Biosynthesis and Utilization of Acetyl Phosphate, Formyl Phosphate, and Carbamyl Phosphate and their Relations to the Urea Cycle

1964 ◽  
pp. 128-149 ◽  
Author(s):  
SANTIAGO GRISOLIA ◽  
LUISA RAIJMAN
Keyword(s):  
Urea Cycle ◽  
Acetyl Phosphate ◽  
Carbamyl Phosphate

scholarly journals N-Acetylglutamate and its changing role through evolution

2003 ◽  
Vol 372 (2) ◽  
pp. 279-290 ◽  
Author(s):  
Ljubica CALDOVIC ◽  
Mendel TUCHMAN
Keyword(s):  
Amino Acid ◽  
Autosomal Recessive ◽  
Urea Cycle ◽  
Evolutionary Relationship ◽  
Autosomal Recessive Disorder ◽  
The Other ◽  
Arginine Biosynthesis ◽  
Carbamyl Phosphate ◽  
Carbamyl Phosphate Synthetase ◽  
Changing Role

N-Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by l-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined. In humans, inherited NAGS deficiency is an autosomal recessive disorder causing hyperammonaemia and a phenotype similar to CPSI deficiency. Several mutations have been recently identified in the NAGS genes of families affected with this disorder.

Inhibition of urea cycle enzymes by aspartic acid analogues

1969 ◽  
Vol 47 (3) ◽  
pp. 361-369
Author(s):  
S. M. Bayer ◽  
W. C. McMurray
Keyword(s):  
Aspartic Acid ◽  
Energy Production ◽  
Urea Cycle ◽  
Argininosuccinate Synthetase ◽  
Substrate Type ◽  
Carbamyl Phosphate ◽  
Enzyme Preparations ◽  
Carbamyl Phosphate Synthetase ◽  
Liver Homogenates

The inhibition of urea biosynthesis by analogues of aspartic acid was studied in vitro in homogenates and enzyme preparations from rat liver. Each of the analogues tested inhibited the overall utilization of citrulline for urea formation by liver homogenates. The concentrations required to give 50% inhibition were: N-allylaspartate, 0.248 M; α-methylaspartate, 0.140 M; β-methylaspartate, 0.078 M; and β-hydroxy-β-methylaspartate, 0.038 M. The β-substituted analogues partly replaced aspartate as a substrate for citrulline utilization in liver homogenates. The replacement was probably due to transamination of the analogues with oxaloacetate, since the effect was not observed when the assay mixture did not contain a substrate which could yield oxaloacetate.A study of individual enzymes of the urea cycle showed that arginase, argininosuccinase, and ornithine transcarbamylase were not greatly affected by the analogues. However, carbamyl phosphate synthetase as well as argininosuccinate synthetase were strongly inhibited, suggesting that the analogues act by some mechanism other than simple antagonism of aspartate. Part of the inhibition was related to the ability of the analogues to complex Mg2+, since increased concentrations of Mg2+ prevented the inhibition of carbamyl phosphate synthetase and reduced the inhibition of argininosuccinate synthetase by α-methylaspartate and N-allylaspartate. In addition, β-methylaspartate was found to depress oxidative and phosphorylative reactions, thus interfering with the energy production required for urea formation.Aspartic acid in concentrations comparable with those required to effect inhibition by α-methylaspartate produced a marked inhibition of citrulline utilization in liver homogenates and of purified argininosuccinate synthetase. This observation suggests that part of the inhibitions observed with the analogues are of the "substrate type".

Carbamyl phosphate synthetase in the chick

1969 ◽  
Vol 47 (1) ◽  
pp. 61-63 ◽  
Author(s):  
Charles G. Maresh ◽  
Theodore H. Kwan ◽  
Sumner M. Kalman
Keyword(s):  
Enzyme Activity ◽  
Chick Embryo ◽  
Urea Cycle ◽  
Mitochondrial Fraction ◽  
Pyrimidine Biosynthesis ◽  
Developmental Pattern ◽  
Synthetase Activity ◽  
Young Chick ◽  
Carbamyl Phosphate ◽  
Carbamyl Phosphate Synthetase

Carbamyl phosphate synthetase activity is present in the liver of the chick embryo and in the young chick. This enzyme activity is not dependent upon acetylglutamate and is not present in the mitochondrial fraction. Because the urea cycle is not present in chick liver and because of the developmental pattern of the enzyme activity, we infer that this enzyme is involved in pyrimidine biosynthesis.

VARIATION OF THE ENZYMES OF THE UREA CYCLE AND ASPARTATE TRANSCARBAMYLASE IN LIVER OF PREGNANT RATS

1967 ◽  
Vol 45 (9) ◽  
pp. 1371-1374 ◽  
Author(s):  
A. Roberge ◽  
R. Charbonneau ◽  
L. Berlinguet
Keyword(s):  
Orotic Acid ◽  
Urea Cycle ◽  
Female Rats ◽  
Male Rats ◽  
Urea Synthesis ◽  
Aspartate Transcarbamylase ◽  
Carbamyl Phosphate ◽  
Pregnant Rats ◽  
Specific Activities ◽  
In Pregnancy

The variations in the specific activities of the enzymes of the urea cycle were studied in the livers of pregnant rats and also in the livers of male rats and other females with the same body weight. The specific activities of the five enzymes of the urea cycle are the same in male and in female except for argininosuccinase. The activity of this enzyme is twice as high in female rats as in male rats. In pregnancy, the activities of the enzymes of the urea cycle are decreased except for arginase, which increases. Aspartate transcarbamylase remains constant during the same period.These results lead to the supposition that another pathway for the synthesis of orotic acid may exist, or more probably that there exist two carbamyl phosphate synthetases, one for pyrimidine biosynthesis and one for urea synthesis.

L-Arginine, the Sickling Phenomenon, and Cystic Fibrosis

PEDIATRICS ◽  
1972 ◽  
Vol 49 (6) ◽  
pp. 933-933
Author(s):  
C. Solomons ◽  
W. Hathaway ◽  
E. Cotton
Keyword(s):  
Cystic Fibrosis ◽  
Protein Structure ◽  
Urea Cycle ◽  
Clinical Effects ◽  
Carbamyl Phosphate ◽  
Low Toxicity ◽  
Chemical Groups

The action of urea in stabilizing s-hemoglobin is thought to be due to its ability to alter the conformation of proteins. Compounds such as guanidine and arginine, which also possess chemical groups capable of altering protein structure, have been alluded to as logically possible alternatives or adjuncts to the use of urea. Neutralized L-Arginine is particularly attractive because of its low toxicity and well known clinical effects. In addition, arginine is thought to stimulate the urea cycle: an intermediate of this cycle, carbamyl phosphate, has recently been shown to reduce sickling.

Sign in / Sign up

Export Citation Format

Share Document