydrolyzing) in normal and proliferating tissues.
MedLine Citation:
PMID:  7053379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
T Aoki; H P Morris; G Weber
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  257     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1982 Jan 
Date Detail:
Created Date:  1982-02-25     Completed Date:  1982-02-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  432-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / isolation & purification,  metabolism*
Colonic Neoplasms / enzymology
Glutamine / pharmacology
Humans
Hydrogen-Ion Concentration
Kidney Neoplasms / enzymology
Kinetics
Ligases / metabolism*
Liver / enzymology*
Liver Neoplasms, Experimental / enzymology*
Male
Neoplasms, Experimental / enzymology
Rats
Rats, Inbred ACI
Ribonucleotides / pharmacology
Grant Support
ID/Acronym/Agency:
CA-05034/CA/NCI NIH HHS; CA-10729/CA/NCI NIH HHS; CA-13526/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Ribonucleotides; 56-85-9/Glutamine; EC 6.-/Ligases; EC 6.3.5.5/Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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