4-Methyl-2-oxopentanoic acid
(Synonyms: 4-甲基-2-氧代戊酸,α-Ketoisocaproic acid) 目录号 : GC31307
4-Methyl-2-oxopentanoic acid是一种异常代谢物、神经毒素和代谢毒素。4-Methyl-2-oxopentanoic acid通过损害 mTOR 和自噬信号通路，增加内质网应激，促进前脂肪细胞脂质积累和胰岛素抵抗。
Cas No.:816-66-0
Sample solution is provided at 25 µL, 10mM.
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4-Methyl-2-oxopentanoic acid is an abnormal metabolite, a neurotoxin and a metabolic toxin. 4-Methyl-2-oxopentanoic acid increases endoplasmic reticulum stress, promotes lipid accumulation in preadipocytes and insulin resistance by impairing mTOR and autophagy signaling pathways[1] [2].
4-Methyl-2-oxopentanoic acid (0-300μM; 2d) treatment concentration-dependently increased lipid accumulation and the expression of lipogenic proteins, such as processed SREBP1 and SCD1, in 3T3-L1 preadipocytes[1]. 4-Methyl-2-oxopentanoic acid (1-10mM) reduced the HT-22 cells’ metabolic ability to reduce cytotoxicity and increased RS production in hippocampal neurons[2].
Mitochondrial complexes activities were reduced, and the formation of reactive species (RS) was increased in the hippocampus of rats after 4-Methyl-2-oxopentanoic acid (4mol/L, 2μL; ICV) administration[2].4-Methyl-2-oxopentanoic acid（10mmol/l; ICV） stimulated insulin secretion and elevated the NADPH/NADP+ ratio of islets preincubated in the absence of fuel[3].4-Methyl-2-oxopentanoic acid (400μmol/kg/h; carotid arch injection; single dose injection 60 min) increases porcine skeletal muscle protein synthesis and plasma leucine levels[4].
References:
[1].Park T J, Park S Y, Lee H J, et al. α-ketoisocaproic acid promotes ER stress through impairment of autophagy, thereby provoking lipid accumulation and insulin resistance in murine preadipocytes[J]. Biochemical and Biophysical Research Communications, 2022, 603: 109-115.
[2]. Farias H R, Gabriel J R, Cecconi M L, et al. The metabolic effect of α-ketoisocaproic acid: in vivo and in vitro studies[J]. Metabolic Brain Disease, 2021, 36: 185-192.
[3]. Panten U, Rustenbeck I. Fuel-induced amplification of insulin secretion in mouse pancreatic islets exposed to a high sulfonylurea concentration: role of the NADPH/NADP+ ratio[J]. Diabetologia, 2008, 51: 101-109.
[4]. Escobar J, Frank J W, Suryawan A, et al. Leucine and α-ketoisocaproic acid, but not norleucine, stimulate skeletal muscle protein synthesis in neonatal pigs[J]. The Journal of nutrition, 2010, 140(8): 1418-1424.
4-Methyl-2-oxopentanoic acid是一种异常代谢物、神经毒素和代谢毒素。4-Methyl-2-oxopentanoic acid通过损害 mTOR 和自噬信号通路，增加内质网应激，促进前脂肪细胞脂质积累和胰岛素抵抗[1][2]。
4-Methyl-2-oxopentanoic acid (0-300μM; 2d) 处理3T3-L1前脂肪细胞，以浓度依赖性增加了细胞中的脂质积累和脂肪生成蛋白（如加工的SREBP1和SCD1）表达[1]。4-Methyl-2-oxopentanoic acid（1-10mM）降低了HT-22细胞的代谢能力，从而减少了细胞毒性，并增加了海马神经元中活性物质的产生[2]。
给大鼠注射4-Methyl-2-oxopentanoic acid（4mol/L，2μL；ICV）后，大鼠海马线粒体复合物活性降低，活性物质（RS）的形成增加[2]。4-Methyl-2-oxopentanoic acid（10mmol/l；ICV） 刺激胰岛素分泌，并提高无燃料预孵育胰岛的 NADPH/NADP+ 比率[3]。4-Methyl-2-oxopentanoic acid（400μmol/kg/h；颈动脉弓注射；单剂量注射 60 分钟）可增加猪骨骼肌蛋白质合成和血浆亮氨酸水平[4]。
| Cell experiment [1]: | |
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Cell lines |
Mouse preadipocyte 3T3-L1 cells |
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Preparation Method |
Mouse preadipocyte 3T3-L1 cells were treated with 0–300μM 4-Methyl-2-oxopentanoic acid for 2 days. |
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Reaction Conditions |
0-300μM; 2d |
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Applications |
4-Methyl-2-oxopentanoic acid treatment concentration-dependently increased lipid accumulation and the expression of lipogenic proteins, such as processed SREBP1 and SCD1, in 3T3-L1 preadipocytes. |
| Animal experiment [2]: | |
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Animal models |
KIC exposure modle |
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Preparation Method |
30-day-old male Wistar rats were anesthetized and placed in a stereotaxic apparatus, and two small holes were drilled in the skull (bilaterally) to inject 2µL of 4-Methyl-2-oxopentanoic acid or aCSF (control). The solution was slowly injected into the lateral ventricle over 4 minutes. The needle was left in place for 1 minute and then gently withdrawn. 4-Methyl-2-oxopentanoic acid solution (4µmol, pH 7.4) was dissolved in freshly prepared artificial cerebrospinal fluid (aCSF) (147mM NaCl; 2.9mM KCl; 1.6mM MgCl2; 1.7mM CaCl2 and 2.2mM glucose). One hour after administration, the animals were killed by decapitation, and the hippocampus was dissected. |
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Dosage form |
4mol/L, 2μL; ICV |
|
Applications |
Mitochondrial complexes activities were reduced, and the formation of RS was increased in the hippocampus of rats after 4-Methyl-2-oxopentanoic acid administration. |
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References: |
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| Cas No. | 816-66-0 | SDF | |
| 别名 | 4-甲基-2-氧代戊酸,α-Ketoisocaproic acid | ||
| Canonical SMILES | CC(C)CC(C(O)=O)=O | ||
| 分子式 | C6H10O3 | 分子量 | 130.14 |
| 溶解度 | DMSO: ≥ 100 mg/mL (768.40 mM); Water: 100 mg/mL (768.40 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 7.684 mL | 38.4202 mL | 76.8403 mL |
| 5 mM | 1.5368 mL | 7.684 mL | 15.3681 mL |
| 10 mM | 0.7684 mL | 3.842 mL | 7.684 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet