Microbial Metabolite; Endogenous Metabolite

α-氨基酸包括精氨酸。 L 型氨基酸是二十种最常见的天然氨基酸之一。在分子遗传学方面，三联体CGU、CGC、CGA、CGG、AGA和AGG是蛋白质合成过程中编码精氨酸的核苷酸碱基或密码子。这些碱基存在于信使核糖核酸 (mRNA) 的结构中。根据个体的发育阶段和整体健康状况，精氨酸被归类为哺乳动物中的条件必需氨基酸或半必需氨基酸。在患有严重脓毒症的个体中，L-精氨酸与较低的心脏指数有关，但中风指数没有变化。 L-精氨酸组中 40% 的人以及安慰剂组中 24% 的人休克在 72 小时内消退。接受长期辛伐他汀治疗（每天皮下注射 2 毫克/公斤，持续 14 天）后，L-精氨酸（15 分钟内 450 毫克/公斤）可促进大脑 eNOS 的绝对上调，并放大和维持大脑充血 (38%)。 SV-129 小鼠的血流。

L-精氨酸可用于动物建模，建立动物胰腺炎模型。L -精氨酸是内皮型一氧化氮合酶（eNOS）产生NO的底物，可代谢为一氧化氮（NO）、多胺或l -脯氨酸，刺激炎症。l -精氨酸还能选择性地破坏胰腺腺泡细胞，导致急性坏死性胰腺炎。 雄性大鼠单次腹腔注射l -精氨酸500 mg /100 g体重时，胰腺腺泡细胞被选择性破坏，朗格汉斯胰岛未见形态学改变。早在注射后24小时，嗜碱性细胞丧失，酶原脱颗粒，腺泡细胞空泡和坏死改变。3天后，成纤维细胞活性明显，胰腺小叶萎缩明显。早期电镜发现内质网改变，如池池部分扩张或空泡化，通常伴有附着在膜上的核糖体的丢失。精氨酸过量的影响可能归因于氨基酸的不平衡和随后的腺泡细胞中蛋白质合成的减少。在本研究过程中，胰腺周围、附睾、大网膜和腹膜后区域的脂肪组织均可见脂肪坏死伴明显白细胞浸润。这种变化与胰腺的明显坏死密切相关。血液中的脂肪酶水平也有所增加。[4]

Nitric oxide, a product of nitric oxide synthase activity, relaxes vascular smooth muscle and elevates brain blood flow. We evaluated the importance of eNOS to cerebral blood flow augmentation after L-arginine infusion and increases in flow after eNOS upregulation in SV-129 mice. Blood flow was measured by laser-Doppler flowmetry before and after L-arginine infusion (450 mg/kg during a 15-minute period) or measured by 14C-iodoamphetamine indicator fractionation or 14C-iodoantipyrine tissue equilibration techniques. rCBF increased by 26% (laser Doppler flowmetry) after L-arginine infusion but did not change in mutant mice deficient in eNOS expression. After eNOS upregulation by chronic simvastatin treatment (2 mg/kg subcutaneously, daily for 14 days), L-arginine amplified and sustained the hyperemia (38%) and increased absolute brain blood flow from 86 +/- 7 to 119 +/- 10 mL/100 g per minute. Furthermore, pretreatment with simvastatin enhanced blood flow within ischemic brain tissue after middle cerebral artery occlusion. Together, these findings suggest that eNOS activity is critical for blood flow augmentation during acute L-arginine infusion, and chronic eNOS upregulation combined with L-arginine administration provides a novel strategy to elevate cerebral blood flow in the normal and ischemic brain.[3]

Absorption
Absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.

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Metabolism / Metabolites
Some metabolism of L-arginine takes place in the enterocytes. L-arginine not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized.

rat LD50 oral 12 gm/kg BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX); BEHAVIORAL: ATAXIA; LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Pharmaceutical Sciences., 62(49), 1973 [PMID:4734197]
rat LD50 intraperitoneal 3793 mg/kg BEHAVIORAL: COMA; LUNGS, THORAX, OR RESPIRATION: DYSPNEA Archives of Biochemistry and Biophysics., 58(253), 1955 [PMID:13259702]
child LDLo intravenous 3900 mg/kg/30M BRAIN AND COVERINGS: OTHER DEGENERATIVE CHANGES; CARDIAC: OTHER CHANGES Journal of Toxicology, Clinical Toxicology., 35(621), 1997 [PMID:9365430]

[1]. Administration of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Crit Care Med. 2004 Jan;32(1):1-12.

[2]. I. Arginine. Biomed Pharmacother. 2002 Nov;56(9):439-45.

[3]. Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment. J Cereb Blood Flow Metab. 2000 Apr;20(4):709-17.

[4]. Effects of injecting excess arginine on rat pancreas. J Nutr. 1984 Mar;114(3):467-71.

[5]. Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice. Heliyon. 2019 Aug 27;5(8):e02222.

Arginine hydrochloride is a L-alpha-amino acid.
Arginine Hydrochloride is the hydrochloride salt form of arginine, an essential amino acid in juvenile humans. Arginine is a complex amino acid, often found at active sites in proteins and enzymes due to its amine-containing side chain. Arginine may prevent or treat heart and circulatory diseases, combat fatigue, and stimulate the immune system. It also boosts production of nitric oxide, relaxing blood vessels, and treating angina and other cardiovascular problems. Arginine is also an important intermediate in the urea cycle and in detoxification of nitrogenous wastes. (NCI04)
An essential amino acid that is physiologically active in the L-form.

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Mechanism of Action
Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

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Pharmacodynamics
Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.

C6H15CLN4O2

210.66

210.088

C, 34.21; H, 7.18; Cl, 16.83; N, 26.60; O, 15.19

1119-34-2

DL-Arginine;7200-25-1;L-Arginine-15N2 hydrochloride;204633-92-1;L-Arginine-15N4 hydrochloride;204633-95-4;L-Arginine-d7 hydrochloride;204244-77-9;L-Arginine-13C6 hydrochloride;201740-91-2;L-Arginine-13C6,15N4 hydrochloride;202468-25-5;L-Arginine butanoate;80407-72-3;L-Arginine-1-13C hydrochloride;2483735-41-5;L-Arginine-13C6,15N4,d7 hydrochloride;2483829-29-2;L-Arginine-1,2-13C2 hydrochloride;201740-75-2;L-Arginine-13C hydrochloride;94740-43-9;L-Arginine-15N4,d7 hydrochloride

66250

White to off-white solid powder

1.42

409.1ºC at 760 mmHg

226-230 °C(lit.)

201.2ºC

1.354

125.22

5

4

5

13

176

1

C(C[C@@H](C(=O)O)N)CN=C(N)N.Cl

KWTQSFXGGICVPE-WCCKRBBISA-N

InChI=1S/C6H14N4O2.ClH/c7-4(5(11)12)2-1-3-10-6(8)9;/h4H,1-3,7H2,(H,11,12)(H4,8,9,10);1H/t4-;/m0./s1

(2S)-2-amino-5-(diaminomethylideneamino)pentanoic acid;hydrochloride

NSC-203450; NSC203450; L-Arginine hydrochloride; 1119-34-2; Arginine Hydrochloride; L-ARGININE HCL; L-Arginine monohydrochloride; Arginine HCl; H-Arg-OH.HCl; R-Gene;NSC 203450; Arginine HCl; Detoxargin; Levargin; Arginine Hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~474.70 mM)
DMSO :< 1 mg/mL

配方 1 中的溶解度: 100 mg/mL (474.70 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。