Disease relevance of aldicarb

• Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome [1].
• Twelve episodes of hyperammonemia in seven children deficient in carbamyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase were treated; one patient died and the others recovered [2].
• In addition, a major mitochondrial enzyme present in normal liver, carbamyl phosphate synthetase, was missing or greatly reduced in the slow-growing, highly differentiated hepatoma 9618A, a tumor that is considered to be similar to normal liver in many biochemical and morphological respects [3].
• Carbamyl phosphate synthetases in rat liver neoplasms [4].
• Identification of the regulatory domain of the mammalian multifunctional protein CAD by the construction of an Escherichia coli hamster hybrid carbamyl-phosphate synthetase [5].

Psychiatry related information on aldicarb

• In the presence of 20 mM carbamyl phosphate, 93% of the activity is retained during a 1-h reaction time [6].

High impact information on aldicarb

• Carbamyl phosphate synthetase I (CPS I; EC6,3,4,16) is an autosomal recessive disorder characterized by hyperammonemia [7].
• The role of arginine as an essential amino was evaluated in four children with one of the deficiencies of carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, and argininosuccinase [8].
• Phosphorylation activates the ammonia-dependent carbamyl phosphate synthetase activity of the complex by reducing the apparent Km for ATP [9].
• These results indicate that carbamyl phosphate synthetase I is synthesized as a polypeptide that is indistinguishable from the mature enzyme by the analytical methods used and that it is not grossly modified during its transport into mitochondria [10].
• Functional arginyl residues as ATP binding sites of glutamine synthetase and carbamyl phosphate synthetase [11].

Chemical compound and disease context of aldicarb

• A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 microM, associated with valproate (VPA) treatment [12].
• Escherichia coli carbamyl-phosphate synthetase (CPSase), a monofunctional protein consisting of amido-transferase and synthetase subunits, is allosterically inhibited by UMP and activated by NH3, IMP, and ornithine [5].
• Application of the pulse-chase procedure to study of the binding and utilization of ATP by glutamine-dependent carbamyl phosphate synthetase from Escherichia coli showed that the enzyme binds the two molecules of ATP used in this reaction at the same time, and that the two ATP-binding sites are functionally different [13].
• The amidotransferase or glutaminase (GLNase) domain of mammalian carbamyl phosphate synthetase (CPSase), part of a 243-kDa polypeptide that initiates de novo pyrimidine biosynthesis, has been cloned and expressed in Escherichia coli [14].
• Carbamyl phosphate synthetase from Escherichia coli has been shown to use only the A isomer of adenosine-5'-[2-thiotriphosphate] in both the ATPase reaction (MgATP HCO3- leads to MgADP + Pi) and the carbamyl phosphate synthesis reaction (2MgATP + HCO3- + L-glutamine leads to 2MgADP + Pi + carbamyl-P + L-glutamate) [15].

Biological context of aldicarb

• We have identified an essential cis element in the proximal promoter region of the rat carbamyl phosphate synthetase I (CPSI) gene that is requisite for promoter activity in liver nuclear extracts [16].
• Mitochondrial ultrastructure was also essentially normal in the heterozygotes for carbamyl phosphate synthetase I deficiency [17].
• In parabiotic animals, carbamyl phosphate synthetase activity and urea synthesis were lowered in the host livers of partners bearing tumors with high carbamyl phosphate synthetase- and urea-synthetic activity, but there was no significant effect on urea cycle activity in the normal partners [18].
• Sequence of the small subunit of yeast carbamyl phosphate synthetase and identification of its catalytic domain [19].
• The amidotransferase or glutaminase domain (GLN domain) of mammalian carbamyl-phosphate synthetase II (CPSase II) catalyzes glutamine hydrolysis and transfers ammonia to the synthetase domain (CPS domain), where carbamyl phosphate formation is catalyzed in three consecutive reactions [20].

Anatomical context of aldicarb

• Carbamyl-phosphate synthetase I is a cell-type specific enzyme, being expressed only in hepatocytes and epithelial cells of the intestinal mucosa [21].
• A simple and rapid procedure is described for purification of carbamyl phosphate synthetase from the matrix fraction of rat liver mitochondria [22].
• No such activity was observed, however, in extracts from HeLa, a cell line which does not express carbamyl-phosphate synthetase I [21].
• Glucose is the primary stimulus for insulin secretion by pancreatic beta-cells, and it triggers membrane depolarization and influx of extracellular Ca2+ [23].
• Using the human cDNA clones, the human carbamyl phosphate synthetase gene was mapped to chromosome 2 utilizing a panel of Chinese hamster X human somatic cell hybrids [24].

Associations of aldicarb with other chemical compounds

• It is also of interest that, with both glutamine synthetase and carbamyl phosphate synthetase, only a small portion of the total arginyl population of these enzymes reacted with phenylglyoxal [11].
• Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and argininosuccinic acid synthetase [25].
• The observed phenomenon of collateral sensitivity is associated with a significantly higher inhibition of the specific activity of carbamyl phosphate synthetase II, pyrimidine nucleoside kinases, adenine phosphoribosyl transferase, and hypoxanthine phosphoribosyl transferase in the PALA-sensitive line, P388/ACIA [26].
• Evidence for an exceptionally reactive arginyl residue at the binding site for carbamyl phosphate in bovine ornithine transcarbamylase [27].
• CAD, is a multidomain polypeptide, with a molecular weight of over 200,000, that has glutamine-dependent carbamyl-phosphate synthetase, aspartate transcarbamylase, and dihydroorotase activity as well as regulatory sites that bind UTP and 5-phosphoribosyl 1-pyrophosphate [28].

Gene context of aldicarb

• Arginine deprivation imposed by PALO also caused increased expression of CPA1 and CPA2, coding respectively for the small and large subunits of arginine-specific carbamyl-phosphate synthetase [29].
• The protein sequence data provide strong evidence that the carbamyl phosphate synthetase I gene of rat, the carAB gene of E. coli, and the CPA1 and CPA2 genes of yeast were derived from common ancestral genes [30].
• Proteolytically induced changes in the molecular form of the carbamyl phosphate synthetase-uracil-aspartate transcarbamylase complex coded for by the URA2 locus in Saccharomyces cerevisiae [31].
• The cDNA insert contained all of the coding region for the glutaminase (GLN) and carbamyl phosphate synthetase (CPS) domains but lacked a short amino-terminal segment [32].
• A construct was made in which the intergenic region between the contiguous carA and carB genes was deleted and the sequences encoding the carbamyl-phosphate synthetase subunits were fused in frame [33].

Analytical, diagnostic and therapeutic context of aldicarb

• Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency [25].
• Molecular cloning of cDNA for rat and human carbamyl phosphate synthetase I [24].
• This component co-migrated with carbamyl phosphate synthetase activity when mitochondrial proteins were separated by gel filtration or sucrose gradient centifugation [34].
• Maintaining rats for 5 days on a diet containing 60% casein augmented the relative amount of carbamyl phosphate synthetase mRNA by about 2-fold, while a protein-free diet resulted in reduced levels of the mRNA (about 50% compared to animals on a normal diet) [35].
• Carbamyl phosphate bound Tc-99m and achieved bone uptake in mice, rabbits, and a human volunteer [36].

References