L-缬氨酸 | 72-18-4

• 物质功能分类: 生物化工 - 常见氨基酸及蛋白质类
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: L-缬氨酸
• 中文别名: L-2-氨基-3-甲基丁酸；異戊胺酸；L-穿心排草氨基；L-2-氨基异戊酸；2-氨基-3-甲基丁酸；缬氨酸
• 英文名称: L-valine
• 英文别名: valine；Val；L-Val；(2S)-2-amino-3-methylbutanoic acid；H-Val-OH；(S)-2-amino-3-methylbutanoic acid；(S)-(–)-valine；(S)-valine；V；(2S)-2-amino-3-methylbutanoate;hydron
• CAS: 72-18-4
• 化学式: C₅H₁₁NO₂
• 分子量: 117.148
• InChiKey: KZSNJWFQEVHDMF-BYPYZUCNSA-N

物化性质

• 熔点：
  295-300 °C (subl.) (lit.)
• 比旋光度：
  28 º (c=8, 6N HCl)
• 沸点：
  213.6±23.0 °C(Predicted)
• 密度：
  1.23
• 溶解度：
  在水中的溶解度25 mg/mL
• 最大波长(λmax)：
  λ: 260 nm Amax: 0.15λ: 280 nm Amax: 0.1
• LogP：
  0.29
• 物理描述：
  Solid
• 颜色/状态：
  Leaflets from water + alcohol
• 蒸汽压力：
  5.55X10-9 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation: +22.9 deg at 23 °C/D (c = 0.8 in 20% HCl). Molecular rotation: + 33.1 deg at at sodium line (5N HCl); + 72.6 deg at sodium line (glacial acetic acid)
• 分解：
  When heated to decomposition, it emits toxic fumes of /nitric oxides/.
• 解离常数：
  pKa = 2.30
• 碰撞截面：
  134.28 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]
• 稳定性/保质期：

  存在于烤烟和白肋烟烟叶以及烟气中。

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

支链氨基酸（BCAA）——亮氨酸、异亮氨酸和缬氨酸——与大多数其他必需氨基酸的不同之处在于，最初负责它们分解的酶主要存在于肝外组织中。每一种氨基酸都会经历可逆的转氨作用，由支链氨基酸转移酶（BCAT）催化，并产生α-酮异己酸（KIC，来自亮氨酸）、α-酮-β-甲基戊酸（KMV，来自异亮氨酸）和α-酮异戊酸（KIV，来自缬氨酸）。这些酮酸然后经历不可逆的氧化脱羧作用，由支链酮酸脱氢酶（BCKAD）催化。后者是一个位于线粒体膜上的多酶系统。这些氧化反应的产物会进一步转化为乙酰辅酶A、丙酰辅酶A、乙酰乙酸和琥珀酰辅酶A；因此，BCAA是生酮和生糖的。

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.

来源:Hazardous Substances Data Bank (HSDB)

代谢

一旦氨基酸脱氨产物进入三羧酸循环（也称为柠檬酸循环或克雷布斯循环）或糖酵解途径，它们的碳骨架也可用于生物合成途径，特别是用于葡萄糖和脂肪的生成。氨基酸的碳骨架是形成葡萄糖还是脂肪取决于其进入这两个途径的点。如果它们作为乙酰辅酶A进入，那么只能形成脂肪或酮体。然而，其他氨基酸的碳骨架可以以这样的方式进入途径，即它们的碳可用于糖异生。这是将氨基酸经典营养描述为生酮或生糖（即能够产生酮体[或脂肪]或葡萄糖）的基础。一些氨基酸在降解时产生这两种产物，因此被认为是既生酮又生糖的。/氨基酸/

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/

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 对富含星形胶质细胞的原代培养（APC）在U-(13)C-缬氨酸的分解代谢过程中产生的(13)C标记代谢物进行了核磁共振（NMR）分析，并随后释放到培养介质中。所呈现的结果显示，APC（1）能够有效地处理培养介质中含有的缬氨酸；（2）能够将缬氨酸降解为三羧酸（TCA）循环成员琥珀酰辅酶A；并且（3）将缬氨酸的分解产物及其衍生物，如U-(13)C-2-氧异戊酸、U-(13)C-3-羟基异丁酸、U-(13)C-2-甲基丙二酸、[U-(13)C]异丁酸和[U-(13)C]丙酸，以及包括乳酸在内的几种TCA循环依赖性代谢物释放到细胞外环境中。

... An NMR analysis was performed to identify the (13)C-labeled metabolites that are generated by astroglia-rich primary cultures (APC) during catabolism of U-(13)C-valine and that are subsequently released into the incubation medium. The results presented show that APC (1) are potently disposing of the valine contained in the incubation medium; (2) are capable of degrading valine to the tricarboxylic acid (TCA) cycle member succinyl-CoA; and (3) release into the extracellular milieu valine catabolites and compounds generated from them such as U-(13)C-2-oxoisovalerate, U-(13)C-3-hydroxyisobutyrate, U-(13)C-2-methylmalonate, [U-(13)C]isobutyrate, and [U-(13)C]propionate as well as several TCA cycle-dependent metabolites including lactate.

来源:Hazardous Substances Data Bank (HSDB)

代谢

支链氨基酸（BCAAs）的代谢在培养的小脑星形胶质细胞中超滤系统中进行了研究，使用的是标记有(15)N的亮氨酸、异亮氨酸或缬氨酸。一些培养物暴露在谷氨酸脉冲（50微摩尔；每2分钟10秒；总共75分钟）下，以模拟谷氨酸能突触活动期间的条件。从(15)N-亮氨酸、(15)N-异亮氨酸或(15)N-缬氨酸到细胞内谷氨酸的(15)N掺入量约为40-50%，各个BCAAs之间的差异很小。有趣的是，当暴露在外源谷氨酸中时，来自(15)N-缬氨酸的谷氨酸中的标记(%)并没有减少，这与(15)N-亮氨酸或(15)N-异亮氨酸中的标记(%)显著减少形成了对比。这表明在重复暴露于谷氨酸期间，仅涉及缬氨酸的转氨作用被上调。可以推测，缬氨酸特别是作为神经元和星形胶质细胞区间转移的氨基酸，可能具有一个重要的功能，这个功能可能会在突触活动期间被上调。

... Metabolism of branched-chain amino acids (BCAAs) was investigated in cultured cerebellar astrocytes in a superfusion paradigm employing (15)N-labeled leucine, isoleucine, or valine. Some cultures were exposed to pulses of glutamate (50 uM; 10 sec every 2 min; 75 min in total) to mimic conditions during glutamatergic synaptic activity ... Incorporation of (15)N into intracellular glutamate from (15)N-leucine, (15)N-isoleucine, or (15)N-valine amounted to about 40-50% and differed only slightly among the individual BCAAs. Interestingly, label (%) in glutamate from (15)N-valine was not decreased upon exposure to exogenous glutamate, which was in contrast to a marked decrease in labeling (%) from (15)N-leucine or (15)N-isoleucine. This suggests an up-regulation of transamination involving only valine during repetitive exposure to glutamate. It is suggested that valine in particular might have an important function as an amino acid translocated between neuronal and astrocytic compartments, a function that might be up-regulated during synaptic activity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

适用于缬氨酸、亮氨酸和异亮氨酸。
这一组必需氨基酸被确定为支链氨基酸，即BCAAs。由于这种碳原子排列人类无法制造，这些氨基酸是饮食中的基本要素。这三种化合物的分解起始于肌肉，并产生NADH和FADH2，这些可以用于生成ATP。这三种氨基酸的分解在前两个步骤中使用相同的酶。每种情况的第一步是使用单一BCAA转氨酶进行转氨，以α-酮戊二酸作为氨基受体。结果，产生了三种不同的α-酮酸，并使用共同的支链α-酮酸脱氢酶进行氧化，产生了三种不同的辅酶A衍生物。随后，代谢途径发生分歧，产生了许多中间产物。
缬氨酸的主要产物是丙酰辅酶A，是琥珀酰辅酶A的糖原前体。异亮氨酸的分解以乙酰辅酶A和丙酰辅酶A的产生结束；因此，异亮氨酸既是糖原性的也是酮原性的。亮氨酸产生乙酰辅酶A和乙酰乙酰辅酶A，因此被归类为严格的酮原性。
存在一些与BCAAs错误分解相关的遗传疾病。最常见的缺陷是在支链α-酮酸脱氢酶中。由于这三种氨基酸只有一个脱氢酶酶，所有三种α-酮酸都会积累并从尿液中排出。这种疾病被称为枫糖尿症，因为受影响的个体的尿液具有特征性的气味。这些情况下的智力迟钝是严重的。不幸的是，由于这些是必需氨基酸，它们不能在饮食中大量限制；最终，受影响个体的寿命短暂，发育异常。主要的神经系统问题是由于中枢神经系统中髓鞘形成不良。

(Applies to Valine, Leucine and Isoleucine) <br/>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. <br/>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. <br/>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.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

从小肠通过一个钠依赖性的主动运输过程被吸收。

Absorbed from the small intestine by a sodium-dependent active-transport process.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

低血糖的症状。

Symptoms of hypoglycemia.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

高亮氨酸的饮食水平抑制了喂食低蛋白饮食的大鼠的生长，而这种生长抑制可以通过补充异亮氨酸和缬氨酸来预防。

... 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.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

从小肠通过一个钠依赖性的主动运输过程被吸收。

Absorbed from the small intestine by a sodium-dependent active-transport process.

来源:DrugBank

吸收、分配和排泄

血液和组织中的支链氨基酸（BCAA）浓度会受到多种疾病和异常生理状态的影响，包括糖尿病、肝功能不全、饥饿、蛋白质-卡路里营养不良、酗酒和肥胖。这些情况有时会导致血浆中BCAA池的剧烈变化。/氨基酸/

Blood and tissue concentrations of branched chain amino acids (BCAA) are altered by several disease and abnormal physiological states, including diabetes mellitus, liver dysfunction, starvation, protein-calorie malnutrition, alcoholism, and obesity. These and other conditions sometimes produce drastic alterations in plasma pools of BCAA. /Amino acids/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尽管溶解在体液中的游离氨基酸仅占身体氨基酸总质量的很小一部分，但它们对身体蛋白质的营养和代谢控制非常重要。尽管血浆部分最容易取样，但大多数氨基酸在组织细胞内池中的浓度更高。通常，大的中性氨基酸，如亮氨酸和苯丙氨酸，基本上与血浆处于平衡状态。其他一些氨基酸，尤其是谷氨酰胺、谷氨酸和甘氨酸，在细胞内池中的浓度是血浆中的10到50倍。饮食变化或病理状态可能导致血浆和组织池中单个游离氨基酸浓度发生显著变化。

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.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

摄入后，蛋白质在胃中被胃酸变性，同时被胃蛋白酶分解成更小的肽。这种酶在进食时由于胃酸增加而激活。然后，蛋白质和肽进入小肠，在那里肽键被多种酶水解。这些特定于肽键的酶来自胰腺，包括胰蛋白酶、胰凝乳蛋白酶、弹性蛋白酶和羧肽酶。产生的自由氨基酸和短肽混合物随后通过多种载体系统被转运到粘膜细胞中，这些载体系统专门用于特定的氨基酸和二肽和三肽，每种载体系统对肽底物的范围有限。吸收的肽在细胞内水解后，自由氨基酸通过粘膜细胞中的其他特定载体系统分泌到门静脉血液中，或者在细胞内进一步代谢。吸收的氨基酸进入肝脏，其中一部分被摄取和使用；其余的通过进入全身循环，被外周组织利用。/氨基酸/

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/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

蛋白质分泌到肠道中，即使在无蛋白饲料条件下也会继续，并且粪便中氮的丢失（即以细菌形式在粪便中丢失的氮）可能占到氮的强制性损失（即必需的氮损失）的25%。在这种情况下，作为蛋白水解酶的组成部分和脱落的粘膜细胞分泌到肠道的氨基酸是维持肠道细菌生物量的唯一氨基酸来源。... 完整氨基酸的其它丢失途径是通过尿液以及通过皮肤和毛发损失。与上述损失相比，这些损失较小，但尽管如此，在疾病状态下对需求估计的影响可能很大。/氨基酸/

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 percent 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/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S24/25
• 危险类别码：
  R40
• WGK Germany：
  3
• 海关编码：
  29224995
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  YV9361000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  本品应密封、置于阴凉干燥处并避免光照保存。

SDS

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模块 1. 化学品
1.1 产品标识符
: L-缬氨酸
产品名称
1.2 鉴别的其他方法
(S)-α-Aminoisovaleric acid
L-2-Amino-3-methylbutanoic acid
1.3 有关的确定了的物质或混合物的用途和建议不适合的用途
仅用于研发。不作为药品、家庭或其它用途。

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模块 2. 危险性概述
2.1 GHS-分类
非危险物质或混合物。
2.3 其它危害物 - 无

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模块 3. 成分/组成信息
3.1 物 质
: (S)-α-Aminoisovaleric acid
别名
L-2-Amino-3-methylbutanoic acid
: C5H11NO2
分子式
: 117.15 g/mol
分子量
无

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模块 4. 急救措施
4.1 必要的急救措施描述