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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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| 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 The needle was left in place for 1 minute and then gently withdrawn. 4-Methyl-2-oxopentanoic acid solution (4µmol, pH 7.4) was dissolved in freshly prepared artificial cerebrospinal fluid (aCSF) (147mM NaCl; 2.9mM KCl; 1.6mM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 |
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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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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]。
| 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。
Regulatory effects of fatty acids on decarboxylation of leucine and 4-methyl-2-oxopentanoate in the perfused rat heart
The regulatory effects of fatty acids on the oxidative decarboxylation of leucine and 4-methyl-2-oxopentanoate were investigated in the isolated rat heart. Infusion of the long-chain fatty acid palmitate resulted in both an inactivation of the branched-chain 2-oxo acid dehydrogenase and an inhibition of the measured metabolic flux through this enzyme complex. Pyruvate addition also caused both an inactivation and an inhibition of the flux through the complex. On the other hand, the medium-chain fatty acid octanoate caused an activation of and a stimulation of flux through the branched-chain 2-oxo acid dehydrogenase when the perfusion conditions before octanoate addition maintained the enzyme complex in its inactive state. When the enzyme complex was activated before octanoate infusion, this fatty acid caused a significant inhibition of the flux through the branched-chain 2-oxo acid dehydrogenase reaction. Inclusion of glucose in the perfusion medium prevented the octanoate-mediated activation of the branched-chain 2-oxo acid dehydrogenase.
Assessment of the flux of mitochondrial acetyl-CoA in liver and kidney by using the differential production of 14CO2 from tracers of (1-14C)- and (2-14C)-labelled 4-methyl-2-oxovalerate
A procedure is described to convert rates of (14)CO(2) production into rates of mitochondrial acetyl-CoA production from a (14)C-labelled substrate. The principle is illustrated in perfused rat liver and kidney by the differential yield of (14)CO(2) from 4-methyl-2-oxo[1-(14)C]valerate and 4-methyl-2-oxo[2-(14)C]valerate.
Actions of GIP
Two structurally similar peptides were isolated from a preparation of GIP using an HPLC system. The major peptide corresponds to GIP1-42 and the minor has the sequence GIP3-42. GIP1-42 has both insulinotropic and somatostatinotropic activities, whereas GIP3-42 has only insignificant activity. GIP was also shown to potentiate insulin release initiated by D-glyceraldehyde, L-leucine/L-glutamine and 2-keto-isocaproic acid. No potentiation was observed with 2-ketocaproate. The 4 substrates studied are all metabolized but via different mechanisms.
Engineering of L-amino acid deaminases for the production of α-keto acids from L-amino acids
α-keto acids are organic compounds that contain an acid group and a ketone group. L-amino acid deaminases are enzymes that catalyze the oxidative deamination of amino acids for the formation of their corresponding α-keto acids and ammonia. α-keto acids are synthesized industrially via chemical processes that are costly and use harsh chemicals. The use of the directed evolution technique, followed by the screening and selection of desirable variants, to evolve enzymes has proven to be an effective way to engineer enzymes with improved performance. This review presents recent studies in which the directed evolution technique was used to evolve enzymes, with an emphasis on L-amino acid deaminases for the whole-cell biocatalysts production of α-keto acids from their corresponding L-amino acids. We discuss and highlight recent cases where the engineered L-amino acid deaminases resulted in an improved production yield of phenylpyruvic acid, α-ketoisocaproate, α-ketoisovaleric acid, α-ketoglutaric acid, α-keto-γ-methylthiobutyric acid, and pyruvate.
Oxidation of 2-oxoisocaproate and 2-oxoisovalerate by the perfused rat heart. Interactions with fatty acid oxidation
The interactions between fatty acid oxidation and the oxidation of the 2-oxo acids of the branched chain amino acids were studied in the isolated Langendorff-perfused heart. 2-Oxoisocaproate inhibited the oxidation of oleate, but 2-oxoisovalerate and 2-oxo-3-methylvalerate did not. This difference was not attributable to the magnitude of the flux through the branched chain 2-oxo acid dehydrogenase, which was slightly higher with 2-oxoisovalerate than with 2-oxoisocaproate. Oxidation of 2-oxoisocaproate in the perfused heart was virtually complete, since more than 80% of the isovaleryl-CoA formed from 2-oxo[1-14C]isocaproate was further metabolized to CO2, as determined by comparing 14CO2 production from 2-oxo[14C(U)]isocaproate with that from the 1-14C-labelled compound. Only twice as much 14CO2 was produced from 2-oxo[14C(U)]isovalerate as from the 1-14C-labelled compound, indicating incomplete oxidation. This was confirmed by the accumulation in the perfusion medium of substantial quantities of labelled 3-hydroxyisobutyrate (an intermediate in the pathway of valine catabolism), when hearts were perfused with 2-oxo[14C(U)]isovalerate. The failure of 2-oxoisovalerate to inhibit fatty acid oxidation, then, can be attributed to the fact that its partial metabolism in the heart produces little ATP. We have previously shown that 3-hydroxyisobutyrate is a good gluconeogenic substrate in liver and kidney, and postulate that 3-hydroxyisobutyrate serves as an interorgan metabolite such that valine can serve as a glucogenic amino acid, even when its catabolism proceeds beyond the irreversible 2-oxo acid dehydrogenase in muscle.