Disease relevance of ARG1

• We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft [1].
• Upregulation of vascular arginase in hypertension decreases nitric oxide-mediated dilation of coronary arterioles [2].

High impact information on ARG1

• Constitutive expression of arginase in microvascular endothelial cells counteracts nitric oxide-mediated vasodilatory function [3].
• Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines [4].
• RESULTS: In the control group, liver revascularization increased plasma arginase concentrations (+615%) and reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%) [5].
• BACKGROUND: The release of liver arginase after orthotopic liver transplantation (OLT) causes a deficiency of L-arginine and nitrite in the plasma [5].
• The activities of argininosuccinate synthase and arginase were increased by 4-fold and 50-100-fold, respectively, in enterocytes from post-weaning pigs compared with suckling pigs [6].

Chemical compound and disease context of ARG1

• These results suggest that NO-mediated dilation of coronary arterioles is inhibited in hypertension by an increase in arginase activity in EC, which limits l-arginine availability to NOS for NO production [2].

Biological context of ARG1

• The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min [1].
• 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 [7].
• 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 [7].
• The objective of this study was to quantify arginine catabolism via arginase and nitric oxide synthase pathways in the mammary tissue of sows on d 28 of lactation [8].
• BACKGROUND: Therapeutic use of supplemental arginine has been proposed as a safe and efficacious method to produce NO from nitric oxide synthase (NOS) and to produce proline and polyamines from arginase to improve wound healing [9].

Anatomical context of ARG1

• 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 [10].
• Proline oxidase and OAT, but not arginase, were present in allantoic and amniotic fluids for the production of ornithine (the immediate substrate for polyamine synthesis) [11].
• In enterocytes isolated from pig jejunum, L-arginine is metabolized to L-citrulline either directly or indirectly through the sequence of reactions catalysed by arginase and ornithine transcarbamylase [12].
• CONCLUSION: Although NO appears to be necessary for granulation tissue formation, early supplemental arginine may disturb the reciprocal regulation of NOS 2 and arginase, leading to the preferential metabolism of arginine to excess NO rather than ornithine, with consequent reductions in angiogenesis and granulation tissue formation [9].
• Arginase activity was roughly 10, 40 and 100 times greater in hepatic tissue than in renal cortex, renal medulla or intestinal mucosa, respectively, while hepatic ornithine transcarbamoylase (OTC) activity was about 15 times greater than the activity present in mucosa tissue [13].

Associations of ARG1 with chemical compounds

• Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations [1].
• The induction of arginase appears to be sufficient to account for the formation of urea from ammonia, glutamine and arginine in post-weaning pig enterocytes [6].
• A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels [1].
• 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 [10].
• The activities of arginase, argininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and pyrroline-5-carboxylate (P5C) synthase were measured [14].

Other interactions of ARG1

• The activities of carbamoylphosphate synthase-I (-45%), argininosuccinate synthase (-38%), argininosuccinate lyase (-23%), arginase (-27%), and glutaminase (-18%), but not of ornithine carbamoyltransferase, ornithine aminotransferase, or glutamate dehydrogenase were reduced in liver of ST-treated pigs [15].
• Placentae as well as amniotic and allantoic fluids were analyzed for arginase, proline oxidase, ornithine aminotransferase (OAT), ornithine decarboxylase (ODC), proline transport, concentrations of amino acids and polyamines, and polyamine synthesis using established radiochemical and chromatographic methods [11].
• Liver arginase (ARG, EC 3.5.3.1) and aspartate aminotransferase (AAT, EC 2.6.1.1) activities were then determined in organ samples taken at slaughter time [16].
• After slaughter, urea cycle enzyme activities (argininosuccinate synthetase, EC 6.3.4.5; argininosuccinate lyase, EC 4.3.2.1; and arginase, EC 3.5.3.1) were determined in liver homogenates [17].
• Genes identified in MLN and tonsils corresponded to serum amyloid A, arginase I, osteopontin, lysozyme, annexin I, and heat shock proteins, respectively [18].

Analytical, diagnostic and therapeutic context of ARG1

• Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism [1].
• Serum arginase activity increased considerably in these animals during experimental hepatic damage induced by oral administration of carbon tetrachloride [19].
• Immunohistochemistry showed that arginase expression was increased but NOS expression was decreased in arteriolar ECs of HT vessels [2].
• A liver-derived immunosuppressive factor is an arginase: identification and mechanism of immunosuppression [20].

References