Mevalonic acid
(Synonyms: 3,5-二羟基-3-甲基戊酸,MVA) 目录号 : GC30324
甲羟戊酸 (MVA) 是甲羟戊酸途径的前体物质，对细胞生长和增殖至关重要。
Cas No.:150-97-0
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 |
Simvastatin-induced loss of C2C12 myotube cell |
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Preparation Method |
0-110uM,72h |
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Reaction Conditions |
C2C12 myotubes were incubated with simvastatin for 72 h in the absence or presence of increasing amounts of mevalonic acid. Following incubation, cell viability was measured. Control incubations with DMSO or mevalonic acid, but no simvastatin. |
|
Applications |
C2C12 myotubes incubated with simvastatin manifested the expected decline in cell viability while myotubes incubated with simvastatin plus mevalonic acid showed no decline in cell viability at all mevalonic acid concentrations tested. Thus, it is concluded that mevalonic acid prevents manifestation of the deleterious effects of high-dose simvastatin treatment on C2C12 myotubes[1] . |
| Animal experiment [2]: | |
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Animal models |
SD rats |
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Preparation Method |
Mevalonic acid 150 mg·kg-1·d-1 was dissolved in 2 mL double-steamed water and gavaged for 1 week |
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Dosage form |
150 mg·kg-1·d-1 was dissolved in 2 mL double-steamed water |
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Applications |
Xuezhikang inhibited the Fas/FasL apoptosis pathway of myocardial cells in rats with ischemia/reperfusion, and then inhibited the apoptosis of cardiomyocytes, Mevalonic acid can attenuate the protective effect of Xuezhikang. |
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References: [1]. Moschetti A, Dagda RK, et,al. Coenzyme Q nanodisks counteract the effect of statins on C2C12 myotubes. Nanomedicine. 2021 Oct;37:102439. doi: 10.1016/j.nano.2021.102439. Epub 2021 Jul 10. PMID: 34256063; PMCID: PMC8464493. [2]. ZUO Hanheng, LI Yinping et,al. Effects of Xuezhikang on Cardiomyocyte Apoptosis. |
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Mevalonic acid is a precursor of cholesterol in the de novo biosynthetic pathway[1]. it is an important intermediate product of cholesterol and terpenoid synthesis, and plays an important role in regulating cell proliferation and collagen synthesis. Mevalonic acid stimulates HMGR expression and plays a key role in regulating cell growth[4].
C2C12 myotubes were incubated with simvastatin for 72 h in the absence or presence of increasing amounts of mevalonic acid. Following incubation, cell viability was measured . Control incubations with DMSO or mevalonic acid, but no simvastatin, had no effect on cell viability. C2C12 myotubes incubated with simvastatin manifested the expected decline in cell viability while myotubes incubated with simvastatin plus mevalonic acid showed no decline in cell viability at all mevalonic acid concentrations tested. Thus, it is concluded that mevalonic acid prevents manifestation of the deleterious effects of high-dose simvastatin treatment on C2C12 myotubes[2]. Mevalonic acid promotes tumor growth and, therefore, an increase in mevalonate synthesis in extrahepatic tissues following cholesterol-lowering therapy may explain the increased risk of cancer observed in some studies[5,6].Inhibition of the Mevalonic acid metabolic pathway in tumor cells elicits type 1 classical dendritic cells (cDC1) mediated tumor recognition and antigen cross-presentation for antitumor immunity. It demonstrates tumor Mevalonic acid metabolic blockade stimulates a cDC1 response through CLEC9A-mediated immune recognition of tumor cell cytoskeleton[3]. Mevalonic acid have become a focus area in research on the development of antitumor drugs [7].
In the mouse experiment, Xuezhikang inhibited the Fas/FasL apoptosis pathway of myocardial cells in rats with ischemia/reperfusion, and then inhibited the apoptosis of cardiomyocytes, Mevalonic acid can attenuate the protective effect of Xuezhikang[8].
References:
[1]: Naoumova RP, Marais AD, et,al. Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG-CoA reductase inhibitors in familial hypercholesterolaemia. Atherosclerosis. 1996 Jan 26;119(2):203-13. doi: 10.1016/0021-9150(95)05649-1. PMID: 8808497.
[2]: Moschetti A, Dagda RK, et,al. Coenzyme Q nanodisks counteract the effect of statins on C2C12 myotubes. Nanomedicine. 2021 Oct;37:102439. doi: 10.1016/j.nano.2021.102439. Epub 2021 Jul 10. PMID: 34256063; PMCID: PMC8464493.
[3]: Xu F, Wang Z, et,al. Mevalonate Blockade in Cancer Cells Triggers CLEC9A+ Dendritic Cell-Mediated Antitumor Immunity. Cancer Res. 2021 Sep 1;81(17):4514-4528. doi: 10.1158/0008-5472.CAN-20-3977. Epub 2021 Jul 15. PMID: 34266895.
[4]: Scoppola A, De Paolis P, et,al. Plasma mevalonate concentrations in uremic patients. Kidney Int. 1997 Mar;51(3):908-12. doi: 10.1038/ki.1997.128. PMID: 9067929.
[5]: Melhem MF, Gabriel HF, et,al. Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats. Br J Cancer. 1987 Jul;56(1):45-8. doi: 10.1038/bjc.1987.150. PMID: 3113472; PMCID: PMC2001672.
[6]: Rao KN, Melhem MF, et,al. Lipid composition and de novo cholesterogenesis in normal and neoplastic rat mammary tissues. J Natl Cancer Inst. 1988 Oct 5;80(15):1248-53. doi: 10.1093/jnci/80.15.1248. PMID: 3418731.
[7]: Duncan RE, El-Sohemy A, et,al. Mevalonate promotes the growth of tumors derived from human cancer cells in vivo and stimulates proliferation in vitro with enhanced cyclin-dependent kinase-2 activity. J Biol Chem. 2004 Aug 6;279(32):33079-84. doi: 10.1074/jbc.M400732200. Epub 2004 May 20. PMID: 15155733.
[8]: ZUO Hanheng, LI Yinping et,al. Effects of Xuezhikang on Cardiomyocyte Apoptosis.
甲羟戊酸是从头生物合成途径中胆固醇的前体[1]。它是胆固醇和萜类化合物合成的重要中间产物，对调节细胞增殖和胶原蛋白合成有重要作用。甲羟戊酸刺激HMGR表达并在调节细胞生长中起关键作用[4]。
C2C12 肌管在不存在或存在增加量的甲羟戊酸的情况下与辛伐他汀一起孵育 72 小时。孵育后，测量细胞活力。使用 DMSO 或甲羟戊酸（但不使用辛伐他汀）进行对照孵育对细胞活力没有影响。用辛伐他汀孵育的 C2C12 肌管表现出预期的细胞活力下降，而用辛伐他汀加甲羟戊酸孵育的肌管在所有测试的甲羟戊酸浓度下均未显示细胞活力下降。因此，可以得出结论，甲羟戊酸可防止大剂量辛伐他汀治疗对 C2C12 肌管的有害作用的表现[2]。甲羟戊酸促进肿瘤生长，因此，降低胆固醇治疗后肝外组织中甲羟戊酸合成的增加可能解释了一些研究中观察到的癌症风险增加的原因[5,6]。抑制甲羟戊酸肿瘤细胞中的酸代谢途径引发 1 型经典树突状细胞 (cDC1) 介导的肿瘤识别和抗原交叉呈递以实现抗肿瘤免疫。它表明肿瘤甲羟戊酸代谢阻断通过 CLEC9A 介导的肿瘤细胞骨架的免疫识别刺激 cDC1 反应[3]。甲羟戊酸已成为抗肿瘤药物开发研究的热点[7]。
小鼠实验中，血脂康通过抑制大鼠缺血/再灌注心肌细胞Fas/FasL凋亡通路，进而抑制心肌细胞凋亡，甲羟戊酸可减弱血脂康的保护作用[8]< /sup>.
| Cas No. | 150-97-0 | SDF | |
| 别名 | 3,5-二羟基-3-甲基戊酸,MVA | ||
| Canonical SMILES | O=C(O)CC(C)(O)CCO | ||
| 分子式 | C6H12O4 | 分子量 | 148.16 |
| 溶解度 | Soluble in DMSO | 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 | 6.7495 mL | 33.7473 mL | 67.4946 mL |
| 5 mM | 1.3499 mL | 6.7495 mL | 13.4989 mL |
| 10 mM | 0.6749 mL | 3.3747 mL | 6.7495 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。
Inhibition of cholesterol biosynthesis promotes the production of 1-octen-3-ol through mevalonic acid
1-Octen-3-ol makes an important contribution to meat flavor. The goal of this study was to identify the metabolic pathways of 1-octen-3-ol formation in meat. We found 218 metabolites associated with 1-octen-3-ol content in 20 samples of chicken meat, including mevalonic acid (positive correlation), corticosterone (negative correlation), and other lipids and lipid-like molecules. Among these 218 metabolites, 17 metabolites were differentially expressed in different 1-octen-3-ol content groups. Similarly, 37 genes were not only differentially expressed, but were significantly correlated with 1-octen-3-ol. The regulation of HSP90AA1, PTPN9, and other genes converted more mevalonic acid to 1-octen-3-ol. Meanwhile, mevalonic acid, a key material in the synthesis of cholesterol, caused a decrease in corticosterone content, affecting ZNF414 and KLF15 gene expression. These findings reveal the effect of cholesterol on 1-octen-3-ol content, as well as a positive regulation of mevalonic acid on the production of 1-octen-3-ol in chicken meat.
Plasma mevalonic acid exposure as a pharmacodynamic biomarker of fluvastatin/atorvastatin in healthy volunteers
Fluvastatin and atorvastatin are inhibitors of hydroxy-methylglutaryl-CoA (HMG-CoA) reductase, the enzyme that converts HMG-CoA to mevalonic acid (MVA). The present study reports for the first time the analysis of mevalonolactone (MVL) in plasma samples by UPLC-MS/MS as well as the use of MVA, analyzed as MVL, as a pharmacodynamics parameter of fluvastatin in multiple oral doses (20, 40 or 80 mg/day for 7 days) and atorvastatin in a single oral dose (20, 40 or 80 mg) in healthy female volunteers. this study presents the use of MVL exposure as a pharmacodynamics biomarker of fluvastatin in multiple oral doses (20, 40 or 80 mg/day for 7 days) or atorvastatin in a single oral dose (20, 40 or 80 mg) in healthy volunteers (n = 30). The administration of multiple doses of fluvastatin (n = 15) does not alter the values (geometric mean and 95 % CI) of AUC0-24 h of MVL [72.00 (57.49-90.18) vs 65.57 (51.73-83.12) ng?h/mL], but reduces AUC0-6 h [15.33 (11.85-19.83) vs 8.15 (6.18-10.75) ng?h/mL] by approximately 47 %, whereas single oral dose administration of atorvastatin (n = 15) reduces both AUC0-24 h [75.79 (65.10-88.24) vs 32.88 (27.05-39.96) ng?h/mL] and AUC0-6 h [17.07 (13.87-21.01) vs 7.01 (5.99-8.22) ng?h/mL] values by approximately 57 % and 59 %, respectively. In conclusion, the data show that the plasma exposure of MVL represents a reliable pharmacodynamic parameter for PK-PD (pharmacokinetic-pharmacodynamic) studies of fluvastatin in multiple doses and atorvastatin in a single dose.
Chemistry of mevalonic acid
The potential of the mevalonate pathway for enhanced isoprenoid production
The cytosol-localised mevalonic acid (MVA) pathway delivers the basic isoprene unit isopentenyl diphosphate (IPP). In higher plants, this central metabolic intermediate is also synthesised by the plastid-localised methylerythritol phosphate (MEP) pathway. Both MVA and MEP pathways conspire through exchange of intermediates and regulatory interactions. Products downstream of IPP such as phytosterols, carotenoids, vitamin E, artemisinin, tanshinone and paclitaxel demonstrate antioxidant, cholesterol-reducing, anti-ageing, anticancer, antimalarial, anti-inflammatory and antibacterial activities. Other isoprenoid precursors including isoprene, isoprenol, geraniol, farnesene and farnesol are economically valuable. An update on the MVA pathway and its interaction with the MEP pathway is presented, including the improvement in the production of phytosterols and other isoprenoid derivatives. Such attempts are for instance based on the bioengineering of microbes such as Escherichia coli and Saccharomyces cerevisiae, as well as plants. The function of relevant genes in the MVA pathway that can be utilised in metabolic engineering is reviewed and future perspectives are presented.