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.

Arginase Deficiency Presenting as Cerebral Palsy

PEDIATRICS ◽  
1993 ◽  
Vol 91 (5) ◽  
pp. 995-996
Author(s):  
ANGELA E. SCHEUERLE ◽  
ROBERT MCVIE ◽  
ARTHUR L. BEAUDET ◽  
STUART K. SHAPIRA
Keyword(s):  
Cerebral Palsy ◽  
Autosomal Recessive ◽  
Urea Cycle ◽  
Case Reports ◽  
Growth Failure ◽  
Autosomal Recessive Disorder ◽  
Psychomotor Retardation ◽  
Uncomplicated Pregnancy ◽  
Arginase Deficiency ◽  
Cycle Disorders

Arginase catalyzes the conversion of arginine to ornithine and urea in the final step of the urea cycle. The enzyme deficiency disease, argininemia, is a rare autosomal recessive disorder which presents with progressive psychomotor retardation, growth failure, seizures, and spasticity affecting the lower extremities more than the upper.1 It does not, however, commonly have the severe hyperammonemia seen with other urea cycle disorders.1,2 We describe two unrelated patients, previously thought to have cerebral palsy, who were later found to have arginase deficiency. This suggests that the condition may be underdiagnosed because of its relatively mild symptoms. CASE REPORTS Patient 1, a 9-year-old boy, was born at term after an uncomplicated pregnancy to nonconsanguineous African-American parents.

Beta-ketothiolase deficiency brought with lethargy: Case report

2011 ◽  
Vol 30 (10) ◽  
pp. 1724-1727 ◽  
Author(s):  
Vefik Arica ◽  
Secil Gunher Arica ◽  
Huseyin Dag ◽  
Hatice Onur ◽  
Ömer Obut ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Case Report ◽  
Blood Glucose ◽  
Amino Acid ◽  
Ketone Body ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Branched Chain Amino Acid ◽  
Amino Acid Levels ◽  
Branched Chain

Beta-ketothiolase deficiency is a rare autosomal recessive disorder of isoleucine and ketone body metabolism. This disorder is clinically characterized by ketoacidotic attacks. Ketoacidosis, vomiting, and dehydration, lethargy and coma may be seen during attacks. A 9-month-old girl was admitted to our hospital with acidosis and dehydration. The patient was lethargic. Ketoacidosis was suspected because of acetone odor on her breath. Her blood glucose level was 262 mg/dL and urine ketone was (++++). Branched chain amino acid levels were elevated in her blood sample. Organic acid analysis of urine revealed 2-methylacetoacetyl-CoA thiolase deficiency. This was reported because of rarity of the disease and we should consider it in the differential diagnosis of ketoacidotic episodes.

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".

scholarly journals Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Danilo Giorgi Abranches de Andrade ◽  
Roberta Martins Basso ◽  
Angelo José Magro ◽  
Renée Laufer-Amorim ◽  
Alexandre Secorun Borges ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Dwarf Phenotype ◽  
Horse Genome ◽  
Complex Interactions ◽  
New Variant ◽  
Exon 11

Abstract Chondrodysplastic dwarfism in Miniature horses is an autosomal recessive disorder previously associated with four mutations (D1, D2, D3*, and D4) in the aggrecan (ACAN) gene. The aim of this study was to identify additional variants in the candidate ACAN gene associated with chondrodysplastic dwarfism in Miniature horses. Fifteen dwarf Miniature horses were found to possess only one of the dwarfism-causing variants, and two possessed none of the variants. The ACAN exons (EquCab3.0) of seven dwarf Miniature horses were sequenced. A missense SNP in coding exon 11 (g.95271115A > T, c.6465A > T—RefSeq XM_005602799.2), which resulted in the amino acid substitution p.Leu2155Phe (RefSeq XP_005602856.2), was initially associated with the dwarf phenotype. The variant was tested and found present in 14 dwarf foals as well as one parent of each, and both parents of a dwarf possessing two copies. Genetic testing of 347 phenotypically normal Miniature horses demonstrated that none had more than one of the dwarf alleles or c.6465A > T. However, a study of large breeds revealed the presence of c.6465A > T, which was present in homozygosis in two Mangalarga Marchador horses. We suggest that c.6465A > T as a marker of disequilibrium or complex interactions in the Miniature horse genome could contribute to the associated dwarfism.

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.

Genetic Analysis of Afibrinogenemia and Hypofibrinogenemia: Novel Mutations in the FGB Gene in the Turkish Population

2020 ◽  
Vol 143 (6) ◽  
pp. 529-532
Author(s):  
Didem Torun  Özkan ◽  
Nazan Sarper ◽  
Nejat Akar
Keyword(s):  
Amino Acid ◽  
Autosomal Recessive ◽  
Adenine Nucleotide ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Turkish Population ◽  
Chain Gene ◽  
Congenital Afibrinogenemia ◽  
Low Levels ◽  
First Time

<b><i>Introduction:</i></b> Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels &#x3c;1.5 g/L. <b><i>Objective:</i></b> In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. <b><i>Methods:</i></b> We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the <i>FGB</i> gene using the DNA isolated from the peripheral blood samples of patients and controls. <b><i>Results and Conclusion:</i></b> We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same patient of Turkish descent. Furthermore, there was a novel heterozygous guanine-to-adenine nucleotide change in exon 3. This caused the change of arginine amino acid to threonine amino acid at position 136 (p.A136T) in a protein, which has not been described in the literature before.

scholarly journals Is there any relationship between mutation in CPS1 Gene and pregnancy loss?

2019 ◽  
Author(s):  
Mehrdad Talebi ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Kambiz Kalhor ◽  
Mohammadreza Dehghani
Keyword(s):  
Newborn Infant ◽  
Pregnancy Loss ◽  
Autosomal Recessive ◽  
Urea Cycle ◽  
Hereditary Disease ◽  
The Other ◽  
Carbamoyl Phosphate Synthetase ◽  
Specific Enzyme ◽  
Carbamoyl Phosphate ◽  
Carbamoyl Phosphate Synthetase 1

Background: Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific enzyme with the lowest enzymatic rate, which determines the overall rate of the other reactions in the pathway that converts ammonia to carbamoyl phosphate in the first step of the urea cycle. Carbamoyl phosphate synthetase 1 deficiency (CPS1D), which usually presents as lethal hyperammonemia, is a rare autosomal recessive hereditary disease. Case: We report a case of a two-day-old female neonate with lethal hyperammonemia. The newborn infant was presented with hyperammonemia (34.7

VARIATION WITH AGE OF THE ENZYMES OF THE UREA CYCLE AND ASPARTATE TRANSCARBAMYLASE IN RAT LIVER

1967 ◽  
Vol 45 (9) ◽  
pp. 1427-1432 ◽  
Author(s):  
R. Charbonneau ◽  
A. Roberge ◽  
L. Berlinguet
Keyword(s):  
Urea Cycle ◽  
Protein Biosynthesis ◽  
Adult Life ◽  
Limiting Factor ◽  
Argininosuccinate Synthetase ◽  
Aspartate Transcarbamylase ◽  
Carbamyl Phosphate ◽  
Carbamyl Phosphate Synthetase ◽  
Metabolic Activities ◽  
Very High

The activities of aspartate transcarbamylase and of five enzymes involved in the urea cycle were determined in the liver of rats from the embryonic state to adulthood. Aspartate transcarbamylase activity is very high in the embryo and at birth. It remains high until the rat reaches a body weight of 50 g, after which there is a rapid decrease which levels off to a plateau at adulthood. The enzymatic activities of carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinase, and arginase are very low at the embryonic stage. The activity of these enzymes increases gradually with age until a plateau is reached, except for argininosuccinase which also increases in young animals but decreases in adult life. Of these enzymes, argininosuccinate synthetase always has the lowest activity and seems to be the limiting factor in the synthesis of urea. These results indicate that the biosynthesis of pyrimidines and urea vary inversely at different ages that correspond to different metabolic activities of the animals. Thus, an inverse relation is established between the two pathways from carbamyl phosphate, leading to protein biosynthesis (formation of RNA from orotic acid) and to protein catabolism (formation of urea).

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