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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of insulin and the insulin mimetic agent "vanadate" were studied on the activities of alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and arginase in the cytosolic and the mitochondrial fractions of the kidney in control and alloxan induced diabetic rats. An enhancement in the activities of these enzymes were noted in both the fractions of diabetic kidney. Vanadate treatment (0.6 mg/ml in drinking water) of alloxan induced diabetic rats restored the activities of these enzymes almost completely in the cytosolic and partially in the mitochondrial fractions. Vanadate treatment also normalized hyperglycaemia without altering the depressed levels of insulin secretion in diabetic rats. The effect of insulin treatment was found to be the same as that of vanadate in diabetic rats.
Biochem Mol Biol Int 1996 Nov
PMID:Effects of vanadate and insulin on the activities of selected enzymes of amino acid metabolism in alloxan diabetic rat kidney. 895 44

Expression of the catabolic gene encoding arginase in Saccharomyces cerevisiae, CAR1, is controlled by multiple nitrogen signals, such as the presence of the inducer, arginine, and the nature and amount of the nitrogen source. The present study has determined or confirmed the identity of the proteins involved in these different controls, as well as their targets in the CAR1 promoter. We show that Gln3p activates CAR1 expression through the GATAA sequences in the absence of an optimal nitrogen source, such as ammonia, glutamine or asparagine. Ume6p, which also controls the expression of early meiotic genes, represses CAR1 expression through a sequence called URS, as a function of nitrogen availability. Thus, the responses to the quality of the nitrogen source and to nitrogen starvation are achieved through different cis- and trans-regulatory elements. At least one of the multiple Rap1p and Abf1p binding sites is required for the basal transcription of the gene. The UAS(arg), containing the previously defined "arginine boxes" is the region that responds to the inducer through the action of the ArgRp-Mcm1p proteins, and its deletion alone significantly affects growth on arginine as sole nitrogen source. The functional UAS(arg) is about 60 nucleotides long, and contains two sequences homologous to the binding site for MADS-box proteins, to which ArgRIp and Mcm1p belong. No obvious palindromic sequence similar to the binding site of Gal4p, Ppr1p or Put3p is present in the UAS(arg), although ArgRIIp contains a Zn(II)2Cys6 motif. Interestingly, we have found that induction of CAR1 expression by arginine in the presence of an optimal nitrogen source is counteracted by Gln3p, independently of its action at the GATAA sequences.
Mol Gen Genet 1997 Feb 20
PMID:Integration of the multiple controls regulating the expression of the arginase gene CAR1 of Saccharomyces cerevisiae in response to differentnitrogen signals: role of Gln3p, ArgRp-Mcm1p, and Ume6p. 906 90

As a toxic metabolic byproduct in mammals, excess ammonia is converted into urea by a series of five enzymatic reactions in the liver that constitute the urea cycle. A portion of this cycle takes place in the mitochondria, while the remainder is cytosolic. Liver arginase (L-arginine ureahydrolase, A1) is the fifth enzyme of the cycle, catalyzing the hydrolysis of arginine to ornithine and urea within the cytosol. Patients deficient in this enzyme exhibit hyperargininemia with episodic hyperammonemia and long-term effects of mental retardation and spasticity. However, the hyperammonemic effects are not so catastrophic in arginase deficiency as compared to other urea cycle defects. Earlier studies have suggested that this is due to the mitigating effect of a second isozyme of arginase (AII) expressed predominantly in the kidney and localized within the mitochondria. In order to explore the curious dual evolution of these two isozymes, and the ways in which the intriguing, aspects of AII physiology might be exploited for gene replacement therapy of AI deficiency, the cloned cDNA for human AI was inserted into an expression vector downstream from the mitochondrial targeting leader sequence for the mitochondrial enzyme ornithine transcarbamylase and transfected into a variety of recipient cell types. AI expression in the target cells was confirmed by northern blot analysis, and competition and immunoprecipitation studies showed successful translocation of the exogenous AI enzyme into the transfected cell mitochondria. Stability studies demonstrated that the translocated enzyme had a longer half-life than either native cytosolic AI or mitochondrial AII. Incubation of the transfected cells with increasing amounts of arginine produced enhanced levels of mitochondrial AI activity, a substrate-induced effect that we have previously seen with native AII but never AI. Along with exploring the basic biological questions of regulation and subcellular localization in this unique dual-enzyme system, these results suggest that the mitochondrial matrix space may be a preferred site for delivery of enzymes in gene replacement therapy.
Somat Cell Mol Genet 1996 Nov
PMID:Delivery of cytosolic liver arginase into the mitochondrial matrix space: a possible novel site for gene replacement therapy. 913 Oct 18

The antiaggregating effect of L-arginine and polyamines (putrescine, spermidine and spermine) was studied in platelets of normal and diabetic rats (120 mg/Kg alloxan, i.p.). This effect was compared with insulin. The assays of platelet aggregation were carried out using platelet-rich plasma (PRP) obtained from both groups of animals. The platelet aggregation test were first standardized by using PRP obtained from human health donors. 2.5 mumoles/ml ADP, 250 mumoles/ml epinephrine and 0.4 U/ml of thrombin were used as inductors of platelet aggregation. 60% of inhibition was observed with 10 microM of L-arginine or polyamines in PRP of normal rats, and 50% with PRP of diabetic rats when thrombin was used as an agonist. These results show that L-arginine and the polyamines putrescine, spermidine and spermine have an antagonist action in platelet aggregation. In addition, we demonstrated the platelet arginase activity not only in rat platelets but also in human, was less under hyperglycaemia. The activity of this enzyme has been associated with polyamine synthesis, required to regulate platelet function.
Biochem Mol Biol Int 1997 Oct
PMID:Inhibition of platelet aggregation by L-arginine and polyamines in alloxan treated rats. 935 Mar 38

Two forms of arginase, both catalyzing the hydrolysis of arginine to ornithine and urea, are found in animals ranging from amphibians to mammals. In humans, inherited deficiency of hepatic or type I arginase results in hyperargininemia, a syndrome characterized by periodic episodes of hyperammonemia, spasticity, and neurological deterioration. In these patients, a second extrahepatic or type II arginase activity is significantly increased, an induction that may partially compensate for the lack of AI activity and apparently mitigates some of the clinical effects of the condition. Cloning and characterization of the human AII cDNA was recently accomplished. The cloning, sequencing, and partial characterization of the mouse and rat AII cDNAs are reported herein. The DNA sequences predicted polypeptides of 354 amino acids, including a N-terminal mitochondrial import signal. Sequence homology to the human type II arginase, arginase activity data, and immunoprecipitation with an anti-AII antibody confirm the identity of these cloned genes as rodent extrahepatic type II arginases.
Mol Genet Metab 1998 Mar
PMID:Cloning and characterization of the mouse and rat type II arginase genes. 960 38

Nitric oxide (NO) has been associated with lung inflammation following exposure to silica. L-arginine can be converted to NO and L-citrulline by nitric oxide synthase (NOS), or into urea and L-ornithine by arginase. We tested the hypothesis that after instillation of silica into rat lungs in vivo, lung inflammatory cells increase L-arginine metabolism by both NOS and arginase, which is associated with an increase in L-arginine uptake. We isolated lung inflammatory cells 3 d after silica or saline (control) exposure. The uptake of [3H]L-arginine at 24 h by cells from silica-exposed lungs (73.9 +/- 4.8%) was significantly greater than uptake by control cells (24.7 +/- 2.2%; P < 0.05) and was a saturable process. The greater [3H]L-arginine uptake by cells from silica-exposed lungs was associated with greater NO and urea production than by control cells. The uptake of [3H]L-arginine by cells from control or silica-exposed lungs was blocked in a dose-dependent manner by L-ornithine (an inhibitor of L-arginine transport) and by Nomega-nitro-L-arginine methyl ester (L-NAME) (an NOS inhibitor), but not by L-valine (an arginase inhibitor). The production of NO by cells from silica-exposed lungs was completely blocked by L-NAME. The addition of L-arginine to media resulted in dose-dependent production of NO and urea. The results show that lung inflammatory cells increase L-arginine uptake and metabolism by both NOS and arginase following in vivo silica exposure. The increase in L-arginine uptake may represent a mechanism to maintain an intracellular supply of this amino acid. NO can react to generate peroxynitrite, a potential mediator of lung injury following silica exposure.
Am J Respir Cell Mol Biol 1998 Aug
PMID:L-arginine uptake and metabolism by lung macrophages and neutrophils following intratracheal instillation of silica in vivo. 969 4

We have recently reported the synthesis of urea from ammonia, glutamine and arginine in enterocytes of postweaning pigs. The present study was conducted to determine the compartmentation and kinetics of urea cycle enzymes in these cells. Carbamoyl phosphate synthase I (CPS I) and ornithine carbamoyltransferase (OCT) were located exclusively in mitochondria, whereas argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were found in the cytosol. Arginase isozymes were present in both the cytosol and mitochondria of enterocytes, and differed in their sensitivity to heat inactivation. Except for OCT, Vmax values of urea cycle enzymes were much lower in enterocytes than in the liver of pigs, and vice versa for their Km values. Because of a low rate of ureagenesis in enterocytes compared with the liver, intestinal urea cycle enzymes may function primarily to synthesize citrulline. The co-localization of CPS I and OCT and a high activity of OCT in enterocyte mitochondria favors the intestinal synthesis of citrulline from ammonia, HCO3- and ornithine. Low activities of cytosolic ASS and ASL minimize the conversion of citrulline into arginine and therefore, the recycling of citrulline into ornithine via arginase in postweaning-pig enterocytes. These kinetic properties of intestinal urea cycle enzymes maximize the net synthesis of citrulline from glutamine and explain the release of large amounts of citrulline by the pig small intestine. The two compartmentally separated arginase isozymes in enterocytes may play an important role in regulating the intestinal metabolism of proline, nitric oxide and polyamines.
Comp Biochem Physiol B Biochem Mol Biol 1998 Mar
PMID:Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes. 973 36

Hyperargininemia is a rare autosomal recessive disorder that results from a deficiency of hepatic type I arginase. At the genetic level, this deficiency in arginase activity is a consequence of random point mutations throughout the gene that lead to premature termination of the protein or to substitution mutations. Given the high degree of sequence homology between human liver and rat liver enzymes, we have mapped both patient and nonpatient mutations of the human enzyme onto the structure of the rat liver enzyme to rationalize the molecular basis for the low activities of these mutant arginases. Mutations identified in hyperargininemia patients affect the structure and function of the enzyme by compromising active-site residues, packing interactions in the protein scaffolding, and/or quaternary structure by destabilizing the assembly of the arginase trimer.
Mol Genet Metab 1998 Aug
PMID:Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. 975 14

Nitric oxide and species derived from it have a wide range of biological functions. Some applications of electron paramagnetic resonance (EPR) spectroscopy are reviewed, for observing nitrosyl species in biological systems. Nitrite has long been used as a food preservative owing to its bacteriostatic effect on spoilage bacteria. Nitrosyl complexes such as sodium nitroprusside, which are added experimentally as NO-generators, themselves produce paramagnetic nitrosyl species, which may be seen by EPR. We have used this to observe the effects of nitroprusside on clostridial cells. After growth in the presence of sublethal concentrations of nitroprusside, the cells show they have been converted into other, presumably less toxic, nitrosyl complexes such as (RS)2Fe(NO)2. Nitric oxide is cytotoxic, partly due to its effects on mitochondria. This is exploited in the destruction of cancer cells by the immune system. The targets include iron-sulfur proteins. It appears that species derived from nitric oxide such as peroxynitrite may be responsible. Addition of peroxynitrite to mitochondria led to depletion of the EPR-detectable iron-sulfur clusters. Paramagnetic complexes are formed in vivo from hemoglobin, in conditions such as experimental endotoxic shock. This has been used to follow the course of production of NO by macrophages. We have examined the effects of suppression of NO synthase using biopterin antagonists. Another method is to use an injected NO-trapping agent, Fe-diethyldithiocarbamate (Fe-DETC) to detect accumulated NO by EPR. In this way we have observed the effects of depletion of serum arginine by arginase. In brains from victims of Parkinson's disease, a nitrosyl species, identified as nitrosyl hemoglobin, has been observed in substantia nigra. This is an indication for the involvement of nitric oxide or a derived species in the damage to this organ.
Spectrochim Acta A Mol Biomol Spectrosc 1998 Dec
PMID:Applications of electron paramagnetic resonance spectroscopy to study interactions of iron proteins in cells with nitric oxide. 997 26

Nitric oxide (NO) is synthesized from a unique precursor, arginine, by nitric oxide synthase (NOS). In brain cells, arginine is supplied by protein breakdown or extracted from the blood through cationic amino acid transporters (CATs). Arginine can also be recycled from the citrulline produced by NOS activity, through argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) activities, and metabolized by arginase. NOS, AS and AL constitute the so-called citrulline-NO cycle. In order to better understand arginine transport, recycling and degradation, we studied the regional distribution of cells expressing CAT1, CAT3, AS, AL, neuronal NOS (nNOS) and arginase II (AII) in the adult rat brain by non-radioisotopic in situ hybridization (ISH). CAT1, AL and AII presented an ubiquitous neuronal and glial expression, whereas CAT3 and AS were confined to neurons. nNOS was restricted to scattered neurons and a few brain nuclei and layers. We demonstrate by this study that cells expressing nNOS all appear to express the entire citrulline-NO cycle, whereas numerous cells expressing AL do not express AS. The differential expression of these genes within the same anatomical structure could indicate that intercellular exchanges of citrulline-NO cycle metabolites are relevant. Thus vicinal interactions should be taken into account to study their regulatory mechanisms.
Brain Res Mol Brain Res 1999 Jul 05
PMID:L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study. 1040 71


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