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PubMed2004

Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction.

BACKGROUND: Arginase competes with endothelial nitric oxide synthase (eNOS) for the substrate l-arginine and decreases NO production. This study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis. METHODS AND RESULTS: In human endothelial cells isolated from umbilical veins, thrombin concentration- and time-dependently stimulated arginase enzymatic activity, reaching a 1.9-fold increase (P<0.001) at 1 U/mL for 24 hours. The effect of thrombin was prevented by C3 exoenzyme or the HMG-CoA reductase inhibitor fluvastatin, which inhibit RhoA, or by the ROCK inhibitors Y-27632 and HA-1077. Adenoviral expression of constitutively active RhoA or ROCK mutants enhanced arginase activity (approximately 3-fold, P<0.001), and the effect of active RhoA mutant was inhibited by the ROCK inhibitors. Neither thrombin nor the active RhoA/ROCK mutants affected arginase II protein level, the only isozyme detectable in the cells. Moreover, a significantly higher arginase II activity (1.5-fold, not the protein level) and RhoA protein level (4-fold) were observed in atherosclerotic aortas of apoE-/- compared with wild-type mice. Interestingly, l-arginine (1 mmol/L), despite a significantly higher eNOS expression in aortas of apoE-/- mice, evoked a more pronounced contraction, which was reverted to a greater vasodilation by the arginase inhibitor l-norvaline (20 mmol/L) compared with the wild-type animals (n=5, P<0.001). CONCLUSIONS: Thrombin enhances arginase activity via RhoA/ROCK in human endothelial cells. Higher arginase enzymatic activity is involved in atherosclerotic endothelial dysfunction in apoE-/- mice. Targeting vascular arginase may represent a novel therapeutic possibility for atherosclerosis.

Animals↗

PubMed2005

Increased arginase activity in cystic fibrosis airways.

RATIONALE: Airway nitric oxide concentrations are reduced in cystic fibrosis (CF). Arginases compete for L-arginine, the substrate of nitric oxide synthesis. OBJECTIVES: We hypothesized that increased arginase activity may be one factor contributing to nitric oxide deficiency in CF. MEASUREMENTS: We therefore studied sputum arginase activity, exhaled nitric oxide, and pulmonary function in patients with cystic fibrosis. RESULTS: Mean (+/- SEM) sputum arginase activity was significantly higher in patients admitted for pulmonary exacerbation compared with patients with stable disease (1.032 +/- 0.148 vs. 0.370 +/- 0.091 U/mg protein, p = 0.004). Fourteen days of intravenous antibiotic treatment resulted in significantly decreased sputum arginase activity in all patients (p = 0.0002). However, arginase activity was still significantly (p = 0.0001) higher in CF sputum after treatment for exacerbation compared with induced sputum from healthy control subjects (0.026 +/- 0.006 U/mg protein). Negative correlations were found for sputum arginase activity at admission with FEV1 (r = -0.41, p = 0.01), as well as changes in arginase activity with percent change in FEV1 during antibiotic therapy (r = -0.4, p < 0.01) in CF. Exhaled nitric oxide in CF was positively correlated to FEV1 (r = 0.34, p = 0.007), and in patients admitted for pulmonary exacerbation negatively correlated to sputum arginase activity (r = -0.45, p = 0.03). CONCLUSIONS: These data suggest that increased sputum arginase activity contributes to nitric oxide deficiency in CF lung disease and may be relevant in the pathogenesis of CF airway disease.

Adolescent↗

PubMed2002

Decreased expression of arginase II in the kidneys of Dahl salt-sensitive rats.

Arginase catalyzes the hydrolysis of arginine to urea and ornithine. Urea is not only an important solute for concentrating urine but also inhibits Na-K-2Cl cotransport. To elucidate the roles of arginase in the development of salt-sensitive hypertension, we examined arginase activity and expression in the kidney and other organs of Dahl/Rapp salt-sensitive (SS) and salt-resistant (SR) rats before and after 4 weeks' administration of a 4% NaCl or control diet. At 4 weeks of age, arginase activity in the kidney was lower in SS rats than in SR rats. Kidney arginase activity was lower in SS rats than in SR rats at 8 weeks of age, and salt loading did not alter arginase activity. Arginase II (the dominant isoform in the kidney) mRNA and protein in the kidney of salt-loaded SS rats were also lower than those of salt-loaded SR rats. Arginase activities in the liver and cerebellum did not differ between SS and SR rats. To examine the effect of urea, the product of arginase reaction, on the development of hypertension, SS rats were given a 4% NaCl diet containing 5% kaolin or 5% urea. Six-week urea supplementation attenuated the development of hypertension in SS rats. These findings suggest that decreased arginase expression in the kidney may be at least partially responsible for the salt-sensitive hypertension in SS rats.

Animals↗

PubMed2000

Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells.

L-Arginine is the common substrate for two enzymes, arginase and nitric oxide synthase (NOS). Arginase converts L-arginine to L-ornithine, which is the precursor of polyamines, which are essential components of cell proliferation. NOS converts L-arginine to produce NO, which inhibits proliferation of many cell lines. Various human breast cancer cell lines were initially screened for the presence of arginase and NOS. Two cell lines, BT-474 and MDA-MB-468, were found to have relatively high arginase activity and very low NOS activity. Another cell line, ZR-75-30, had the highest NOS activity and comparatively low arginase activity. The basal proliferation rates of MDA-MB-468 and BT-474 were found to be higher than the ZR-75-30 cell line. N-Hydroxy-L-arginine (NOHA), a stable intermediate product formed during conversion of L-arginine to NO, inhibited proliferation of the high arginase-expressing MDA-MB-468 cells and induced apoptosis after 48 h. NOHA arrested these cells in the S phase, increased the expression of p21, and reduced spermine content. These effects of NOHA were not observed in the ZR-75-30 cell line, which expresses high NOS and relatively low arginase. The effects of NOHA were antagonized in the presence of L-ornithine (500 microM), which suggests that in MDA-MB-468 cell line, the arginase pathway is very important for cell proliferation. Inhibition of the arginase pathway led to depletion of intracellular spermine and apoptosis as observed by terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling assay and induction of caspase 3. In contrast, the ZR-75-30 cell line maintained its viability and its L-ornithine and spermine levels in the presence of NOHA. We conclude that NOHA has antiproliferative and apoptotic actions on arginase-expressing human breast cancer cells that are independent of NO.

Apoptosis↗

PubMed1983

Purification of rat kidney arginases A1 and A4 and their subcellular distribution.

Arginase A1 and arginase A4 were isolated from rat kidney. Arginase A4, which is the main form of arginase in rat kidney, was obtained at a highly purified preparation; its specific activity was 1057 mumoles ornithine . min-1 . mg-1 protein. The two forms differed in subcellular localization. Form A1 was restricted to the cytosol while form A4 occurred mainly in the mitochondrial matrix. Kidney arginases A1 and A4 were found to differ in immunological properties. Kidney arginase A1, in contrast to arginase A4, precipitated with antibodies against arginase A1 from rat liver. Arginase A1 from kidney was shown to differ from arginase A1 from the liver. The two enzymes could be distinguished by double diffusion test and immunoelectrophoresis.

Animals↗

PubMed1963

Studies of the mechanism of action of the Shope rabbit papilloma virus. I. Concerning the nature of the induction of arginase in the infected cells.

These studies make plain that the Shope papilloma virus induces the production of an arginase in rabbit squamous epithelium, and provide evidence that the information for the synthesis of the enzyme is derived from the virus rather than the rabbit. This form of induction is therefore different from that brought about by chemicals such as galactosides (36). Striking differences were shown between the physiochemical properties of Shope virus-induced arginase and other arginases of domestic and Kansas cottontail rabbits. The absence of a requirement for manganese suggests the mechanism of splitting off urea from arginine by papilloma arginase probably differs from that of previously described arginases. These findings (particularly the experiments in which it was demonstrated that papilloma growth could be greatly reduced by giving animals supplemental arginine in the presence of small amounts of the arginase inhibitor, canavanine) provide evidence that suggests the following mechanism of action for the virus: viral DNA introduces into rabbit epithelium the information for the synthesis of an arginase for which the cells have no control mechanism. The arginase depletes cellular arginine and, in turn, the synthesis of arginine-rich nuclear histones (2), thereby freeing the nucleus for greater synthetic activity (4, 35), which results in more rapid growth of the papilloma cells. Domestic rabbit papillomas induced with purified virus derived from wild rabbit papillomas were shown to contain an antigen which reacts immunologically like a wild rabbit antigen. It was distinct from the arginase, the protein coat of the virus, and the Vx-2 antigen. The presence of the wild rabbit antigen seems indicative of integration of the virus DNA in the host genome of the wild rabbit. Other incidental findings include the description of a simple method, accurate to within 1 per cent, for determining the partial specific volume of a protein, and the description of a modification of the Richards and Schachman method (9) enabling the determination of the molecular weight and homogeneity of a protein with as little as 0.25 mg and with an accuracy of 2 per cent.

Animals↗

PubMed2002

Serum arginase activity in postsurgical monitoring of patients with colorectal carcinoma.

BACKGROUND: Colorectal carcinoma (CRC) is one of the most common malignancies. In the current work, the role of arginase as a diagnostic marker in patients with recurrent CRC and colorectal liver metastases (CRCLM) was studied. METHODS: Arginase activity was monitored in serum from 40 patients with primary CRC and from 100 patients with CRCLM. Blood was taken before and after patients underwent tumor resection. Studies were conducted for 3 years. RESULTS: Preoperative arginase activity in serum from patients with CRC and CRCLM was much greater compared with the arginase activity in serum from healthy control blood donors. One and two cut-off levels of increased arginase activity were observed in patients with CRC and CRCLM, respectively. After patients underwent tumor resection, the arginase activity decreased to normal values in both patients with CRC and patients with CRCLM. Activity levels remained low in patients who did not develop recurrent CRC or CRCLM (first or second). In patients who developed subsequent recurrences or metastases that appeared after surgery, during 3 years of surveillance, a significant rise in serum arginase activity was observed. The clinical prognosis for patients was worst when the postoperative serum arginase activity was very high, because those patients more often developed second liver metastases or died. CONCLUSIONS: The authors conclude that the determination of serum arginase activity may be a complementary test to confirm the occurrence of CRC and may be useful for the early diagnosis of patients who develop recurrent CRC and/or CRCLM.

Adenocarcinoma↗

PubMed1996

Immunohistochemical study of arginase in cancer of the stomach.

High levels of arginase have been detected in gastric adenocarcinoma. To examine the hypothesis that this is due to macrophage infiltration into the tumour, we localized the cellular distribution of arginase by immunohistochemical staining. We examined gastric adenocarcinomas and their corresponding normal tissues (n = 45), leiomyomas (n = 2), leiomyosarcomas (n = 3), human gastric adenocarcinoma cell lines (n = 3), and benign gastric ulcers (n = 4) by the avidin-biotin-peroxidase complex technique. Macrophages with strong arginase immunoreactivity were observed infiltrating both gastric normal and cancer tissues. No arginase immunoreactivity was observed in normal mucosal gland, muscular and serosal tissues or benign gastric ulcers. The immunoreactivity of arginase was positive but heterogeneous in most specimens of gastric adenocarcinoma (62.2%) and was absent from gastric intestinal metaplasia, leiomyomas and leiomyosarcomas. Among the 28 neoplasms with arginase immunoreactivity, scattered immunoreactivity was also noted in adjacent dysplastic glands in 12 (42.8%) specimens. Arginase immunoreactivity was observed in all three gastric cancer cell lines. Arginase is present in the cytoplasm but not in the nucleus. These data suggest that the high arginase levels in adenocarcinoma cancer tissues originate largely from cancer cells.

Adenocarcinoma↗

PubMed2003

Glucocorticoid inhibition of interleukin-4 (IL-4) and interleukin-13 (IL-13) induced up-regulation of arginase in rat airway fibroblasts.

Arginase appears to play a significant role in the pathogenesis of inflammatory and obstructive airway diseases by interfering with NO synthesis (hyperreactivity) and by providing substrate for collagen synthesis (remodelling). IL-4 and IL-13 are key proinflammatory cytokines in asthma, and their effects on arginase in rat primary airway fibroblasts in culture were studied. Airway fibroblasts showed significant arginase activity, which was higher when the culture medium contained 10% fetal calf serum (FCS) (20 mU/mg protein) compared to 5% FCS (6 mU/mg protein). In presence of 10% FCS addition of IL-4 or IL-13 (10 ng/ml each) for 20 h or 40 h caused an increase in arginase activity by 76% and 160% (IL-4) and by 134% and 213% (IL-13), respectively. Using RT-PCR mRNA for arginase I was clearly detectable with 30 PCR cycles, whereas mRNA for arginase II was hardly detectable with 35 PCR cycles. IL-4 and IL-13 caused a clear increase in the mRNA of both arginase isoenzymes. Dexamethasone (1 microM) did not affect basal arginase activity, but largely opposed the stimulatory effects of IL-4 and IL-13. In conclusion, IL-4 and IL-13 can cause a marked up-regulation of arginase activity in rat airway fibroblasts and these effects can be inhibited by glucocorticoids.

Animals↗

PubMed1986

Studies on L-arginase in developing rat small intestine, brain, and kidney. II. Effect of hydrocortisone and thyroxine.

The influences of hydrocortisone and thyroxine on the developmental changes of arginase activity in intestine, kidney, and brain of suckling rats were studied. A single injection of hydrocortisone (50 mg/kg) into rats aged 9 days evoked premature increase of jejunal arginase activity due to precocious formation of arginase A4. Arginase A4 can be detected about 48 hr after hydrocortisone injection, whereas in intact rats the enzyme appears in the intestinal mucosa on the 19th-21st days of postnatal life. After hydrocortisone administration to rats aged 6 days, a similar pattern of arginase activity in jejunum was observed. Under the same conditions, the influence of hydrocortisone on kidney arginase was weaker. The hormone did not have any influence on the activity of brain arginase. Daily injection of thyroxine (2 mg/kg) to 6-day-old rats (for 6 consecutive days) caused a precocious increase of the arginase activity in intestine. Under the same conditions, only a slight increase of the arginase activity was observed in kidney, whereas in brain the activity was unaffected.

Aging↗

PubMed2006

Identification of arginase in human placental villi.

l-Arginine is the common substrate for arginase and nitric oxide synthase (NOS). Arginase converts l-arginine to urea and ornithine, which is the principal precursor for production of polyamines required for cell proliferation. Human placenta expresses endothelial NOS (eNOS) in syncytiotrophoblasts, but the expression of arginase has not been fully elucidated. Our aim was to investigate the expression and distribution patterns of arginase-I (A-I) and arginase-II (A-II) in human placental villi in the first trimester and at term using immunohistochemistry, RT-PCR and Western blot analysis. The arginase enzyme activity in placental villi was also measured. Immunohistochemistry showed different distribution patterns of the arginase isoforms during gestation: A-I was observed only in cytotrophoblasts, while A-II was observed in both cytotrophoblasts and syncytiotrophoblasts. RT-PCR and Western blot analysis showed expression of A-I and A-II in the first trimester and at term in human placental villi. Expression of A-II and arginase activity was greater in the first trimester than at term. Differentiation of cytotrophoblasts into syncytiotrophoblasts may be associated with l-arginine metabolism through modulation of l-arginine availability for eNOS and A-I. And elevated arginase activity in the early gestational period may be responsible for proliferation of trophoblasts by increasing polyamines production. These results suggest that the l-arginine-ornithine-polyamine and l-arginine-nitric oxide pathways play a role in placental growth and development.

Arginase↗

PubMed1996

Myometrial arginase activity increases with advancing pregnancy in the guinea pig.

OBJECTIVES: Arginase has been suggested to play an important role in cellular growth and development, particularly important to the fetus, by supplying L-ornithine for the synthesis of polyamines. The purpose of this investigation was to determine whether pregnancy alters myometrial arginase activity and whether estradiol was responsible for the change. STUDY DESIGN: Myometrium and kidney were obtained from nonpregnant and pregnant guinea pigs of known gestational age. Arginase activity was measured under physiologic conditions by the conversion carbon 14-labeled guanidino-L-arginine to carbon 14-labeled urea. The concentrations of the enzyme's substrate, L-arginine, and its principal metabolite, L-ornithine, were measured in myometrium from near-term pregnant animals by use of an amino acid analyzer. Finally, a group of random cycle guinea pigs received 500 microgram/kg estradiol for 5 days before the myometrium was removed. RESULTS: Myometrial arginase activity in pregnant animals was more than double that of myometrium from nonpregnant animals by the time the first measurement was made at 0.14 gestation. It continued to rise, peaking at values >25-fold higher than the nonpregnant activity by 0.90 gestation. Arginase activity in the myometrium underlying the placental implantation site was >25 fold higher (p<0.05) than myometrium from nonpregnant animals when first studied at 0.63 gestation and 10-fold higher than the contralateral fundal myometrium at the same time of gestation. Myometrial arginase activity in the sterile horn of six pregnant animals was half that of the horn containing one or more pups, but still five times higher than that of nonpregnant animals. Renal arginase activity also rose with advancing pregnancy, but the magnitude of the increase (up to 2-fold) was much smaller than that observed in either the fundal or placental implantation site myometrium. Estradiol had no significant effect on myometrial arginase activity. CONCLUSIONS: These studies demonstrate that pregnancy increases myometrial arginase activity and that the presence of placenta or fetus is necessary for the maximal effect.

Animals↗

PubMed1998

Alpha-difluoromethylornithine (DFMO) as a potent arginase activity inhibitor in human colon carcinoma cells.

Alpha-difluoromethylornithine (DFMO) is commonly used as a specific ornithine decarboxylase (ODC, EC4.1.1.17) irreversible inhibitor. ODC is the enzyme responsible for polyamine biosynthesis, which has been shown to be strictly necessary for cell proliferation. In HT-29 Glc-/+ cells, L-arginine is the major precursor of these molecules through the sequential actions of arginase, which leads to L-ornithine generation and ODC. L-ornithine, a substrate for ODC, retroinhibits arginase. Since DFMO is an ornithine analogue, we searched for a direct effect of this agent upon arginase. The flux of L-arginine through arginase in intact cells was inhibited by 51+/-11% by 10 mM of DFMO whereas 10 mM of L-valine, a known potent arginase inhibitor, inhibited this flux by 73+/-6%. DFMO equilibrated between extracellular and intercellular spaces and, when used at 10-mM concentration, was without effect on L-arginine net uptake. Measurement of arginase activity in HT-29 cell homogenates with increasing concentrations of DFMO and L-arginine led to an inhibition with a calculated Ki (inhibitory constant) equal to 3.9+/-1.0 mM. L-ornithine was less effective than DFMO in inhibiting arginase activity. Bovine liver arginase, used as another source of the enzyme, was also severely inhibited by DFMO. The inhibitory effect of DFMO upon arginase, one step upstream of the ODC reaction in the metabolic conversion of L-arginine to polyamines, is of potential physiological importance, since it could alter the production of ornithine and thus its metabolism in pathways other than the ODC pathway.

Animals↗

PubMed1999

Induction of intracellular arginase activity does not diminish the capacity of macrophages to produce nitric oxide in vitro.

The hypothesis was tested that induction of arginase expression in macrophages (M phi) diminishes nitric oxide (NO) synthesis due to intracellular competition between arginase and inducible nitric oxide synthase (iNOS) for L-arginine (L-arg). Murine M phi cell lines and bone marrow-derived M phi (BMM) were stimulated to express either iNOS or arginase or to co-express these two enzymes. The response pattern obtained was complex but allowed the following conclusions: (i) iNOS and arginase are differentially regulated. (ii) High intracellular arginase levels do not limit the capacity of M phi to synthesize NO even when the L-arg concentration in the culture medium is lowered to physiological levels. (iii) Arginase levels in BMM pre-exposed to either M phi colony-stimulating factor (M-CSF) or granulocyte-M phi colony-stimulating factor (GM-CSF) differ markedly, but iNOS expression and NO synthesis by the two BMM types is similar. (iv) Regulation of iNOS and arginase differs between primary murine bone marrow M phi and murine M phi cell lines. (v) Arginase activity appears to be inhibited during high-output NO synthesis. Taken together, our results show that NO production by M phi is not compromised by conditions that increase intracellular arginase activity.

Animals↗

PubMed2001

Classical and slow-binding inhibitors of human type II arginase.

Arginases catalyze the hydrolysis of L-arginine to yield L-ornithine and urea. Recent studies indicate that arginases, both the type I and type II isozymes, participate in the regulation of nitric oxide production by modulating the availability of arginine for nitric oxide synthase. Due to the reciprocal regulation between arginase and nitric oxide synthase, arginase inhibitors have therapeutic potential in treating nitric oxide-dependent smooth muscle disorders, such as erectile dysfunction. We demonstrate the competitive inhibition of the mitochondrial human type II arginase by N(omega)-hydroxy-L-arginine, the intermediate in the reaction catalyzed by nitric oxide synthase, and its analogue N(omega)-hydroxy-nor-L-arginine, with K(i) values of 1.6 microM and 51 nM at pH 7.5, respectively. We also demonstrate the inhibition of human type II arginase by the boronic acid-based transition-state analogues 2(S)-amino-6-boronohexanoic acid (ABH) and S-(2-boronoethyl)-L-cysteine (BEC), which are known inhibitors of type I arginase. At pH 7.5, both ABH and BEC are classical, competitive inhibitors of human type II arginase with K(i) values of 0.25 and 0.31 microM, respectively. However, at pH 9.5, ABH and BEC are slow-binding inhibitors of the enzyme with K(i) values of 8.5 and 30 nM, respectively. The findings presented here indicate that the design of arginine analogues with uncharged, tetrahedral functional groups will lead to the development of more potent inhibitors of arginases at physiological pH.

Aminocaproates↗

PubMed2002

Arginase in glomerulonephritis.

l-Arginine is converted to nitric oxide and citrulline by the enzyme nitric oxide synthase (NOS). Its in vivo inhibition has led to the revelation of a multitude of diverse, often conflicting functions in the inflammatory melee. l-Arginine is also converted to ornithine and urea by the enzyme arginase as a part of the hepatic urea cycle. However, a more holistic interpretation of the two pathways and the associated metabolism (summarized in Fig. 1) has led to its reassessment as a pathologically significant enzyme. This is reflected by the continued increase over the past five years of the number of publications discussing both nitric oxide and arginase. The strong association between inflammation and high arginase and NOS activity is epitomized by immune complex-induced glomerulonephritis and other glomerulonephritides. Arginase is encoded by two recently discovered genes (Arginase I and Arginase II). There is now substantial evidence for an interaction between both arginase isoforms and all three NOS isoforms in pathological situations. This review considers the relationship between Arginases I and II and the inflammation-associated isoform of NOS called NOS II. In particular, it consolidates the current understanding of arginase and associated metabolic pathways, and highlights some of the issues that are often overlooked in such studies.

Animals↗

PubMed2001

Significance of arginase and ornithine in malignant tumors of the human skin.

During neoplastic development, several aspects of the regulation of polyamine synthesis undergo profound changes. In extrahepatic mammalian tissues in which the urea cycle is not functioning, arginase is believed to supply the cell with ornithine, a non-protein amino acid that is a precursor for biosynthesis of polyamines. Because the activity of ornithine decarboxylase and polyamine levels have been shown to be elevated during carcinogenesis, we decided to investigate the role of arginase in the development of malignant tumors of the human skin and to examine whether arginase activity and ornithine level can be used as biologic markers for distinguishing patients with squamous cell cancer from patients with basal cell cancer. For this purpose, we studied tissue arginase activity and ornithine level in tumor and adjacent normal tissues in 16 patients (55 +/- 10 years of age) with malignant skin tumors (8 of which were squamous cell cancers and 8 of which were basal cell cancers). The mean arginase activity and ornithine levels in tumor tissues (total) were 17.75 +/- 8.54 U/mg protein and 40.89 +/- 14.88 nmol/mg protein, respectively, versus 3.69 +/- 1.71 U/mg protein and 12.98 +/- 6.21 nmol/mg protein, respectively, for normal tissues. The mean specific arginase activity levels in squamous cell and basal cell cancers of the human skin were 18.49 +/- 10.47 U/mg protein and 16.63 +/- 6.00 U/mg protein, respectively. The mean ornithine levels in squamous cell and basal cell cancers of the human skin were 42.45 +/- 19.10 nmol/mg protein and 39.33 +/- 10.19 nmol/mg protein, respectively. Our results indicated that (1) arginase activity and ornithine levels are elevated in squamous cell and basal cell cancers of the human skin; (2) the increased activity of arginase and hence the elevated levels of ornithine may be important in the development of malignant tumors of the human skin; and (3) although arginase activity and ornithine level may be useful for distinguishing patients with malignant skin tumors from healthy subjects, they cannot be used as biologic markers for distinguishing patients with squamous cell cancer from patients with basal cell cancer.

Arginase↗

PubMed2001

Allosteric inhibition of rat liver and kidney arginase by copper and mercury ions.

Two isozyme forms of arginase are found in the rat. All arginases are metalloenzymes which require manganese for activity. Many arginases are activated by cobalt and nickel ions and inhibited by heavy metal ions. The purpose of this study was to compare the effect of other heavy metal ions on the rat liver isozyme (arginase I) and the rat kidney isozyme (arginase II). The activation and inhibition of arginase I and II by metal ions were different. However, both isozymes were strongly inhibited by cupric and mercuric ions. The inhibition of arginase I by cupric and mercuric ions was increased greatly by preincubation of the enzyme with the metal ions. However, preincubation of arginase II by cupric and mercuric ions had little effect on the inhibition of the enzyme. Under certain conditions the kinetics of the inhibition of both arginases I and II by cupric and mercuric ions was nonlinear allosteric.

Allosteric Regulation↗