Rat Liver Arginase: Kinetic Mechanism, Alternate Substrates, and Inhibitors

Reczkowski, Robert S.; Ash, David E.

doi:10.1006/abbi.1994.1276

Cited by 155 publications

(121 citation statements)

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“…On the other hand, the V max of arginase at physiological pH (approx. 1400 µmol\min per mg ; calculated for rat liver arginase from [221]) is more than 1000 times that of the NOS enzymes (approx. 1 µmol\min per mg [220]), indicating similar rates of substrate usage for NO synthesis at low arginine concentrations.…”

Section: Arginase and No Synthesismentioning

confidence: 97%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,452

2,036

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Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified

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Section: Arginase and No Synthesismentioning

confidence: 97%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,452

2,036

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“…All arginases exhibit higher catalytic activity with Mn 21 as a metal cofactor except the Helicobacter pylori (H. pylori), which shows higher activity with Co 21 . These proteins usually display optimum activity at an alkaline pH 9-11 (5,6). H. pylori, a human pathogen infects the stomach of half of the population worldwide and causes chronic active gastritis, which can lead to peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Biochemical studies on Helicobacter pylori arginase: Insight into the difference in activity compared to other arginases

Srivastava

2010

IUBMB Life

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SummaryArginase is a binuclear Mn 21 -metalloenzyme of urea cycle that catalyzes the conversion of L-arginine to L-ornithine and urea. Unlike other arginases, the Helicobacter pylori enzyme is selective for Co 21 , and has lower catalytic activity. To understand the differences in the biochemical properties as well as activity compared to other arginases, we carried out a detailed investigation of different metal reconstituted H. pylori arginases that includes steady-state kinetics, fluorescence measurement, pH-dependent and oligomerization assays. Unlike other arginases (except human at physiological pH), the Co 21 -and Mn 21 -reconstituted H. pylori enzymes exhibit cooperative mechanism of arginine hydrolysis, and undergo self-association and activation with increasing concentrations. Analytical gel-filtration assays in conjunction with the kinetic data showed that the protein exists as a mixture of monomer and dimer with monomer being the major form (other arginases exclusively exist as a trimer or hexamer) but the dimer is associated with higher catalytic activity. The proportion of dimer is found to decrease with increasing salt concentrations indicating that salt bridges play important roles in dimerization of the protein. Furthermore, the fluorescence measurement showed that Co 21 ions play an important role in the local tertiary structure of the protein than Mn 21 . This is consistent with the pH-dependent studies where the Co 21 -enzyme showed a single ionization compared to the double in the Mn 21 -enzyme. Thus, this study presents the detailed biochemical and spectroscopic investigations into the differences in the biochemical properties and activity between H. pylori and other arginases.

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“…Kaysen and Strecker (1973) reported that the K m value for kidney arginase was 18 mM, about two and a half times the K m value for liver arginase (6.8 mM). On the contrary, the K m value for rat liver arginase was found to be 1 ± 0.1 mM (Reczkowski and Ash, 1994). There were differences between the published K m values for rat liver and kidney arginases (Glass and Knox, 1973;Kaysen and Strecker, 1973;Tarrab et al, 1974;Spector et al, 1982;Jenkinson and Grigor 1994;Reczkowski and Ash, 1994).…”

Section: Discussionmentioning

confidence: 85%

“…On the contrary, the K m value for rat liver arginase was found to be 1 ± 0.1 mM (Reczkowski and Ash, 1994). There were differences between the published K m values for rat liver and kidney arginases (Glass and Knox, 1973;Kaysen and Strecker, 1973;Tarrab et al, 1974;Spector et al, 1982;Jenkinson and Grigor 1994;Reczkowski and Ash, 1994). This may be due to the variety of employed enzyme assays and to assay conditions that were not optimised.…”

Section: Discussionmentioning

confidence: 91%

“…Increased urea production in diabetes has been demonstrated in vivo, in liver slices, and in perfused livers (Green and Miller, 1960;McLean and Novello, 1965;Baxter and Schofield, 1980;Jorda et al, 1981). Both products (L-ornithine and urea) of the arginase reaction were inhibitors of arginase (Glass and Knox, 1973;Reczkowski and Ash, 1994). While K m for kidney arginase is unchanged, a marked decrease in V max may indicate enzyme inhibition (non-competitive) ( Figure 7B).…”

Section: Discussionmentioning

confidence: 91%

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Evaluation of optimal conditions for arginase activity in streptozotocin induced diabetic rats

Erişir¹,

Erçel²,

Yılmaz³

et al. 2005

Vet. Med. - Czech

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The assay conditions needed to achieve maximal activity of liver and kidney arginase in diabetic and non-diabetic rats were investigated and compared. The physicochemical and kinetic properties of liver arginase in diabetic and control rats were very similar, those of kidney arginase were significantly different. It was found that preincubation temperature (68°C), preincubation period (20 min), optimum pH (10.1) of liver arginase and Km (3.2) for its substrate, L-arginine, did not change in diabetic and non-diabetic rats. As a consequence of diabetes, the optimum Mn2+ concentration for liver arginase only changed from 1 to 2 mM. Although the preincubation temperature and period for activation of kidney arginase in control rats was unnecessary, they were found to be 56ºC and 12 min in diabetic rats. The pH profile of arginase in kidney of diabetic rats was different from that of control rats. The Km value (6.7) of arginase for L-arginine in kidney is unchanged in diabetes whereas a marked decrease in Vmax was found. Optimum Mn2+ concentration (2 mM) for kidney arginase was unchanged in diabetes. The activity of arginase in liver of diabetic animals was higher 1.5 to 1.7 times than that of controls. Diabetes caused an about 53% decrease of arginase activity in kidney of female rats, 26% in that of males. These findings may suggest an idea that encoded arginases by separate gene loci may be affected differently by the pathological and hormonal status.

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Rat Liver Arginase: Kinetic Mechanism, Alternate Substrates, and Inhibitors

Cited by 155 publications

References 0 publications

Arginine metabolism: nitric oxide and beyond

Arginine metabolism: nitric oxide and beyond

Biochemical studies on Helicobacter pylori arginase: Insight into the difference in activity compared to other arginases

Evaluation of optimal conditions for arginase activity in streptozotocin induced diabetic rats

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