Abstract 2334: Discovery of selective inhibitors of carbamoyl phosphate synthetase I (CPS1) to modulate cancer relevant metabolic pathways

2021 ◽  
Author(s):  
Shihua Yao ◽  
Tuong-Vi Nguyen ◽  
Alan Rolfe ◽  
Anant A. Agrawal ◽  
Jiyuan Ke ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Carbamoyl Phosphate Synthetase ◽  
Selective Inhibitors ◽  
Carbamoyl Phosphate

scholarly journals Product inhibition studies on bovine liver carbamoyl phosphate synthetase

1974 ◽  
Vol 141 (3) ◽  
pp. 817-824 ◽  
Author(s):  
Keith R. F. Elliott ◽  
Keith F. Tipton
Keyword(s):  
Inorganic Phosphate ◽  
Substrate Binding ◽  
Inorganic Ions ◽  
Bovine Liver ◽  
Product Inhibition ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Product Release ◽  
Proposed Model ◽  
Inhibition Studies

A study of the product-inhibition patterns of carbamoyl phosphate synthetase from bovine liver is reported. Inhibition by adenosine, AMP and inorganic ions is also reported. The results are in agreement with the previously proposed model in which the order of substrate binding is ATPMg, followed by HCO3−, ATPMg and NH4+. The order of product release on the basis of the reported results is carbamoyl phosphate, followed by ADPMg, ADPMg and inorganic phosphate.

Inactivation by acivicin of carbamoyl-phosphate synthetase II of human colon carcinoma

1985 ◽  
Vol 34 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Judith S. Sebolt ◽  
Takashi Aoki ◽  
John N. Eble ◽  
John L Glover ◽  
George Weber
Keyword(s):  
Colon Carcinoma ◽  
Human Colon ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Human Colon Carcinoma

Spatial relationships among the active and allosteric sites of carbamoyl-phosphate synthetase

1985 ◽  
Vol 13 (2) ◽  
pp. 98-109 ◽  
Author(s):  
Philip G. Kasprzyk ◽  
Eric Whalen-Pederson ◽  
Paul M. Anderson ◽  
Joseph J. Villafranca
Keyword(s):  
Spatial Relationships ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Allosteric Sites

scholarly journals Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion

2004 ◽  
Vol 287 (2) ◽  
pp. G344-G351 ◽  
Author(s):  
Béatrice Mouillé ◽  
Véronique Robert ◽  
François Blachier
Keyword(s):  
Cell Metabolism ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Ammonia Metabolism ◽  
Ornithine Carbamoyl Transferase ◽  
Urea Production ◽  
Colonic Lumen ◽  
Isocaloric Diets ◽  
The One

Chronic high-protein consumption leads to increased concentrations of NH4+/NH3 in the colon lumen. We asked whether this increase has consequences on colonic epithelial cell metabolism. Rats were fed isocaloric diets containing 20 (P20) or 58% (P58) casein as the protein source for 7 days. NH4+/NH3 concentration in the colonic lumen and in the colonic vein blood as well as ammonia metabolism by isolated surface colonic epithelial cells was determined. After 2 days of consumption of the P58 diet, marked increases of luminal and colonic vein blood NH4+/NH3 concentrations were recorded when compared with the values obtained in the P20 group. Colonocytes recovered from the P58 group were characterized at that time and thereafter by an increased capacity for l-ornithine and urea production through arginase ( P < 0.05). l-Ornithine was mostly used in the presence of NH4Cl for the synthesis of the metabolic end product l-citrulline. After 7 days of the P58 diet consumption, however, the ammonia metabolism into l-citrulline was found lower ( P < 0.01) when compared with the values measured in the colonocytes recovered from the P20 group despite any decrease in the related enzymatic activities (i.e., carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase). This decrease was found to coincide with a return of blood NH4+/NH3 concentration in colonic portal blood to values close to the one recorded in the P20 group. In response to increased NH4+/NH3 concentration in the colon, the increased capacity of the colonocytes to synthesize l-ornithine is likely to correspond to an elevated l-ornithine requirement for the elimination of excessive blood ammonia in the liver urea cycle. Moreover, in the presence of NH4Cl, colonocytes diminished their synthesis capacity of l-citrulline from l-ornithine, allowing a lower cellular utilization of this latter amino acid. These results are discussed in relationship with an adaptative process that would be related to both interorgan metabolism and to the role of the colonic epithelium as a first line of defense toward luminal NH4+/NH3 concentrations.

scholarly journals Acute effects of glucagon on citrulline biosynthesis

1982 ◽  
Vol 206 (3) ◽  
pp. 627-631 ◽  
Author(s):  
D Rabier ◽  
P Briand ◽  
F Petit ◽  
P Parvy ◽  
P Kamoun ◽  
...  
Keyword(s):  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Carbamoyl Phosphate Synthetase ◽  
Acute Effects ◽  
Carbamoyl Phosphate ◽  
Carbohydrate Diet ◽  
Acetylglutamate Synthase

Mitochondria isolated from livers of rats fed on different diets showed altered capacity to synthesize citrulline. Glucagon, 15 min after injection, increases citrulline biosynthesis, except after the high-protein diet. A significant correlation between citrulline biosynthesis and N-acetylglutamate content with and without glucagon treatment was shown when rats were fed on a standard or a carbohydrate diet. Different diets modified carbamoyl phosphate synthetase I (EC 6.3.4.16) and N-acetylglutamate synthase (acetyl-CoA:L-glutamate N-acetyltransferase, EC 2.3.1.1) activities. Glucagon did not modify these activities.

Sign in / Sign up

Export Citation Format

Share Document