Arginase
Hyperargininemia
Aminocaproates
Nitric Oxide
Nitric Oxide Synthase Type II
Ornithine Carbamoyltransferase
Nitric Oxide Synthase
Urea
Cationic Amino Acid Transporter 2
Expression of arginase II and related enzymes in the rat small intestine and kidney. (1/943)
Arginase, which catalyzes the conversion of arginine to urea and ornithine, and consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Arginine is also used for the synthesis of nitric oxide and creatine phosphate, while ornithine is used for the synthesis of polyamines and proline, and thus collagen. Arginase II mRNA and protein are abundant in the intestine (most abundant in the jejunum and less abundant in the ileum, duodenum, and colon) and kidney of the rat. In the kidney, the levels of arginase II mRNA do not change appreciably from 0 to 8 weeks of age. In contrast, arginase II mRNA and protein in the small intestine are not detectable at birth, appear at 3 weeks of age, the weaning period, and their levels increase up to 8 weeks. On the other hand, mRNAs for ornithine aminotransferase (OAT), ornithine decarboxylase, and ornithine carbamoyltransferase (OCT) are present at birth and their levels do not change much during development. Arginase II is elevated in response to a combination of bacterial lipopolysaccharide, dibutyryl cAMP, and dexamethasone in the kidney, but is not affected by these treatments in the small intestine. Immunohistochemical analysis of arginase II, OAT, and OCT in the jejunum revealed their co-localization in absorptive epithelial cells. These results show that the arginase II gene is regulated differentially in the small intestine and kidney, and suggest different roles of the enzyme in these two tissues. The co-localization of arginase II and the three ornithine-utilizing enzymes in the small intestine suggests that the enzyme is involved in the synthesis of proline, polyamines, and/or citrulline in this tissue. (+info)Arginase from human full-term placenta. (2/943)
Arginase was purified about 1800-fold from extracts of human full-term placenta; the enzyme appeared to be homogenous by disc electrophoresis and molecular-sieve chromatography. The mol. wt. determination by gel filtration and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis yielded a value of 70000 for the most pure and the partially purified enzyme. The human placenta arginase is a metalloenzyme with an optimum pH of 9.1. The Km for L-arginine is 27 mM. L-Ornithine and L-lysine show competitive inhibition with Ki values of 6.3 and 14 mM respectively. (+info)Glucocorticoids mediate the enhanced expression of intestinal type II arginase and argininosuccinate lyase in postweaning pigs. (3/943)
Arginine metabolism is enhanced in the small intestine of weanling pigs, but the molecular mechanism(s) involved is not known. The objectives of this study were to determine the following: 1) whether glucocorticoids play a role in induction of intestinal arginine metabolic enzymes during weaning; 2) whether the induction of enzyme activities was due to increases in corresponding mRNA levels; and 3) the identity of the arginase isoform(s) expressed in the small intestine. Jejunum was obtained from 29-d-old weaned pigs that were or were not treated with 17-beta-hydroxy-11beta-(4-dimethylaminophenyl)17alpha-(prop- 1-ynyl)es tra-4,9-dien-3-one (RU486, an antagonist of glucocorticoid receptors), or from age-matched suckling pigs. Activities and mRNA levels for type I and type II arginases, argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were determined. Activities of arginase, ASL and ASS increased by 635, 56 and 106%, respectively, in weanling pigs, compared with suckling pigs. RU486 treatment attenuated the increase in arginase activity by 74% and completely prevented the ASL induction in weanling pigs, but had no effect on ASS activity. Pig intestine expresses both type I and type II arginases. On the basis of immunoblot analyses, there was no significant difference in levels of intestinal type I arginase among these three groups of pigs, indicating that changes in arginase activity were due only to type II arginase. The mRNA levels for type II arginase and ASL increased by 135 and 198%, respectively, in weanling pigs compared with suckling pigs, and this induction was completely prevented by RU486. In contrast, ASS mRNA levels did not differ between suckling and weanling pigs. These results suggest that intestinal type II arginase, ASS and ASL are regulated differentially at transcriptional and post-translational levels and that glucocorticoids play a major role in the induction of type II arginase and ASL mRNAs in the small intestine of weanling pigs. (+info)Metabolic capacity for L-citrulline synthesis from ammonia in rat isolated colonocytes. (4/943)
Ammonia is present at high concentration in the colon lumen and is considered a colon cancer suspect. Furthermore, ammonia usually eliminated by the liver in the ornithine cycle is considered highly toxic to cerebral function when present in excess in the blood plasma. Therefore, the metabolic pathways involved in ammonia metabolism in colonocytes were studied in the present study. Rat colonocytes were found equipped with low carbamoylphosphate synthase I activity, high ornithine carbamoyltransferase and arginase activities and low argininosuccinate synthase activity. High (10 and 50 mmol/l) NH4Cl concentrations but not low concentrations (1 and 5 mmol/l) were found able to increase respectively 3- and 10-fold the conversion of radioactive L-arginine to L-citrulline. In contrast, very low capacity for L-citrulline conversion to L-arginine is found in colonocytes. It is concluded that an incomplete ornithine cycle is operative in colonocytes which results in ammonia stimulated L-citrulline production. The contribution of this metabolic pathway in relation to ammonia detoxication by colonocytes is discussed. (+info)Regulation of the genes for arginase isoforms and related enzymes in mouse macrophages by lipopolysaccharide. (5/943)
Arginase exists in two isoforms, the hepatic (arginase I) and extrahepatic types (arginase II). Arginase I is markedly induced in rat peritoneal macrophages and rat tissues in vivo by bacterial lipopolysaccharide (LPS). In contrast, both arginase I and arginase II are induced in LPS-activated mouse peritoneal macrophages. In the present study, expression of arginase isoforms and related enzymes was studied in mouse tissues in vivo and in peritoneal macrophages with RNA blot and immunoblot analyses and enzyme assay. When mice were injected intraperitoneally with LPS, inducible nitric oxide synthase (iNOS) and arginase II were induced early in the lung and spleen. mRNAs for argininosuccinate synthase (AS) and ornithine decarboxylase (ODC) were also induced early. In comparison, arginase I was induced later in the lung. Early induction of iNOS, arginase II, AS, ODC, and cationic amino acid transporter 2 and late induction of arginase I were observed in LPS-activated peritoneal macrophages. These results indicate that the genes for the two arginase isoforms are regulated differentially. Possible roles of the arginase isoforms in the regulation of nitric oxide production and in polyamine synthesis are discussed. (+info)Biochemical and functional profile of a newly developed potent and isozyme-selective arginase inhibitor. (6/943)
An increase in arginase activity has been associated with the pathophysiology of a number of conditions, including an impairment in nonadrenergic and noncholinergic (NANC) nerve-mediated relaxation of the gastrointestinal smooth muscle. An arginase inhibitor may rectify this condition. We compared the effects of a newly designed arginase inhibitor, 2(S)-amino-6-boronohexanoic acid (ABH), with the currently available N(omega)-hydroxy-L-arginine (L-HO-Arg), on the NANC nerve-mediated internal anal sphincter (IAS) smooth-muscle relaxation and the arginase activity in the IAS and other tissues. Arginase caused an attenuation of the IAS smooth-muscle relaxations by NANC nerve stimulation that was restored by the arginase inhibitors. L-HO-Arg but not ABH caused dose-dependent and complete reversal of N(omega)-nitro-L-arginine-suppressed IAS relaxation that was similar to that seen with L-arginine. Both ABH and L-HO-Arg caused an augmentation of NANC nerve-mediated relaxation of the IAS. In the IAS, ABH was found to be approximately 250 times more potent than L-HO-Arg in inhibiting the arginase activity. L-HO-Arg was found to be 10 to 18 times more potent in inhibiting the arginase activity in the liver than in nonhepatic tissues. We conclude that arginase plays a significant role in the regulation of nitric oxide synthase-mediated NANC relaxation in the IAS. The advent of new and selective arginase inhibitors may play a significant role in the discrimination of arginase isozymes and have important pathophysiological and therapeutic implications in gastrointestinal motility disorders. (+info)Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. (7/943)
Activated murine macrophages metabolize arginine by two alternative pathways involving the enzymes inducible NO synthase (iNOS) or arginase. The balance between the two enzymes is competitively regulated by Th1 and Th2 T helper cells via their secreted cytokines: Th1 cells induce iNOS, whereas Th2 cells induce arginase. Whereas the role of macrophages expressing iNOS as inflammatory cells is well established, the functional competence of macrophages expressing arginase remains a matter of speculation. Two isoforms of mammalian arginases exist, hepatic arginase I and extrahepatic arginase II. We investigated the regulation of arginase isoforms in murine bone marrow-derived macrophages (BMMPhi) in the context of Th1 and Th2 stimulation. Surprisingly, in the presence of either Th2 cytokines or Th2 cells, we observe a specific induction of the hepatic isoform arginase I in BMMPhi. Induction of arginase I was shown on the mRNA and protein levels and obeyed the recently demonstrated synergism among the Th2 cytokines IL-4 and IL-10. Arginase II was detectable in unstimulated BMMPhi and was not significantly modulated by Th1 or Th2 stimulation. Similar to murine BMMPhi, murine bone marrow-derived dendritic cells, as well as a dendritic cell line, up-regulated arginase I expression and arginase activity upon Th2 stimulation, whereas arginase II was never detected. In addition to revealing the unexpected expression of arginase I in the macrophage/monocyte lineage, these results uncover a further intriguing parallelism between iNOS and arginase: both have a constitutive and an inducible isoform, the latter regulated by the Th1/Th2 balance. (+info)Carbon and nitrogen repression of arginine catabolic enzymes in Bacillus subtilis. (8/943)
Specific activities of arginase and ornithine aminotransferase, inducible enzymes of arginine catabolism in Bacillus subtilis 168, were examined in cells grown with various carbon and nitrogen sources. Levels of these enzymes were similar in arginine-induced cultures whether glucose or citrate was the carbon source (in contrast to histidase), suggesting that carbon source catabolite repression has only limited effect. In media with combinations of nitrogen sources, glutamine strongly repressed induction of these enzymes by proline or arginine. Ammonium, however, only repressed induction by proline and had no effect on induction by arginine. These effects correlate with generation times in media containing these substances as sole nitrogen sources: growth rates decreased in the order glutamine-arginine-ammonium-proline. Similar phenomena were observed when glutamine or ammonium were added to arginine- or proline-grown cultures, or when arginine or proline were added to glutamine- or ammonium-grown cultures. In the latter cases, an additional feature was apparent, namely a surprisingly long transition between steady-state enzyme levels. The results are compared with those for other bacteria and for eucaryotic microorganisms. (+info)The symptoms of hyperargininemia typically become apparent within the first few months of life and may include:
1. Developmental delays
2. Seizures
3. Hypotonia (low muscle tone)
4. Cognitive impairment
5. Vision loss or blindness
6. Hearing loss
7. Kidney damage or failure
8. Increased risk of infections
Hyperargininemia is usually diagnosed through a combination of clinical evaluation, laboratory testing, and genetic analysis. Treatment for the disorder typically involves managing the symptoms and preventing complications. This may include:
1. Avoiding arginine-rich foods in the diet
2. Providing supplemental nutrition to support growth and development
3. Managing seizures with anticonvulsant medications
4. Physical therapy to improve muscle tone and mobility
5. Supportive care to address cognitive and vision impairments
6. Dialysis or kidney transplantation in cases of advanced kidney disease
The prognosis for individuals with hyperargininemia varies depending on the severity of the disorder and the presence of any additional medical conditions. With appropriate management, many individuals with hyperargininemia are able to lead active and fulfilling lives. However, the disorder can be life-threatening in some cases, particularly if left untreated or if complications arise.
Arginase
D-arginase
METAP2
Argininemia
NOS1
ARG1 (gene)
Stanley Cohen (biochemist)
PEGylation
ARG2
Intestinal permeability
Homoarginine
Canavanine
Interleukin-13 receptor
Transition state analog
Urea cycle
Pirfenidone
FLOT2
Ureohydrolase
Macrophage-activating factor
Ethylenediaminetetraacetic acid
Manganese in biology
Manganese
Insulin-degrading enzyme
John Yudkin
Helicobacter pylori
Adipose tissue macrophages
Regulatory macrophages
Hyperammonemia
Ornithine
Canaline
Arginase deficiency: MedlinePlus Genetics
Arginase deficiency: MedlinePlus Genetics
talks.cam : T cell intrinsic role of Arginase 2 in modulating anti-tumor immunity
"Cattle Rumen Tissue Arginase and Molecular Weights of Its Subunits" by MİNE ERİŞİR and SEMA TEMİZER OZAN
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Publication Detail
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Biomarkers Search
Chromosome 6 - wikidoc
Involves elevated arginase1
- Obesity-induced vascular inflammation involves elevated arginase activity. (bvsalud.org)
ARG14
- Mutations in the ARG1 gene cause arginase deficiency. (medlineplus.gov)
- The ARG1 gene provides instructions for making an enzyme called arginase. (medlineplus.gov)
- Arginase-1, encoded by the ARG1 gene, is a cytosolic metalloenzyme expressed predominantly in hepatocytes which plays a key role in the urea cycle by catalyzing the hydrolysis of arginine to ornithine and urea. (femtopath.com)
- In addition to classical biomarkers, liver injury was assessed by cytokeratin 18 (CK18) cleaved form, high-mobility group box 1, arginase 1 (ARG1), microRNA 122 (miR-122), and glutamate dehydrogenase. (nih.gov)
Inhibitor2
- These effects of HFHS, except for weight gain and hyperglycemia , were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH). (bvsalud.org)
- To better evaluate this effect, we chronically administered an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and applied an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy. (nih.gov)
Enzyme4
- The molecular weight of native arginase, estimated by gel filtration on a Sephadex G-150 column, was 122 500 ± 2500 and those of subunits of the enzyme, estimated by SDS-PAGE and gel filtration on a Sephadex G-100 column, were 44 000 ± 1000 and 34 500 ± 500. (tubitak.gov.tr)
- Results: Arginase was found to have an alkaline pH optima(~9.5) with little enzyme activity at physiological pH. (medscimonit.com)
- Arginase (ARG), an enzyme implicated in many cardiovascular diseases, can compete with nitric oxide (NO) synthase for their common substrate, L-arginine. (elsevierpure.com)
- They have shown for the first time in a mouse model of tough-to-treat optic nerve trauma, that removing the enzyme arginase 2, which increases with injury, decreases neuron death in the retina as well as the degeneration of nerve fibers that connect neurons to each other and ultimately the brain. (nih.gov)
Deficiency8
- Arginase deficiency is an inherited disorder that causes the amino acid arginine (a building block of proteins) and ammonia to accumulate gradually in the blood. (medlineplus.gov)
- Arginase deficiency usually becomes evident by about the age of 3. (medlineplus.gov)
- In some affected individuals, signs and symptoms of arginase deficiency may be less severe, and may not appear until later in life. (medlineplus.gov)
- Arginase deficiency belongs to a class of genetic diseases called urea cycle disorders. (medlineplus.gov)
- In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. (medlineplus.gov)
- The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency. (medlineplus.gov)
- Hyperargininemia due to liver arginase deficiency. (medlineplus.gov)
- Sun A, Crombez EA, Wong D. Arginase Deficiency. (medlineplus.gov)
Hyperargininemia1
- examine the neurological changes associated with hyperargininemia using an arginase-1-deficient mouse. (jci.org)
Induces1
- Silica exposure induces arginase I expression in rat lung. (cdc.gov)
Ornithine2
- For instance, in non-cancerous cells arginine is synthesized in cells from citrulline via argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase in the urea cycle 8 , and metabolized by arginase 1 to produce urea and ornithine. (nature.com)
- Increased arginase can also provide ornithine for synthesis of polyamines via ornithine decarboxylase (ODC) and proline/collagen via ornithine aminotransferase (OAT), leading to vascular cell proliferation and collagen formation, respectively.We hypothesized that elevated arginase activity is involved in Ang II-induced arterial thickening, fibrosis, and stiffness and that limiting its activity can prevent these changes. (elsevierpure.com)
Hepatic2
- Anti-Arginase-1 is highly specific for hepatocytes, and is therefore a sensitive and specific marker of benign and malignant hepatic tumors. (femtopath.com)
- They find that dysmyelination occurs shortly after birth but can be corrected by restoring hepatic arginase-1 via adeno-associated virus-mediated gene delivery, suggested a potential therapeutic approach that merits further study. (jci.org)
Liver2
Enzymes1
- Manganese is a cofactor for many enzymes, including manganese superoxide dismutase, arginase, and pyruvate carboxylase [ 1 , 2 ]. (nih.gov)
Synthesis1
- However, arginase has failed to inhibit NO synthesis. (medscimonit.com)
Significance2
Tissue6
- The arginase was partially purified from cattle rumen tissue and its properties were investigated and thereafter compared with those of other tissue arginases. (tubitak.gov.tr)
- The presence of a single anionic form of arginase in cattle rumen tissue was demonstrated by DEAE-sephacel chromatography. (tubitak.gov.tr)
- Cattle rumen tissue arginase contains only one isoenzyme. (tubitak.gov.tr)
- Arginase isolated from cattle rumen tissue may be arginase A_4 or A_2 form when it is compared with those of other tissue arginase isoenzymes. (tubitak.gov.tr)
- ADI, unlike arginase, was effective in lowering extracellular arginine in tissue culture media and inhibit NO production by the murine macrophage cell line N-9 in response to gamma interferon and LPS stimulation. (medscimonit.com)
- MCTR3 reprograms arthritic monocytes to upregulate Arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis. (logosbio.com)
Activity4
- This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor -α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 ( IL-10 ), vascular cell adhesion molecule-1 ( VCAM-1 ), and intercellular adhesion molecule-1 ( ICAM-1 ) mRNA and protein in both VAT and ECs. (bvsalud.org)
- Limiting arginase activity is a possible therapeutic means of controlling obesity -induced vascular and VAT inflammation . (bvsalud.org)
- Level of arginase activity in peritoneal macrophages isolated from the transgenic mice also was also unchanged. (nih.gov)
- 1. Serum arginase activity in postsurgical monitoring of patients with colorectal carcinoma. (nih.gov)
Mice1
- Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. (nih.gov)
Studies1
- Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity -induced vascular dysfunction. (bvsalud.org)
Role1
- Useful to study the role of arginase II gene in endothelium. (nih.gov)
Mouse1
- The cover image shows restoration of basal dendritic arbors of layer V pyramidal tract neurons in an AAV-treated arginase-1-deficient mouse. (jci.org)
Levels1
- ADI had more than 1000 fold higher affinity for arginine (Km ~ 30 µM for ADI vs ~45 mM for arginase), and was able to lower arginine levels to a much greater extent than arginase. (medscimonit.com)
Cell1
- Material/Methods: The murine macrophage cell line N-9 was treated with either arginase or arginine deiminase to determine the effect on intracellular and extracellular arginine and nitric oxide production. (medscimonit.com)
People with arginase3
- In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. (medlineplus.gov)
- People with arginase deficiency may also have developmental delay, loss of developmental milestones, and intellectual disability. (nih.gov)
- People with Arginase deficiency may be placed on a very low-protein diet with the help of a registered metabolic dietitian. (nih.gov)
Called urea cycle dis1
- Arginase deficiency belongs to a class of genetic diseases called urea cycle disorders. (medlineplus.gov)
Deficiency usually2
- Arginase deficiency usually becomes evident by about the age of 3. (medlineplus.gov)
- If untreated, arginase deficiency usually progresses to severe spasticity, loss of ambulation, complete loss of bowel and bladder control, and severe intellectual disability. (nih.gov)
Induced Pluri1
- Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells. (medscape.com)
Competes2
- Arginase competes with eNOS for L-arginine and has been implicated in the endothelial dysfunction. (nih.gov)
- Arginase competes with NOS for L-arginine to produce urea and ornithine , limiting NO production . (bvsalud.org)
Inhibition2
- Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. (nih.gov)
- Furthermore, AGEs impair vascular function that can be reversed by arginase inhibition. (bvsalud.org)
Hyperammonemia1
- Arginase deficiency in untreated individuals is characterized by episodic hyperammonemia of variable degree that is infrequently severe enough to be life threatening or to cause death. (nih.gov)
Therapeutic Target1
- Therefore, AGEs may be pivotal in arginase deleterious effects in diabetic VD, providing a novel therapeutic target. (bvsalud.org)
Gene4
- Rescue of the Functional Alterations of Motor Cortical Circuits in Arginase Deficiency by Neonatal Gene Therapy. (medscape.com)
- Useful to study the role of arginase II gene in endothelium. (nih.gov)
- Interestingly, blood cell gene expression in the apoE-/- fed 60% fat showed an 11-fold increase in arginase II (AII) and no increase in arginase I (AI). (cdc.gov)
- Increased arginase gene expression in the blood and tissue (apoE-/- only) are likely associated with the development of atherosclerosis. (cdc.gov)
Amino acid2
- Arginase deficiency is an inherited disorder that causes the amino acid arginine (a building block of proteins) and ammonia to accumulate gradually in the blood. (medlineplus.gov)
- As stated previously, plasma arginine levels can be low under conditions of stress, for example following surgery, when this amino acid is excessively catabolized by arginase. (medscape.com)
Proteins1
- High levels of LDH appear to indirectly indicate that two other proteins, hemoglobin and arginase, have broken out of red blood cells. (nih.gov)
Genetic1
- Arginase deficiency is a genetic disease, which means that it is caused by one or more genes not working correctly. (nih.gov)
Conclusion2
- In conclusion, AGEs increase arginase activity probably through the ERK1/2/ p38 MAPK pathway due to increased arginase I expression. (bvsalud.org)
- In conclusion, increased circulating arginase activity and reduced arginine are likely the result of liver and/ or tissue injury. (cdc.gov)
Atherosclerosis1
- Therefore we studied systemic changes in arginase and arginine metabolism in a model of atherosclerosis. (cdc.gov)
Regulation1
- however, AGEs' role in arginase regulation is unknown. (bvsalud.org)
Severe1
- In some affected individuals, signs and symptoms of arginase deficiency may be less severe, and may not appear until later in life. (medlineplus.gov)
Symptoms1
- The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency. (medlineplus.gov)
Human2
- The human arginases and arginase deficiency. (medscape.com)
- 6. Arginase in human urogenital tumors. (nih.gov)
Expression2
- Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. (medscape.com)
- Immunodetection of arginase revealed MGA-induced protein expression for arginase I. In aortic rings, MGA pretreatment impaired acetylcholine (ACh)-induced vasorelaxation , which was reversed by ABH. (bvsalud.org)
Model1
- Better model system to study functional significance of arginase II. (nih.gov)