Endogenous Metabolite from Microbe and Human

赖氨酸是一种l -氨基酸；赖氨酸的l -异构体。它具有作为微量营养素、营养保健品、抗惊厥药、大肠杆菌代谢物、酿酒酵母代谢物、植物代谢物、人类代谢物、藻类代谢物和小鼠代谢物的作用。它是一种天冬氨酸家族氨基酸、一种蛋白质原氨基酸、一种赖氨酸和一种l - α氨基酸。它是l -赖氨酸（1+）的共轭碱。它是l -赖氨酸的共轭酸。它是d -赖氨酸的对映体。它是l -赖氨酸两性离子和l -赖氨酸两性离子的互变异构体。 < br > 赖氨酸（Lysine）是一种α-氨基酸，化学式为HO2CCH(NH2)(CH2)4NH2。这种氨基酸是一种必需氨基酸，这意味着人类不能合成它。它的密码子是AAA和AAG。赖氨酸是一种碱基，精氨酸和组氨酸也是。ε-氨基在催化过程中作为氢结合位点和一般碱。常见的翻译后修饰包括ε-氨基甲基化，产生甲基赖氨酸、二甲基赖氨酸和三甲基赖氨酸。后者发生在钙调蛋白中。其他翻译后修饰包括乙酰化。胶原蛋白含有赖氨酸，它是由赖氨酸通过赖氨酸羟化酶产生的。内质网或高尔基体中赖氨酸残基的o -糖基化用于标记细胞分泌的某些蛋白质。

L-赖氨酸治疗可减少 L-精氨酸引起的胰腺组织损伤，并通过阻止炎症细胞因子 IL-6 的释放来增加抗氧化活性。 L-赖氨酸在治疗前后显着降低丙二醛和一氧化氮水平，而谷胱甘肽活性和抗氧化酶（过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶）显着增加[1]。补充 L-赖氨酸几乎完全缓解了血管钙化。在腺嘌呤大鼠中，膳食 L-赖氨酸显着抑制血浆完整甲状旁腺激素，同时促进健康的骨血管轴。 Lys 基团保留的股骨磷灰石方向进一步支持了 L-赖氨酸的骨保护特性。与赖氨酸相反，膳食 L-赖氨酸会提高血浆中脯氨酸、精氨酸、高精氨酸和丙氨酸的水平 [2]。随着 L-赖氨酸的胃排空半衰期延长至 4 分钟/克，在大鼠中观察到的剂量依赖性胃排空延迟也在人类中观察到。此外，注意到肠液积聚的增加呈剂量依赖性（0.4 mL/min/g L-赖氨酸）[3]。

Four groups of mice (10 in each group) were assessed. Group I was the control. Animals in groups II-IV were injected intraperitoneally with L-arginine hydrochloride (400 mg/kg body weight [bw]) for 3 days. Group III animals were orally pre-treated with L-lysine (10 mg/kg bw), whereas group IV animals were orally post-treated with L-lysine (10 mg/kg bw). Serum samples were subjected to amylase, lipase, transaminase, and interleukin-6 (IL-6) assays. The pancreas was excised to measure the levels of malondialdehyde, nitric oxide, catalase, superoxide dismutase, reduced glutathione, and glutathione peroxidase.[1]

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L-lysine doses from 0-800 mg in rats and 0.5-7.5 g in humans were analyzed for their effect on gastric emptying and GI secretion. Human GI function was assessed non-invasively using magnetic resonance imaging (MRI), rat data were acquired using standard lethal measurement methods. L-lysine dose dependently delayed gastric emptying and stimulated GI secretion in rats as reflected by residual phenol red content and increased gastric wet weight.[2]

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Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.[3]

Absorption, Distribution and Excretion
Absorption
Absorbed from the lumen of the small intestine into the enterocytes by an active transport process

Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. /Amino acids/

After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond-specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/

Protein secretion into the intestine continues even under conditions of protein-free feeding, and fecal nitrogen losses (ie, nitrogen lost as bacteria in the feces) may account for 25% of the obligatory loss of nitrogen. Under this dietary circumstance, the amino acids secreted into the intestine as components of proteolytic enzymes and from sloughed mucosal cells are the only sources of amino acids for the maintenance of the intestinal bacterial biomass. ... Other routes of loss of intact amino acids are via the urine and through skin and hair loss. These losses are small by comparison with those described above, but nonetheless may have a significant impact on estimates of requirements, especially in disease states. /Amino acids/

About 11 to 15 g of nitrogen are excreted each day in the urine of a healthy adult consuming 70 to 100 g of protein, mostly in the form of urea, with smaller contributions from ammonia, uric acid, creatinine, and some free amino acids. These are the end products of protein metabolism, with urea and ammonia arising from the partial oxidation of amino acids. Uric acid and creatinine are indirectly derived from amino acids as well. The removal of nitrogen from the individual amino acids and its conversion to a form that can be excreted by the kidney can be considered as a two-part process. The first step usually takes place by one of two types of enzymatic reactions: transamination or deamination. Transamination is a reversible reaction that uses ketoacid intermediates of glucose metabolism (e.g., pyruvate, oxaloacetate, and alpha-ketoglutarate) as recipients of the amino nitrogen. Most amino acids can take part in these reactions, with the result that their amino nitrogen is transferred to just three amino acids: alanine from pyruvate, aspartate from oxaloacetate, and glutamate from alpha-ketoglutarate. Unlike many amino acids, branched-chain amino acid transamination occurs throughout the body, particularly in skeletal muscle. Here the main recipients of amino nitrogen are alanine and glutamine (from pyruvate and glutamate, respectively), which then pass into the circulation. These serve as important carriers of nitrogen from the periphery (skeletal muscle) to the intestine and liver. In the small intestine, glutamine is extracted and metabolized to ammonia, alanine, and citrulline, which are then conveyed to the liver via the portal circulation. Nitrogen is also removed from amino acids by deamination reactions, which result in the formation of ammonia. A number of amino acids can be deaminated, either directly (histidine), by dehydration (serine, threonine), by way of the purine nucleotide cycle (aspartate), or by oxidative deamination (glutamate). ... Glutamate is also formed in the specific degradation pathways of arginine and lysine. Thus, nitrogen from any amino acid can be funneled into the two precursors of urea synthesis, ammonia and aspartate. /Amino acids/

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Metabolism / Metabolites
Hepatic
Like other amino acids, the metabolism of free lysine follows two principal paths: protein synthesis and oxidative catabolism. It is required for biosynthesis of such substances as carnitine, collage, and elastin.

Oxidative deamination or transamination of l-lysine /yields/ alpha-keto-epsilon-aminocaproic acid; decarboxylation of l-lysine /yields/ cadaverine. /From table/

Once the amino acid deamination products enter the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle or Krebs cycle) or the glycolytic pathway, their carbon skeletons are also available for use in biosynthetic pathways, particularly for glucose and fat. Whether glucose or fat is formed from the carbon skeleton of an amino acid depends on its point of entry into these two pathways. If they enter as acetyl-CoA, then only fat or ketone bodies can be formed. The carbon skeletons of other amino acids can, however, enter the pathways in such a way that their carbons can be used for gluconeogenesis. This is the basis for the classical nutritional description of amino acids as either ketogenic or glucogenic (ie, able to give rise to either ketones [or fat] or glucose). Some amino acids produce both products upon degradation and so are considered both ketogenic and glucogenic. /Amino acids/

... Rates of lysine metabolism in fetal sheep during chronic hypoglycemia and following euglycemic recovery /were compared with/ results with normal, age-matched euglycemic control fetuses to explain the adaptive response of protein metabolism to low glucose concentrations. Restriction of the maternal glucose supply to the fetus lowered the net rates of fetal (umbilical) glucose (42%) and lactate (36%) uptake, causing compensatory alterations in fetal lysine metabolism. The plasma lysine concentration was 1.9-fold greater in hypoglycemic compared with control fetuses, but the rate of fetal (umbilical) lysine uptake was not different. In the hypoglycemic fetuses, the lysine disposal rate also was higher than in control fetuses due to greater rates of lysine flux back into the placenta and into fetal tissue. The rate of CO2 excretion from lysine decarboxylation was 2.4-fold higher in hypoglycemic than control fetuses, indicating greater rates of lysine oxidative metabolism during chronic hypoglycemia. No differences were detected for rates of fetal protein accretion or synthesis between hypoglycemic and control groups, although there was a significant increase in the rate of protein breakdown (p < 0.05) in the hypoglycemic fetuses, indicating small changes in each rate. This was supported by elevated muscle specific ubiquitin ligases and greater concentrations of 4E-BP1. Euglycemic recovery after chronic hypoglycemia normalized all fluxes and actually lowered the rate of lysine decarboxylation compared with control fetuses (p < 0.05). These results indicate that chronic hypoglycemia increases net protein breakdown and lysine oxidative metabolism, both of which contribute to slower rates of fetal growth over time. Furthermore, euglycemic correction for 5 days returns lysine fluxes to normal and causes an overcorrection of lysine oxidation.

Toxicity Summary
Proteins of the herpes simplex virus are rich in L-arginine, and tissue culture studies indicate an enhancing effect on viral replication when the amino acid ratio of L-arginine to L-lysine is high in the tissue culture media. When the ratio of L-lysine to L-arginine is high, viral replication and the cytopathogenicity of herpes simplex virus have been found to be inhibited. L-lysine may facilitate the absorption of calcium from the small intestine.

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Health Effects
Chronically high levels of lysine are associated with at least 5 inborn errors of metabolism including: D-2-Hydroxyglutaric Aciduria, Familial Hyperlysinemia I, Hyperlysinemia II, Pyruvate carboxylase deficiency and Saccharopinuria.

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Exposure Routes
Absorbed from the lumen of the small intestine into the enterocytes by an active transport process

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Interactions
Lysine 10 mmol/kq given to mice for 1 to 10 days significantly increased clonic and tonic seizure latencies caused by 60 mg/kg pentylenetetrazol (PTZ). On day 1 the clonic and tonic seizure latencies were increased from 160.4 +/- 26.3 and 828.6 +/- 230.8 s to 286.1 +/- 103.3 and 982.3 +/- 98.6 respectively. Both clonic and tonic seizure latencies increased steadily with additional L-lysine treatment without significant change in survival rate. On day 10, the anticonvulsant effect reached its highest level with a block of tonic seizures and survival rate of 100% without tolerance developing. Acute L-lysine significantly increased the mean clonic latency from 85.8 +/- 5.24 to 128.2 +/- 9.0 s and the mean tonic seizure from 287.2 +/- 58.7 to 313.5 +/- 42.2 s with 80 mg/kg of PTZ. On day 10 of treatment, the anticonvulsant effect of L-lysine was highest, with a significant incr of 155 and 184% in clonic and tonic latencies over control, respectively. After 15 and 20 day treatment, clonic and tonic seizure latencies and survival rate decreased, suggesting development of tolerance ... PMID:8385623

Acute intake of high levels of lysine interferes with dietary protein metabolism and competes with the transport of arginine, suggesting that adverse effects from high levels of lysine are more likely to occur if protein intake or dietary arginine intake is low.

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rat LD50 oral 11400 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 23(1253), 1981
rat LD50 intraperitoneal 3700 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 23(1253), 1981
rat LD50 subcutaneous 4 gm/kg Iyakuhin Kenkyu. Study of Medical Supplies., 12(933), 1981
rat LD50 intravenous 2850 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 23(1253), 1981
mouse LD50 oral 13400 mg/kg Gekkan Yakuji. Pharmaceuticals Monthly., 23(1253), 1981

[1]. Suppression of acute pancreatitis by L-lysinein mice. BMC Complement Altern Med. 2015 Jun 23;15:193.

[2]. L-lysine dose dependently delays gastric emptying and increases intestinal fluid volume in humans and rats. Neurogastroenterol Motil. 2014 Jul;26(7):999-1009.

[3]. Dietary L-lysineprevents arterial calcification in adenine-induced uremic rats. J Am Soc Nephrol. 2014 Sep;25(9):1954-65.

L-lysine hydrochloride is the hydrochloride salt of L-lysine It contains a L-lysine.
An essential amino acid. It is often added to animal feed.
See also: Lysine (has active moiety) ... View More ...

C6H15CLN2O2

182.64

182.082

C, 39.46; H, 8.28; Cl, 19.41; N, 15.34; O, 17.52

657-27-2

L-Lysine;56-87-1;L-Lysine-15N2 hydrochloride;1217460-44-0;L-Lysine-13C6,15N2 hydrochloride;1200447-00-2;L-Lysine-d9 hydrochloride;2708343-64-8;L-Lysine-d4 hydrochloride;284664-96-6;L-Lysine hydrate;39665-12-8;L-Lysine-13C6,15N2,d9 dihydrochloride;1994268-57-3;L-Lysine-13C dihydrochloride;202190-50-9;L-Lysine-d8 hydrochloride;344298-93-7;L-Lysine-13C6 hydrochloride;1228077-86-8;L-Lysine acetate;57282-49-2

69568

White to off-white solid powder

311.5ºC at 760 mmHg

263 °C (dec.)(lit.)

142.2ºC

1.729

89.34

4

4

5

11

106

1

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

BVHLGVCQOALMSV-JEDNCBNOSA-N

InChI=1S/C6H14N2O2.ClH/c7-4-2-1-3-5(8)6(9)10;/h5H,1-4,7-8H2,(H,9,10);1H/t5-;/m0./s1

(2S)-2,6-diaminohexanoic acid;hydrochloride

Lysine HCl; L-Lysine monohydrochloride; L-Lysine hydrochloride; 657-27-2; L-Lysine monohydrochloride; L-Lysine, monohydrochloride; lysine hydrochloride; Lyamine; 10098-89-2; H-Lys-OH.HCl; Lysine hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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 (~547.50 mM)
DMSO :< 1 mg/mL

配方 1 中的溶解度: 50 mg/mL (273.75 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：
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