L-亮氨酸 (10 mM) 处理会损害内分泌祖细胞的生长 [1]。在E13.5支架外植体中，不添加L-亮氨酸，Ngn3 mRNA水平在培养1天后增加，在前3天达到峰值，然后下降。添加 L-亮氨酸后，NGN3 mRNA 水平显着降低。 Ngn3 mRNA水平的下降与表达Ngn3的细胞数量的下降平行（4728±408 vs. 959±28；P<0.01）。最后，L-亮氨酸还对三个基因的 mRNA 水平产生剂量依赖性抑制作用，即 Ngn3、其靶标 Insm1 和胰岛素 [1]。亮氨酸通过增强 mTORC1 的激活来刺激新生猪肌肉中的蛋白质合成。 L-亮氨酸增加细胞内 HIF-1α 并激活过量的 HIF-1α 信号传导，这两者均由 mTOR 信号传导引导。该过程导致 Ngn3 抑制，从而降低 β 细胞水平 [1]。 L-亮氨酸通过刺激涉及光模板的基于磷脂的机制，刺激 mTORC1 GTP 激活蛋白上的 mTORC1 tRNA 合酶促进活性[2]。

在饮食诱导肥胖 (DIO) 小鼠中，白藜芦醇（12.5 mg/kg 饮食）加亮氨酸（24 g/kg 饮食）可增强脂肪 Sirt1 活性 [2]。联合使用时，可大大降低小鼠体重。

Animal/Disease Models: Sixweeks old male C57/BL6 black mouse (high-fat feed plus fat-induced obesity) [1]
Doses: 24 g Weight gain, visceral adipose tissue mass, fat oxidation and Thermogenesis[2]. /kg diet; Resveratrol (low dose; 12.5 mg/kg diet) dosing: 6 weeks
Experimental Results: Combination treatment with resveratrol (low dose; 12.5 mg/kg diet) resulted in weight gain, body weight gain, and visceral fat There is a significant reduction in tissue mass, fat oxidation and thermogenesis, and an associated decrease in respiratory exchange ratio (RER), particularly during the dark (feeding) cycle.

Absorption, Distribution and Excretion
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.
Table: Comparison of the Pool Sizes of Free and Protein-Bound Amino Acids in Rat Muscle [Table#7489]

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Metabolism / Metabolites
The branched-chain amino acids (BCAA) -- leucine, isoleucine, and valine -- differ from most other indispensable amino acids in that the enzymes initially responsible for their catabolism are found primarily in extrahepatic tissues. Each undergoes reversible transamination, catalyzed by a branched-chain aminotransferase (BCAT), and yields alpha-ketoisocaproate (KIC, from leucine), alpha-keto-beta-methylvalerate (KMV, from isoleucine), and alpha-ketoisovalerate (KIV, from valine). Each of these ketoacids then undergoes an irreversible, oxidative decarboxylation, catalyzed by a branchedchain ketoacid dehydrogenase (BCKAD). The latter is a multienzyme system located in mitochondrial membranes. The products of these oxidation reactions undergo further transformations to yield acetyl CoA, propionyl CoA, acetoacetate, and succinyl CoA; the BCAA are thus keto- and glucogenic.
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/
Kinetics of leucine and its oxidation were determined in human pregnancy and in the newborn infant, using stable isotopic tracers, to quantify the dynamic aspects of protein metabolism. These data show that in human pregnancy there is a decrease in whole-body rate of leucine turnover compared with nonpregnant women. In addition, data in newborn infants show that leucine turnover expressed as per kg body weight is higher compared with adults. The administering of nutrients resulted in a suppression of the whole-body rate of proteolysis ... The relations among the transamination of leucine, leucine N kinetics, and urea synthesis and glutamine kinetics in human pregnancy and newborn infants /were also examined/. In human pregnancy, early in gestation, there is a significant decrease in urea synthesis in association with a decrease in the rate of transamination of leucine. A linear correlation was evident between the rate of leucine reamination and urea synthesis during fasting in pregnant and nonpregnant women. In healthy-term newborn and growing infants, although the reamination of leucine was positively related to glutamine flux, leucine reamination was negatively related to urea synthesis, suggesting a redirection of amino N toward protein accretion ...
The metabolic disease 3-methylglutaconic aciduria type I (MGA1) is characterized by an abnormal organic acid profile in which there is excessive urinary excretion of 3-methylglutaconic acid, 3-methylglutaric acid and 3-hydroxyisovaleric acid. Affected individuals display variable clinical manifestations ranging from mildly delayed speech development to severe psychomotor retardation with neurological handicap. MGA1 is caused by reduced or absent 3-methylglutaconyl-coenzyme A (3-MG-CoA) hydratase activity within the leucine degradation pathway. The human AUH gene has been reported to encode for a bifunctional enzyme with both RNA-binding and enoyl-CoA-hydratase activity. In addition, it was shown that mutations in the AUH gene are linked to MGA1 ...
For more Metabolism/Metabolites (Complete) data for L-Leucine (8 total), please visit the HSDB record page.

Toxicity Summary
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates. The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic. There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

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Interactions
... High dietary levels of leucine suppressed the growth of rats fed a low protein diet, and the growth suppression could be prevented by supplementation with isoleucine and valine.
It has been well established that the branched chain amino acids (BCAA) compete with other large neutral amino acids (LNAA, particularly tryptophan and tyrosine) for membrane transport. Although the BCAA do not act as direct precursors for neurotransmitters, they can affect transport of certain LNAA across the blood-brain barrier, and thereby influence central nervous system concentrations of certain neurotransmitters.
Diets supplemented with glutamine, glutamine plus dihydroxyacetone, and glutamine plus dihydroxyacetone plus leucine were administered to male Sprague-Dawley rats for 1 wk. These are combinations that have been shown to stimulate hepatic glycogen synthesis in vitro. Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, rats were fed a test meal and injected with 3H2O to measure in vivo rates of glycogen and lipid synthesis. Positional analysis of the 3H incorporated into glycogen was used to determine the proportion of glycogen synthesized via pyruvate. Final levels of plasma glucose and triacylglycerol and hepatic glycogen were also measured. Dietary glutamine increased hepatic glycogen synthesis. Addition of dihydroxyacetone, with or without additional leucine, caused an additional increase in hepatic glycogen synthesis and increased the proportion of glycogen synthesized via pyruvate. Lipogenesis was not altered in the liver or adipose tissue. None of the dietary treatments had any effect on food intake, but the diets that contained dihydroxyacetone decreased the rate of weight gain ...
Aging is characterized by a progressive loss of muscle mass that could be partly explained by a defect in the anabolic effect of food intake. ... This defect resulted from a decrease in the protein synthesis response to leucine in muscles from old rats. ... /This/ study assessed the effect of antioxidant supplementation on leucine-regulated protein metabolism in muscles from adult and old rats. Four groups of 8 and 20 mo old male /Wistar/ rats were supplemented or not for 7 wk with an antioxidant mixture containing rutin, vitamin E, vitamin A, zinc, and selenium. At the end of supplementation, muscle protein metabolism was examined in vitro using epitrochlearis muscles incubated with increasing leucine concentrations. In old rats, the ability of leucine to stimulate muscle protein synthesis was significantly decreased compared with adults. This defect was reversed when old rats were supplemented with antioxidants. It was not related to increased oxidative damage to 70-kDa ribosomal protein S6 kinase that is involved in amino acid signaling. These effects could be mediated through a reduction in the inflammatory state, which decreased with antioxidant supplementation ...
For more Interactions (Complete) data for L-Leucine (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 5379 mg/kg

[1]. Baoshan Xu, et al. Stimulation of mTORC1 with L-leucine rescues defects associated with Roberts syndrome. PLoS Genet. 2013;9(10):e1003857.
[2]. Bruckbauer A, et al. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2012 Aug 22;9(1):77.
[3]. Rachdi L, et al. L-leucine alters pancreatic β-cell differentiation and function via the mTor signaling pathway. Diabetes. 2012 Feb;61(2):409-17.

Therapeutic Uses
Branched chain amino acid (BCAA)-enriched protein or amino acid mixtures and, in some cases, BCAA alone, have been used in the treatment of a variety of metabolic disorders. These amino acids have received considerable attention in efforts to reduce brain uptake of aromatic amino acids and to raise low circulating levels of BCAA in patients with chronic liver disease and encephalopathy. They have also been used in parenteral nutrition of patients with sepsis and other abnormalities.
/Experimental Therapy/ There have been several reports of clinical trials in which groups of healthy humans, in most cases trained athletes, were given high doses of leucine by intravenous infusion. Most of the studies involved a single dose of the amino acid. These trials measured physical and mental performance, the impact on blood levels of other amino acids, and in one case, of insulin and glucose output.
/Experimental Therapy/ This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of L-[ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 +/- 0.005%/hr; post-EAA: 0.063 +/- 0.007%/hr) and the 41% (basal: 0.036 +/- 0.004%/hr; post-EAA: 0.051 +/- 0.007%/hr) Leu young groups (p < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 +/- 0.003%/hr; post-EAA: 0.049 +/- 0.006%/hr; p > 0.05) but did increase following ingestion of 41% Leu EAA (basal: 0.038 +/- 0.007%/hr; post-EAA: 0.056 +/- 0.008%/hr; p < 0.05). Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved (p < 0.05) in all groups, with the exception of the 26% Leu elderly group ... Increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects.
/Experimental Therapy/ The objective was to assess the effect of 3 mo of leucine supplementation on muscle mass and strength in healthy elderly men. Thirty healthy elderly men with a mean (+/- SEM) age of 71 +/- 4 yr and body mass index (BMI; in kg/m(2)) of 26.1 +/- 0.5 were randomly assigned to either a placebo-supplemented (n = 15) or leucine-supplemented (n = 15) group. Leucine or placebo (2.5 g) was administered with each main meal during a 3-mo intervention period. Whole-body insulin sensitivity, muscle strength (one-repetition maximum), muscle mass (measured by computed tomography and dual-energy X-ray absorptiometry), myosin heavy chain isoform distribution, and plasma amino acid and lipid profiles were assessed before, during, and/or after the intervention period. No changes in skeletal muscle mass or strength were observed over time in either the leucine- or placebo-supplemented group. No improvements in indexes of whole-body insulin sensitivity (oral glucose insulin sensitivity index and the homeostasis model assessment of insulin resistance), blood glycated hemoglobin content, or the plasma lipid profile were observed.

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Drug Warnings
Although some evidence of reduced muscle catabolism and clear evidence of an impact on blood concentrations of other amino acids (most especially, declines in the other branched chain amino acid (BCAA) and several other neutral amino acids) can be found in these /clinical trial/ reports, none of these provides evidence of an adverse effect of leucine.
Long-term leucine supplementation (7.5 g/day) does not augment skeletal muscle mass or strength and does not improve glycemic control or the blood lipid profile in healthy elderly men.

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Pharmacodynamics
An essential amino acid. (Claim) Leucine helps with the regulation of blood-sugar levels, the growth and repair of muscle tissue (such as bones, skin and muscles), growth hormone production, wound healing as well as energy regulation. It can assist to prevent the breakdown of muscle proteins that sometimes occur after trauma or severe stress. It may also be beneficial for individuals with phenylketonuria - a condition in which the body cannot metabolize the amino acid phenylalanine

C6H13NO2

131.17

131.094

61-90-5

L-Leucine-d10;106972-44-5;L-Leucine-13C;74292-94-7;L-Leucine-d2;362049-59-0;L-Leucine-13C6;201740-84-3;Leucine-13C6;L-Leucine-15N;59935-31-8;L-Leucine-1-13C,15N;80134-83-4;L-Leucine-13C6,15N;202406-52-8;L-Leucine-d3;87828-86-2;L-Leucine-18O2;73579-45-0;L-Leucine-d;89836-93-1;L-Leucine-15N,d10;L-Leucine-d7;92751-17-2;L-Leucine-2-13C;201612-66-0;L-Leucine-2-13C,15N;285977-88-0

6106

White glistening hexagonal plates from aqueous alcohol
White crystals

1.0±0.1 g/cm3

225.8±23.0 °C at 760 mmHg

286-288 ºC

90.3±22.6 °C

0.0±0.9 mmHg at 25°C

1.463

0.73

63.32

2

3

3

9

101

1

O([H])C([C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])[H])=O

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InChI=1S/C6H13NO2/c1-4(2)3-5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t5-/m0/s1

(2S)-2-amino-4-methylpentanoic acid

Leucinum; FEMA No. 3297; Leucine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

H2O : ~8.33 mg/mL (~63.51 mM)

配方 1 中的溶解度: 6.25 mg/mL (47.65 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 超声助溶 (<60°C).

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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；
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7、 以上所有助溶剂都可在 Invivochem.cn网站购买。