Looking for online definition of carbamoyl-phosphate synthase 1, mitochondrial in the Medical Dictionary? carbamoyl-phosphate synthase 1, mitochondrial explanation free. What is carbamoyl-phosphate synthase 1, mitochondrial? Meaning of carbamoyl-phosphate synthase 1, mitochondrial medical term. What does carbamoyl-phosphate synthase 1, mitochondrial mean?
TY - JOUR. T1 - Mitochondrial import and processing of mutant human ornithine transcarbamylase precursors in cultured cells. AU - Isaya, G.. AU - Fenton, W. A.. AU - Hendrick, J. P.. AU - Furtak, K.. AU - Kalousek, F.. AU - Rosenberg, L. E.. PY - 1988/1/1. Y1 - 1988/1/1. UR - http://www.scopus.com/inward/record.url?scp=0023697403&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0023697403&partnerID=8YFLogxK. U2 - 10.1128/MCB.8.12.5150. DO - 10.1128/MCB.8.12.5150. M3 - Article. C2 - 3244350. AN - SCOPUS:0023697403. VL - 8. SP - 5150. EP - 5158. JO - Molecular and Cellular Biology. JF - Molecular and Cellular Biology. SN - 0270-7306. IS - 12. ER - ...
TY - JOUR. T1 - Effects of dietary glutamine supplementation on lung injury induced by lipopolysaccharide administration. AU - Hou, Yu-Chen. AU - Pai, Man Hui. AU - Chiu, Wan Chun. AU - Hu, Ya Mei. AU - Yeh, Sung Ling. PY - 2009/3. Y1 - 2009/3. N2 - Acute lung injury (ALI) is a critical syndrome associated with respiratory dysfunction, and neutrophils are considered to be central to the pathogenesis of ALI. This study investigated the effects of glutamine (Gln) on neutrophil recruitment in a model of lipopolysaccharide (LPS)-induced ALI. C57BL/6 mice were fed a standard diet either with casein as the nitrogen source or with 25% of total nitrogen replaced by Gln. After 10 days, intratracheal instillation of LPS was used to induce ALI. Mice were killed at 0, 6, 12, and 24 h after LPS administration (n = 10/group). Bronchoalveolar lavage fluid and lung tissues were collected for further analysis. The results showed that, compared with the control group, lipid peroxide levels in the lungs were ...
TY - JOUR. T1 - Long-term treatment of girls with ornithine transcarbamylase deficiency. AU - Maestri, Nancy E.. AU - Brusilow, Saul W.. AU - Clissold, David B.. AU - Bassett, Susan S.. PY - 1996/9/19. Y1 - 1996/9/19. N2 - Background: Ornithine transcarbamylase is an X-linked mitochondrial enzyme that catalyzes the synthesis of citrulline from carbamoyl phosphate and ornithine. A deficiency of this enzyme leads to hyperammonemia and hyperglutaminemia. In boys the disease is often fatal when its onset occurs during the neonatal period, but it is milder when onset occurs later in childhood. Heterozygous girls may be normal or may have episodes of hyperammonemic encephalopathy and decline in cognitive function. We report here on the long-term outcome in girls with ornithine transcarbamylase deficiency enrolled in studies of treatments designed to activate new pathways of waste-nitrogen excretion. Methods: We studied 32 girls (age, 1 to 17 years) with ornithine transcarbamylase deficiency who had at ...
Rat liver ornithine carbamoyltransferase appears to be located exclusively in the mitochondria; the activity that is found in the soluble fraction is indistinguishable from mitochondrial ornithine carbamoyltransferase by simple kinetic criteria, and seems to result from breakage of mitochondria during homogenization. Of several rat tissues studied, only the liver and the mucosa of small intestine contain significant amounts of ornithine carbamoyltransferase; the activity in intestinal mucosa is less than one thousandth of that in liver. Qualitatively, this distribution coincides with that of carbamoyl phosphate synthetase I and its cofactor, acetylglutamate. The rat liver contents of carbamoyl phosphate and ornithine were 0.1 and 0.15μmol/g wet wt. of tissue respectively. On the basis of these values, it is proposed that in vivo the ornithine carbamoyltransferase activity of liver may be much lower than its maximal activity in vitro might suggest.. ...
New treatments need to be developed for the significant human diseases of toxoplasmosis and malaria to circumvent problems with current treatments and drug resistance. Apicomplexan parasites causing these lethal diseases are deficient in pyrimidine salvage, suggesting that selective inhibition of de novo pyrimidine biosynthesis can lead to a severe loss of uridine 5'-monophosphate (UMP) and thymidine 5'-monophosphate (dTMP) pools, thereby inhibiting parasite RNA and DNA synthesis. Disruption of Toxoplasma gondii carbamoyl phosphate synthetase II (CPSII) induces a severe uracil auxotrophy with no detectable parasite replication in vitro and complete attenuation of virulence in mice. Here we show that a CPSII cDNA minigene efficiently complements the uracil auxotrophy of CPSII-deficient mutants, restoring parasite growth and virulence. Our complementation assays reveal that engineered mutations within, or proximal to, the catalytic triad of the N-terminal glutamine amidotransferase (GATase) domain ...
AAUCD : Urea cycle disorders (UCD) are a group of inherited disorders of nitrogen detoxification that result when any of the enzymes in the urea cycle (carbamoylphosphate synthetase I: CPS I; ornithine transcarbamylase: OTC; argininosuccinic acid synthetase; argininosuccinic acid lyase; arginase; or the cofactor producer, N-acetyl glutamate synthetase: NAGS), have deficient or reduced activity. The role of the urea cycle is to metabolize and clear waste nitrogen, and defects in any of the steps of the pathway can result in an accumulation of ammonia, which can be toxic to the nervous system. The urea cycle is also responsible for endogenous production of the amino acids citrulline, ornithine, and arginine. Infants with a complete urea cycle enzyme deficiency typically appear normal at birth, but present with in the neonatal period as ammonia levels rise with lethargy, seizures, hyper- or hypoventilation, and ultimately coma or death. Individuals with partial enzyme deficiency may present later in life,
TY - JOUR. T1 - Safety of glutamine-enriched parenteral nutrient solutions in humans. AU - Lowe, D. K.. AU - Benfell, K.. AU - Smith, R. J.. AU - Jacobs, D. O.. AU - Murawski, B.. AU - Ziegler, T. R.. AU - Wilmore, D. W.. PY - 1990. Y1 - 1990. N2 - To determine the safety of glutamine-enriched parenteral nutrition, seven normal volunteers were admitted to the Clinical Research Center for three 5-d study periods. The subjects received infusions of parenteral nutrients containing increasing doses of glutamine (0, 0.285, and 0.570 g·kg body wt-1·d-1) substituted for alanine and glycine. Each study period was preceded by ≥ 2 wk of normal food intake. The diets were isocaloric (1.2X estimated basal metabolic rate) and isonitrogenous (1.5 g protein·kg-1·d-1) with nonprotein calories given as dextrose (38%) and fat emulsion (62%). The diets were all well tolerated and there were no untoward effects. Plasma glutamine concentrations increased significantly with glutamine administration but ...
Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, which is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains).[2][3][6] CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia, which is in turn used by the large chain to synthesize carbamoyl phosphate. The small subunit has a 3-layer beta/beta/alpha structure, and is thought to be mobile in most proteins that carry it. The C-terminal domain of the small subunit of CPSase has glutamine amidotransferase activity. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the ...
The climbing perch, Anabas testudineus, inhabits large rivers, canals, stagnant water bodies, swamps and estuaries, where it can be confronted with aerial exposure during the dry season. This study aimed to examine nitrogen excretion and metabolism in this fish during 4 days of emersion. Contrary to previous reports, A. testudineus does not possess a functional hepatic ornithineurea cycle because no carbamoyl phosphate synthetase I or III activity was detected in its liver. It was ammonotelic in water, and did not detoxify ammonia through increased urea synthesis during the 4 days of emersion. Unlike many air-breathing fishes reported elsewhere, A. testudineus could uniquely excrete ammonia during emersion at a rate similar to or higher than that of the immersed control. In spite of the fact that emersion had no significant effect on the daily ammonia excretion rate, tissue ammonia content increased significantly in the experimental fish. Thus, it can be concluded that 4 days of emersion caused ...
TY - JOUR. T1 - Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. T2 - A randomized, double-blind, controlled study. AU - Ziegler, Thomas R.. AU - Young, Lorraine S.. AU - Benfell, Kathleen. AU - Scheltinga, Marc. AU - Hortos, Kari. AU - Bye, Rancy. AU - Morrow, Frank D.. AU - Jacobs, Danny O.. AU - Smith, Robert J.. AU - Antin, Joseph H.. AU - Wilmore, Douglas W.. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 1992/5. Y1 - 1992/5. N2 - Objective: To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation. Design: Double-blind, randomized, controlled clinical trial. Setting: University teaching hospital. Patients: Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies. Intervention: Parenteral nutrition was initiated the day after ...
CTP synthase catalyses the ATP-dependent formation of CTP from UTP using either NH3 or l-glutamine as the nitrogen source. GTP is required as an allosteric effector to promote glutamine hydrolysis. In an attempt to identify nucleotide-binding sites, scanning alanine mutagenesis was conducted on a highly conserved region of amino acid sequence (residues 102-118) within the synthase domain of Escherichia coli CTP synthase. Mutant K102A CTP synthase exhibited wild-type activity with respect to NH3 and glutamine; however, the R105A, D107A, L109A and G110A enzymes exhibited wild-type NH3-dependent activity and affinity for glutamine, but impaired glutamine-dependent CTP formation. The E103A, R104A and H118A enzymes exhibited no glutamine-dependent activity and were only partially active with NH3. Although these observations were compatible with impaired activation by GTP, the apparent affinity of the D107A, L109A and G110A enzymes for GTP was reduced only 2-4-fold, suggesting that these residues do ...
TY - JOUR. T1 - Effect of Uridine on Response of 5-Azacytidine-resistant Human Leukemic Cells to Inhibitors of de Novo Pyrimidine Synthesis. AU - Grant, S.. AU - Bhalla, K.. AU - Gleyzer, M.. PY - 1984/12/1. Y1 - 1984/12/1. N2 - A uridine-cytidine kinase-deficient human promyelocytic leukemic subline (HL-60-5-aza-Cyd) has been isolated which is highly resistant to the antileukemic agent 5-azacytidine. Resistant cells exposed to 10-5 M 5-azacytidine for 2 hr exhibit a marked reduction in both the total intracellular accumulation of 5-azacytidine (11.9 versus 156.0 pmol/106 cells) as well as its incorporation into RNA (3.1 versus 43.4 pmol/μg D-ribose) compared to the parent line. These biochemical changes are associated with nearly a 100-fold decrease in sensitivity to the growth inhibitory effects of 5-azacytidine (concentration of drug associated with a 50% reduction in cell growth, 3.5 x 10-5 versus 5.0 x 10-7 M). 5-Azacytidine-resistant cells exhibit cross-resistance to 3-deazauridine, ...
TY - JOUR. T1 - Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducing myo-inositol biosynthesis. AU - Gardell, Alison M.. AU - Yang, Jun. AU - Sacchi, Romina. AU - Fangue, Nann A.. AU - Hammock, Bruce D.. AU - Kltz, Dietmar. PY - 2013/12. Y1 - 2013/12. N2 - This study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na+ and ClOconcentrations were also measured and ...
TY - JOUR. T1 - Molecular cloning of human ornithine aminotransferase mRNA. AU - Inana, G.. AU - Totsuka, S.. AU - Redmond, M.. AU - Dougherty, T.. AU - Nagle, J.. AU - Shiono, T.. AU - Ohura, T.. AU - Kominami, E.. AU - Katunuma, N.. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1986. Y1 - 1986. N2 - The isolation and characterization of a cDNA clone for the mRNA of human ornithine aminotransferase (OATase; ornithine-oxo-acid aminotransferase; L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13), a nonabundant mitochondrial matrix enzyme that is severely deficient in a hereditary chorioretinal degenerative disease (gyrate atrophy), is described. Human liver, retina, and retinoblastoma (Y79) mRNAs were prepared and tested for the OATase mRNA content by in vitro translation, immunoprecipitation, and NaDodSO4/PAGE. The retinoblastoma cells were found to be expressing this enzyme at a relatively high level. The primary translation product of the OATase mRNA is larger ...
Define carbamyl. carbamyl synonyms, carbamyl pronunciation, carbamyl translation, English dictionary definition of carbamyl. n a radical, NH2CO, that is derived from carbamic acid
TY - JOUR. T1 - Phylogenetic Analysis and Protein Modeling of Plasmodium falciparum Aspartate Transcarbamoylase (ATCase). AU - Depamede, Sulaiman. AU - Menz, Ian. PY - 2011. Y1 - 2011. N2 - Unlike most mammalian cells, Plasmodium sp., are unable to utilize preformed pyrimidine bases and nucleosides hence they are reliant solely on de novo pathway. Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) catalyzes the first committed step in de novo pyrimidine biosynthesis pathway, is a potential target for novel anti-parasitic including antimalarial drugs. P. falciparum ATCase has not been studied extensively. To reveal whether it has a regulatory subunit or no and how its evolution, phylogenetic analysis and protein modeling of ATCase P. falciparum were studied. The structural model can be used to identify the possible differences between active sites of mammalian and Plasmodium enzyme. This is important in a relation with antimalarial drug development. Analogous sequences from P. falciparum were ...
TY - JOUR. T1 - Bioanalysis of 6-diazo-5-oxo-l-norleucine in plasma and brain by ultra-performance liquid chromatography mass spectrometry. AU - Alt, Jesse. AU - Potter, Michelle C.. AU - Rojas, Camilo. AU - Slusher, Barbara. PY - 2015/4/1. Y1 - 2015/4/1. N2 - Glutamine is an abundant amino acid that plays pivotal roles in cell growth, cell metabolism, and neurotransmission. Dysregulation of glutamine-using pathways has been associated with pathological conditions such as cancer and neurodegenerative diseases. 6-Diazo-5-oxo-l-norleucine (DON) is a reactive glutamine analog that inhibits enzymes affecting glutamine metabolism such as glutaminase, 2-N-amidotransferase, l-asparaginase, and several enzymes involved in pyrimidine and purine de novo synthesis. As a result, DON is actively used in preclinical models of cancer and neurodegenerative disease. Moreover, there have been several clinical trials using DON to treat a variety of cancers. Considerations of dose and exposure are especially ...
Kidneys produce ammonium to buffer and excrete acids through metabolism of glutamine. Expression of the glutamine transporter Slc38a3 (SNAT3) increases in kidney during metabolic acidosis (MA), suggesting a role during ammoniagenesis. Potassium depletion and high dietary protein intake are known to elevate renal ammonium excretion. In this study, we examined SNAT3, phosphate-dependent glutaminase (PDG), and phosphoenolpyruvate carboxykinase (PEPCK) regulation during a control (0.36%) or low-K(+) (0.02%) diet for 7 or 14 days or a control (20%) or high-protein (50%) diet for 7 days. MA was induced in control and low-K(+) groups by addition of NH(4)Cl. Urinary ammonium excretion increased during MA, after 14-day K(+) restriction alone, and during high protein intake. SNAT3, PDG, and PEPCK mRNA abundance were elevated during MA and after 14-day K(+) restriction but not during high protein intake. SNAT3 protein abundance was enhanced during MA (both control and low K(+)), after 14-day low-K(+) ...
Propionic acidemia is caused by deficiency of propionyl CoA carboxylase that impairs the supply of succinyl CoA to the citric acid (Krebs) cycle. The Krebs cycle is responsible for obtaining energy from food in the form of ATP. ATP is essential for muscle contraction and correct functioning of all organs including the hearth, the kidney, and the pancreas.. Patients with propionic acidemia develop hyperammonemia at birth that recurs during episodes of metabolic decompensation. We found that plasma levels of the amino acids glutamine/glutamate are reduced in patients with propionic acidemia and decrease, rather than increase (like in urea cycle defects or other types of hyperammonemia) with hyperammonemia. Since alpha-ketoglutarate is the main source of endogenous glutamate/glutamine synthesis, our hypothesis is that chronic hyperammonemia and progressive dysfunction of multiple organs in patients with propionic acidemia is due to a functional insufficiency of the citric acid (Krebs) cycle with ...
Using a highly efficient AAV delivery platform together with potent and specific guide RNAs for CRISPR-Cas9, we and others have demonstrated efficient in vivo genome editing in mouse models (25). Following cleavage by endonuclease, HDR is generally a less efficient pathway compared to NHEJ, which creates gene-disabling indels. AAV vector has exhibited advantages as an efficient vehicle to deliver donor DNA both in vitro and in vivo. We previously demonstrated successful correction of a G-to-A mutation in 10% of OTC alleles in the liver of newborn OTC spfash mice by a CRISPR-Cas9-mediated HDR approach (25). However, this approach cannot benefit all OTC-deficient patients because disease-causing mutations and large deletions are found scattered at approximately 320 different positions throughout the OTC gene (27). The HDR-mediated gene-targeting approach described in the current study could be broadly applied to all patients carrying mutations in the same causal gene, similar to gene replacement ...
Chrysomya Robineau-Desvoidy (Diptera: Calliphoridae) is a genus of blowfly commonly observed in tropical and subtropical countries of the Old World. Species in this genus are vectors of bacteria, protozoans and helminths, cause myiasis, are predators of other carrion insects, and are important forensic indicators. Hypotheses concerning the evolution of sex determination, larval anatomy and genome size in Chrysomya have been difficult to evaluate because a robust phylogeny of the genus was lacking. Similarly, the monophyly of subgenera was uncertain. The phylogeny of Chrysomya spp. was reconstructed based on 2386 bp of combined mitochondrial cytochrome oxidase subunit I (COI) and nuclear carbamoylphosphate synthetase (CPS) genes. Maximum parsimony (MP), maximum likelihood (ML) and Bayesian analysis (BA) differed only slightly in the resulting tree topology. Chrysomya was monophyletic. Monogenic reproduction is almost certainly derived rather than, as has been suggested, primitive within the ...
Objective: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated.. Methods and results: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4). Transgenic expression of green fluorescent protein emerged upon hepatocyte differentiation when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase gene but was constitutive from the ubiquitin gene promoter. Human AT-MSCs were transplanted into livers of ...
In the linear pathway (Figure 1A), GLU is converted to acetylglutamate (Ac-GLU) by N-acetylglutamate synthase (NAGS, encoded by argA) which is inhibited by ARG through negative feedback regulation [36],[39]. Sequential catalytic reactions catalyzed by the next three enzymes, N-acetylglutamate kinase (NAGK, encoded by argB), N-acetylglutamate semialdehyde dehydrogenase (encoded by argC) and N-acetylornithine transaminase (encoded by argD), which are common in the three pathways (Figure 1), yield N-acetylornithine (Ac-ORN) [34]. The next step, which distinguishes the linear pathway from the other two pathways, is deacetylation of Ac-ORN by AOase to yield ORN [40],[41]. The next and final steps are carried out by ornithine carbamoyltransferase (OTC or OTCase, encoded by argF), argininosuccinate synthase (encoded by argG) and argininosuccinate lyase (encoded by argH), which finally yield ARG [35]. This pathway has been found in a few species such as Myxococcus xanthus [41] and E. coli [36].. In many ...
1E19: The 1.5-A Resolution Crystal Structure of the Carbamate Kinase-Like Carbamoyl Phosphate Synthetase from the Hyperthermophilic Archaeon Pyrococcus Furiosus, Bound to Adp, Confirms that This Thermoestable Enzyme is a Carbamate Kinase, and Provides Insights Into Substrate Binding and Stability in Carbamate Kinases
TY - JOUR. T1 - Crystal structure of human ornithine decarboxylase at 2.1 Å resolution. T2 - Structural insights to antizyme binding. AU - Almrud, Jeffrey J.. AU - Oliveira, Marcos A.. AU - Kern, Andrew D.. AU - Grishin, Nick V.. AU - Phillips, Margaret A.. AU - Hackert, Marvin L.. PY - 2000/1/7. Y1 - 2000/1/7. N2 - The polyamines spermidine and spermine are ubiquitous and required for cell growth and differentiation in eukaryotes. Ornithine decarboxylase (ODC, EC 4.1.1.17) performs the first step in polyamine biosynthesis, the decarboxylation of omithine to putrescine. Elevated polyamine levels can lead to down-regulation of ODC activity by enhancing the translation of antizyme mRNA, resulting in subsequent binding of antizyme to ODC monomers which targets ODC for proteolysis by the 26S proteasome. The crystal structure of ornithine decarboxylase from human liver has been determined to 2.1 Å resolution by molecular replacement using truncated mouse ODC (Δ425-461) as the search model and ...
Some insects only have one annual crack at the whip. Emerging from a state of suspended animation during winter - known as diapause - many insects have a single season to successfully complete development and reproduce. And when your life-cycle is tightly synchronised with other seasonal events, such as fruit production, accurate timing is essential. Yet little was known about how pupae reactivate development when they terminate diapause ready for a new season.. According to Gregory Ragland from the University of Florida, USA, larvae of the apple maggot fly (Rhagoletis pomonella) are a major apple pest in the US. However, R. pomonella larvae infested indigenous hawthorn fruits - which fruit later than apples - long before settlers brought apples to North America, so the flies that switched host had to evolve rapidly to adjust when they emerge from diapause to catch early fruiting apples. Knowing that R. pomonella is studied by scientists intrigued by rapid species evolution, Ragland, Jeffery ...
Orotic Acid and/or Orotidine may be elevated secondary to hyperammonemia. Increased excretion of Orotic Acid is seen in Ornithine Transcarbamylase (OTC) Deficiency as well as Hereditary Orotic Aciduria ...
Ornithine carbamoyltransferase (OTC) catalyzes the reversible transfer of the carbamoyl group from carbamoyl phosphate (CP) to the Nε atom of L-ornithine (ORN) to produce L-citrulline. There are two types of the enzyme - anabolic (aOTC) and catabolic (cOTC). Anabolic OTCs participate in the urea cycle and L-arginine biosynthesis. Catabolic OTCs are part of the catabolic arginine deiminase pathway found in a number of microorganisms. The reported structure is for the anabolic enzyme from pathogen Vibrio vulnificus. The structure has three monomers in the asymmetric unit which form the physiologically active trimer. One of the three enzyme subunits is entrapped in a complex with its first substrate carbamoyl phosphate and its inhibitor arginine. That complex provides additional structural insights into mechanism of inhibition by arginine. It shows that binding of CP together with arginine causes closure of interdomain cleft and brings catalytic loops K*STRTR, B2-H3 and SMG into the catalytic site ...
Phosphoinositide signalling regulates a series of important neuronal processes that are thought to be altered in mood disorders. Furthermore, mood-stabilizing drugs inhibit key enzymes that regulate phosphoinositide production and alter neuronal growth cone morphology in an inositol-reversible manner. Inositol is taken up by neurons from the extracellular fluid, presumably via membrane transporters; it can also be synthesized by the enzyme MIP-synthase (myo-inositol-1-phosphate synthase) and, in addition, it is generated by inositol phospholipid hydrolysis. The neuronal-specific HMIT (H+-myo-inositol transporter) represents a potential regulator of inositol signalling in neurons that warrants further investigation.. ...
Inositol levels, maintained by the biosynthetic enzyme inositol-3-phosphate synthase (Ino1), are altered in a range of disorders, including bipolar disorder and Alzheimer's disease. To date, most inositol studies have focused on the molecular and cellular effects of inositol depletion without considering Ino1 levels. Here we employ a simple eukaryote, Dictyostelium discoideum, to demonstrate distinct effects of loss of Ino1 and inositol depletion. We show that loss of Ino1 results in an inositol auxotrophy that can be rescued only partially by exogenous inositol. Removal of inositol supplementation from the ino1(-) mutant resulted in a rapid 56% reduction in inositol levels, triggering the induction of autophagy, reduced cytokinesis, and substrate adhesion. Inositol depletion also caused a dramatic generalized decrease in phosphoinositide levels that was rescued by inositol supplementation. However, loss of Ino1 triggered broad metabolic changes consistent with the induction of a catabolic state that
The unikonts have a triple-gene fusion that is lacking in the bikonts. The three genes that are fused together in the unikonts, but not bacteria or bikonts, encode enzymes for synthesis of the pyrimidine nucleotides: carbamoyl phosphate synthase, dihydroorotase, aspartate carbamoyltransferase. This must have involved a double fusion, a rare pair of events, supporting the shared ancestry of Opisthokonta and Amoebozoa.. Cavalier-Smith[1] originally proposed that unikonts ancestrally had a single flagellum and single basal body. This is unlikely, however, as flagellated opisthokonts, as well as some flagellated Amoebozoa, including Breviata, actually have two basal bodies, as in typical 'bikonts' (even though only one is flagellated in most unikonts). This paired arrangement can also be seen in the organization of centrioles in typical animal cells. In spite of the name of the group, the common ancestor of all 'unikonts' was probably a cell with two basal bodies.. ...
Astrocytes are the site of early dysfunction and damage in Mn neurotoxicity. Astrocytes are the most abundant CNS cells (~50% by volume), and they perform numerous essential functions for normal neuronal activity, such as glutamate uptake, glutamine release, K+ and H+ buffering and volume regulation [36, 75, 76]. Astrocytes accumulate up to 50-fold higher Mn concentrations compared to neurons, thus serving as the main homeostatic and storage site for this metal [75, 77]. The intracellular concentration of Mn in astrocytes is ~50-75 μM where it is an essential cofactor for the astrocyte-specific enzyme glutamine synthetase, which catalyzes the conversion of glutamate to glutamine [78, 79]. The excessive accumulation of Mn in astrocytes mediates neurotoxicity primarily by oxidative stress and impairment of glutamate transporters [80, 81]. Mn toxicity has been shown to cause astrocytic alterations in primate models, and exposure of pathophysiologically relevant Mn concentrations in astrocytes in ...
Cytochrome bc1 complex is a dimeric multisubunit electron transport protein in the inner-mitochondrial membrane and is a proven drug target in the prevention and treatment of malaria. Cytochrome bc1 complex is essential for Plasmodium falciparum as it maintains a pool of ubiquinone for the enzyme dihydroorotate dehydrogenase, which catalyzes the ubiquinone-mediated oxidation of dihydroorotate to orotate, in the pyrimidine biosynthesis pathway. The pyrimidine biosynthesis pathway is critical for the survival of P. falciparumbecause it cannot salvage pyrimidines and therefore is completely dependent on de novo pyrimidine synthesis. Inhibition of either cytochrome bc1 complex or dihydroorotate dehydrogenase has been shown to result in death of the parasite. We are currently focusing on the development of atovaquone-based and quinolone-based inhibitors of cytochrome bc1 complex. Publications:. 15) Hossain, M. I.; Thomas, A. G.; Mahdi, F.; Adam, A. T.; Woodard, M. M.; Paris, J. J.; Slusher, B. S.; ...
Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8+ T cell responses and ameliorated liver ...
Mechanism of Action. Leflunomide is an immunomodulatory drug inhibiting mitochondrial enzyme dihydroorotate dehydrogenase (an enzyme involved in de novo pyrimidine synthesis) (abbreviation DHODH), which plays a key role in the de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP). The inhibition of human DHODH by A77 1726, the active metabolite of leflunomide, occurs at levels (approximately 600 nM) that are achieved during treatment of rheumatoid arthritis (RA). Leflunomide prevents the expansion of activated and autoimmune lymphocytes by interfering with their cell cycle progression while nonlymphoid cells are able to use another pathway to make their ribonucleotides by use of salvage pyrimidine pathway, which makes them less dependent on de novo synthesis. Genuine antiproliferative activity has been proven. In addition, several experimental models (both in vivo and in vitro) have demonstrated an anti-inflammatory effect. This double action is supposed to slow ...
Acute myeloid leukemia (AML) is a devastating disease, with the majority of patients dying within a year of diagnosis. For patients with relapsed/refractory AML, the prognosis is particularly poor with currently available treatments. Although genetically heterogeneous, AML subtypes share a common differentiation arrest at hematopoietic progenitor stages. Overcoming this differentiation arrest has the potential to improve the long-term survival of patients, as is the case in acute promyelocytic leukemia (APL), which is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. Treatment of APL with all-trans retinoic acid (ATRA) induces terminal differentiation and apoptosis of leukemic promyelocytes, resulting in cure rates of over 80%. Unfortunately, similarly efficacious differentiation therapies have, to date, been lacking outside of APL. Inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine synthesis pathway, was ...
Order Recombinant Yersinia pestis bv Antiqua Ornithine carbamoyltransferase argI 01015969174 at Gentaur Yersinia pestis bv. Antiqua Ornithine carbamoyltransferase (argI)
Kit Component:- KN308465G1, Isyna1 gRNA vector 1 in pCas-Guide vector- KN308465G2, Isyna1 gRNA vector 2 in pCas-Guide vector- KN308465D, donor vector…
Herein, we describe a case of a now 28-month-old boy who presented at the age of 17 months with four episodes of recurrent vomiting and somnolence during a period of four months with increasing severity. A comprehensive clinical and metabolic evaluation revealed normal blood pH and blood glucose, normal cerebral computed tomography and electroencephalogram but an elevated plasma ammonia concentration, which raised the suspicion of a urea cycle disorder. The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline suggested the diagnosis of ornithine transcarbamylase (OTC) deficiency, which was confirmed by molecular genetic testing revealing the novel hemizygous mutation c.535C , T (p.Leu179Phe) of the OTC gene. After restitution of anabolism by administration of parenteral glucose, substitution of citrulline and detoxification of ammonia with sodium benzoate, the patient recovered rapidly and is in a stable metabolic and neurological state since then. This case ...
Order Recombinant Prochlorococcus marinus subsp pastoris Indole-3-glycerol phosphate synthase trpC 01015965649 at Gentaur Prochlorococcus marinus subsp. pastoris Indole-3-glycerol phosphate synthase (trpC)
DESIGN: Pilot, Phase II, double-blind, placebo-controlled study. JUSTIFICATION: In the literature one does not find a pharmacological treatment that changes the natural history of Spinocerebellar ataxtia type 3 (SCA3). Patients with this disease invariably become dependent.. OBJECTIVES I. To determine safety and tolerability of phenylbutyrate in patients with SCA3.. II. To provide early subsidies on the efficacy of phenylbutyrate in SCA3.. DURATION: 12 months of a double-blind study.. PLACE OF REALIZATION: Hospital de Clínicas de Porto Alegre, Brazil.. NUMBER OF PATIENTS: 20 patients.. CONCOMITANT MEDICATIONS: There are no concomitant medications that are prohibited unless they affect safety parameters of this study (hemogram and platelets; fasting serum glucose, AST, ALT, Gamma-GT, Bilirubins, Prothrombin time, Creatinine, Urea, Na, K, chlorides and arterial gasometry; electrocardiogram and echocardiogram).. MEDICATIONS UNDER INVESTIGATION: Powdered sodium phenylbutyrate in sachets containing ...
Heat shock proteins (HSPs) are highly conserved and present in organisms under normal physiological conditions and function in protein folding, degradation and localization. HSPs are also synthesized in response to environmental stressors such as heat, anoxia, desiccation and cold. These molecular chaperones protect other proteins from irreversible denaturation during stress, thereby maintaining proteostasis and allowing cells to survive unfavorable conditions. Artemia franciscana, commonly known as brine shrimp, are micro-crustaceans that live in harsh aquatic environments and experience high salinity, extreme temperatures, variable water levels, and hypoxia. In anticipation of stressful conditions, A. franciscana alter their life cycle by releasing cysts that enter diapause. Nauplii (larvae) emerge after diapause termination or when favorable conditions return. The effect of cold shock on three HSPs, HSP90, HSP70 and HSP40 was studied in the nauplii of A. franciscana during 6 h of cold-shock ...
Autor: Molla-Morales, A. et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2011; Keywords: mesophyll growth|br/|carbamoyl phosphate synthetase|br/|reticulate leaves|br/|amino acid biosynthesis|br/|carbamoyl-phosphate synthetase|br/|phosphoenolpyruvate/phosphate-translocator|br/|chloroplast biogenesis|br/|mutational analysis|br/|shikimate pathway|br/|gene-expression|br/|bundle-sheath|br/|nitric-oxide|br/|thaliana|br/|leaves; Titel: Analysis of ven3 and ven6 reticulate mutants reveals the importance of arginine biosynthesis in Arabidopsis leaf development
TY - JOUR. T1 - Behavioural response of wheat bulb fly (Delia coarctata, Diptera: Anthomyiidae) larvae to the primary plant metabolite carbon dioxide. AU - Rogers, Craig D. AU - Evans, KA. AU - Parker, JP. AU - Pappa, V. PY - 2013/12. Y1 - 2013/12. N2 - Wheat bulb fly (WBF) larvae use chemotaxis to orientate towards host-plant rootexudates. This study aimed to investigate the role of the primary plant metabolite carbon dioxide (CO2) in host-plant location by WBF. Arena based behavioural experiments were used to identify whether CO2 induced chemotaxis (directional movement in response to a chemical stimulus) or kinesis (non-directional movement in response to a stimulus) from WBF larvae. No chemotactic response was observed when larvae were presented to a point source of CO2. However, elevated levels of CO2 induced kinesis, with both track length and tortuosity (number of twists and turns in the movement path) increasing at elevated CO2 levels of 1000-2000ppm, demonstrating increased searching ...
Mechanisms to facilitate the distribution and cellular uptake of copious amounts of urea synthesized during winter acclimatization could potentially include increased expression of urea transporters in the liver and other organs. Whether this occurs is an open question, although, in R. sylvatica, elevated urea in the absence of tissue dehydration reduces the abundance of these proteins in the kidney and urinary bladder (Rosendale et al., 2012). Urea permeability could be enhanced through other mechanisms. For example, expression of the gene for HC-3, one of several amphibian orthologs of the mammalian aquaporin, AQP3, which transports glycerol and urea in addition to water, increases during cold acclimation in various tissues of a freeze-tolerant tree frog (Zimmerman et al., 2007).. Urea accrual in Alaskan frogs likely stemmed from cold-induced oliguria and high activity of the regulatory enzyme carbamoyl phosphate synthetase I (Schiller et al., 2008), as well as a targeted reorganization of ...
In toxicological research, immortalized human hepatocytes provide a useful alternative to primary hepatocytes because interindividual variability in the expression of drug-metabolizing enzymes and drug transporters can largely be eliminated. However, it is essential that the cell line retain the original phenotype. The purpose of this study was to characterize a novel spontaneously immortalized human hepatocyte cell line, HC-04, with respect to the transcript and functional protein expression profile for the major drug-metabolizing enzymes and transmembrane transporters. HC-04 cells retained hepatocyte-specific function including albumin production and ornithine transcarbamoylase and glucose-6-phosphatase activity. Most of the major CYP forms were expressed at basal levels and responsive to inducing agents. In particular, CYP3A4 was expressed abundantly, and HC-04 cells were able to metabolize the CYP3A4 probe, midazolam, at a rate similar to primary human hepatocytes. Furthermore, the major ...
The metabolism of the glycation product fructose-ϵ-lysine in Escherichia coli involves its ATP-dependent phosphorylation by a specific kinase (FrlD), followed by the conversion of fructoselysine 6-phosphate into glucose 6-phosphate and lysine by fructoselysine-6-phosphate deglycase (FrlB), which is distantly related to the isomerase domain of glucosamine-6-phosphate synthase. As shown in the present work, several bacterial operons comprise: (1) a homologue of fructoselysine-6-phosphate deglycase; (2) a second homologue of the isomerase domain of glucosamine-6-phosphate synthase, more closely related to it; and (3) components of a novel phosphotransferase system, but no FrlD homologue. The FrlB homologue (GfrF) and the closer glucosamine-6-phosphate synthase homologue (GfrE) encoded by an Enterococcus faecium operon were expressed in E. coli and purified. Similar to FrlB, GfrF catalysed the reversible conversion of fructoselysine 6-phosphate into glucose 6-phosphate and lysine. When incubated ...
(4-(Benzyl(methyl)carbamoyl)phenyl)boronic acid 874219-49-5 NMR spectrum, (4-(Benzyl(methyl)carbamoyl)phenyl)boronic acid H-NMR spectral analysis, (4-(Benzyl(methyl)carbamoyl)phenyl)boronic acid C-NMR spectral analysis ect.
1GR0: Crystal Structure of Inositol 1-Phosphate Synthase from Mycobacterium Tuberculosis, a Key Enzyme in Phosphatidylinositol Synthesis