S-Adenosylhomocysteine
(Synonyms: S-(5'-腺苷)-L-高半胱氨酸,SAH (S-Adenosylhomocysteine); AdoHcy) 目录号 : GC10396
Amino acid derivative
Cas No.:979-92-0
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
| Kinase experiment [1]: | |
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Preparation Method |
The reaction was run in 8 complete rows (half plate) with or without a known inhibitor. S-adenosylhomocysteine was used as an inhibitor for METTL3-14. |
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Reaction Conditions |
0-100?M S-adenosylhomocysteine |
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Applications |
S-adenosylhomocysteine showed strong inhibitory effects on METTL3-14 activity with an IC50 value of 0.9±0.1?M. |
| Cell experiment [2]: | |
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Cell lines |
WY2 and WY35(cys4? strains) |
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Preparation Method |
Saturated 2-day-old cultures of the WY2 and WY35 were diluted to an OD600 of approximately 0.05. S-adenosylhomocysteine was added at concentration at 25, 50, 100, 600?M. Growth was monitored by observing OD600 at specific time points during the course of 24h |
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Reaction Conditions |
25, 50, 100, 600?M S-adenosylhomocysteine, 24h |
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Applications |
As little as 25?M S-adenosylhomocysteine showed measurable growth inhibition with the doubling time increasing about 15% from 222 to 256min. Exposure to 600?M S-adenosylhomocysteine increased the doubling time 206%, from 222 to 680min. |
| Animal experiment [3]: | |
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Animal models |
zebrafishes (F0) carrying the ahcyl1-KO allele |
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Preparation Method |
The identified chimeras were raised and crossed to wild-type zebrafish. The fertilized eggs were collected and injected with 0 or 5mM S-adenosylhomocysteine and RFP-LC3 mRNA at one-cell stage. For the injection of 5mM S-adenosylhomocysteine, the final concentration of injected S-adenosylhomocysteine was about 5?M. 26h after fertilization, the embryos were fixed by 8% paraformaldehyde with DAPI overnight. |
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Dosage form |
0 or 5mM S-adenosylhomocysteine, the final concentration of injected S-adenosylhomocysteine was about 5?M, embryo injection, 26h |
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Applications |
Less LC3 puncta was observed when injected with S-adenosylhomocysteine. When one allele of ahcyl1 was knocked out, a mild increase of LC3 puncta was observed and the decrease of LC3 puncta by S-adenosylhomocysteine was significantly weakened. These results demonstrated that AHCYL1 senses the increased S-adenosylhomocysteine to inhibit autophagy in zebrafish. |
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References: [1]. Li F, Kennedy S, et al. A Radioactivity-Based Assay for Screening Human m6A-RNA Methyltransferase, METTL3-METTL14 Complex, and Demethylase ALKBH5. J Biomol Screen. 2016;21(3):290-297. [2]. Christopher SA, Melnyk S, et al. S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta-synthase. Mol Genet Metab. 2002;75(4):335-343. [3]. Huang W, Li N, et al. AHCYL1 senses SAH to inhibit autophagy through interaction with PIK3C3 in an MTORC1-independent manner. Autophagy. 2022;18(2):309-319. |
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S-adenosylhomocysteine (SAH), an amino acid derivative, is a key intermediate metabolite in
methionine metabolism[1]. It is an intermediate in the synthesis of cysteine and adenosine[2]. S-adenosylhomocysteine inhibited METTL3-14 activity with an IC50 value of 0.9 ± 0.1 µM[3].
S-adenosylhomocysteine(25 µM) inhibited the growth of CBS deficient yeast, but had no effect on wild-type yeast. Growth inhibition by S-adenosylhomocysteine in CBS deficient yeast can be totally reversed by addition of SAM to the media[4]. High S-adenosylhomocysteine levels inhibited NFκB-mediated gene expression and sensitized primary hepatocytes and HepG2 cells to the cytotoxic effects of TNF[5]. Increased adipose S-adenosylhomocysteine levels generate methylation defects that promote lipolysis. Alcohol-induced increases in hepatocellular S-adenosylhomocysteine and the resultant lowering of SAM/SAH ratio lead to the pathogenesis and progression of ALD[6].
S-adenosylhomocysteine enhances the interaction between AHCYL1 and PIK3C3. When cells are in the presence of S-adenosylhomocysteine, the enhanced interaction suppresses the production of PtdIns3P, which blocks the autophagy initiation. When in the absence of S-adenosylhomocysteine, the decreased interaction releases PIK3C3 to produce PtdIns3P, eventually promotes autophagy[1]. CKD was associated with a low SAM level and SAM/SAH ratio in urine. The use of the SAM level or the SAM/SAH ratio in urine could be considered as a promising, noninvasive indicator of renal dysfunction[7].
References:
[1] Huang W, Li N, et al. AHCYL1 senses SAH to inhibit autophagy through interaction with PIK3C3 in an MTORC1-independent manner. Autophagy. 2022;18(2):309-319.
[2] DE LA HABA G, et al. The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine. J Biol Chem. 1959;234(3):603-608.
[3] Li F, Kennedy S, et al. A Radioactivity-Based Assay for Screening Human m6A-RNA Methyltransferase, METTL3-METTL14 Complex, and Demethylase ALKBH5. J Biomol Screen. 2016;21(3):290-297.
[4] Christopher SA, Melnyk S, et al. S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta-synthase. Mol Genet Metab. 2002;75(4):335-343.
[5] Watson WH, Burke TJ, et al. S-adenosylhomocysteine inhibits NF-κB-mediated gene expression in hepatocytes and confers sensitivity to TNF cytotoxicity. Alcohol Clin Exp Res. 2014;38(4):889-896.
[6] Arumugam MK, Chava S, et al. Elevated S-adenosylhomocysteine induces adipocyte dysfunction to promote alcohol-associated liver steatosis. Sci Rep. 2021;11(1):14693. Published 2021 Jul 19.
[7] Kruglova MP, Grachev SV, et al. Low S-adenosylmethionine/ S-adenosylhomocysteine Ratio in Urine is Associated with Chronic Kidney Disease. Lab Med. 2020;51(1):80-85.
S-腺苷同型半胱氨酸 (SAH) 是一种氨基酸衍生物，是
蛋氨酸代谢[1] 中的关键中间代谢产物。它是半胱氨酸和腺苷合成的中间体[2]。 S-腺苷同型半胱氨酸抑制 METTL3-14 活性，IC50 值为 0.9 ±； 0.1 µM[3].
S-腺苷同型半胱氨酸(25 µM)抑制CBS缺陷型酵母的生长，但对野生型酵母没有影响。在培养基中添加 SAM 可以完全逆转 S-腺苷高半胱氨酸对 CBS 缺陷酵母的生长抑制作用[4]。高 S-腺苷同型半胱氨酸水平抑制 NFκB 介导的基因表达，并使原代肝细胞和 HepG2 细胞对 TNF 的细胞毒性作用敏感[5]。增加的脂肪 S-腺苷同型半胱氨酸水平会产生促进脂肪分解的甲基化缺陷。酒精诱导的肝细胞 S-腺苷同型半胱氨酸增加以及由此导致的 SAM/SAH 比值降低导致 ALD 的发病机制和进展[6]。
S-腺苷同型半胱氨酸增强相互作用在 AHCYL1 和 PIK3C3 之间。当细胞存在 S-腺苷同型半胱氨酸时，增强的相互作用会抑制 PtdIns3P 的产生，从而阻止自噬启动。当 S-腺苷同型半胱氨酸不存在时，减少的相互作用释放 PIK3C3 产生 PtdIns3P，最终促进自噬[1]。 CKD 与尿液中的低 SAM 水平和 SAM/SAH 比值相关。尿液中 SAM 水平或 SAM/SAH 比值可被视为肾功能不全的有前途的非侵入性指标[7]。
| Cas No. | 979-92-0 | SDF | |
| 别名 | S-(5'-腺苷)-L-高半胱氨酸,SAH (S-Adenosylhomocysteine); AdoHcy | ||
| 化学名 | (S)-2-amino-4-((((2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)thio)butanoic acid | ||
| Canonical SMILES | O[C@@H]1[C@@H]([C@H](O[C@H]1N2C3=C(N=C2)C(N)=NC=N3)CSCC[C@@H](C(O)=O)N)O | ||
| 分子式 | C14H20N6O5S | 分子量 | 384.41 |
| 溶解度 | ≥ 8.56 mg/mL in DMSO with ultrasonic and warming, ≥ 45.3 mg/mL in Water with gentle warming | 储存条件 | Store at -20°C, protect from light |
| 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 | 2.6014 mL | 13.0069 mL | 26.0139 mL |
| 5 mM | 0.5203 mL | 2.6014 mL | 5.2028 mL |
| 10 mM | 0.2601 mL | 1.3007 mL | 2.6014 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 S-adenosylhomocysteine hydrolase induces endothelial senescence via hTERT downregulation
Background and aims: It has been established that endothelial senescence plays a critical role in the development of atherosclerosis. Elevated S-adenosylhomocysteine (SAH) level induced by inhibition of S-adenosylhomocysteine hydrolase (SAHH) is one of the risk factors of atherosclerosis; however, the interplay between endothelial senescence and inhibition of SAHH is largely unknown. Methods: Human umbilical vein endothelial cells (HUVECs) after serial passage were used. SAHH-specific inhibitor adenosine dialdehyde (ADA) and SAHH siRNA treated HUVECs and SAHH+/-mice were used to investigate the effect of SAHH inhibition on endothelial senescence. Results: HUVECs exhibited distinct senescence morphology as HUVECs were passaged, together with a decrease in intracellular SAHH expression and an increase in intracellular SAH levels. SAHH inhibition by ADA or SAHH siRNA elevated SA β-gal activity, arrested proliferation, and increased the expression of p16, p21 and p53 in HUVECs and the aortas of mice. In addition, decreased expression of hTERT and reduced occupancy of H3K4me3 over the hTERT promoter region were observed following SAHH inhibition treatment. To further verify the role of hTERT in the endothelial senescence induced by SAHH inhibition, hTERT was overexpressed with a plasmid vector under CMV promoter. hTERT overexpression rescued the senescence phenotypes in endothelial cells induced by SAHH inhibition. Conclusions: SAHH inhibition induces endothelial senescence via downregulation of hTERT expression, which is associated with attenuated histone methylation over the hTERT promoter region.
Insufficient S-adenosylhomocysteine hydrolase compromises the beneficial effect of diabetic BMSCs on diabetic cardiomyopathy
Background: Autologous stem cell therapy is a promising strategy for cardiovascular diseases including diabetic cardiomyopathy (DCM), but conclusions from clinical trials were compromised. We assumed that diabetes might induce the dysfunction of stem cells and thus limit its therapeutic effect. This study aimed to compare the effect of diabetes and nondiabetes-derived bone marrow mesenchymal stem cells (BMSCs) transplantation on DCM and explored the potential mechanism.
Methods: Rats with diabetes were induced using high-fat diets and streptozotocin (STZ) injection. BMSCs harvested from diabetic and nondiabetic rats were infused into DCM rats, and the effects on the heart were identified by echocardiography and histopathology. The inhibition or overexpression of SAHH in nondiabetic and diabetic BMSCs was used to confirm its key role in stem cell activity and cardiac therapy.
Results: Compared with normal BMSCs, the therapeutic effects of diabetic rat-derived stem cells on improving cardiac function and adverse remodeling were significantly attenuated. In vitro, diabetic BMSCs had lower cell viability and paracrine function than nondiabetic BMSCs. It was further found that diabetic BMSCs had obvious mitochondrial oxidative stress damage and S-adenosylhomocysteine (SAH) accumulation due to S-adenosylhomocysteine hydrolase (SAHH) deficiency. SAHH inhibition by adenosine dialdehyde (ADA) or shSAHH plasmid in normal BMSCs significantly reduced the favorable effects on endothelial cell proliferation and tube-forming capacity. In contrast, SAHH overexpression in diabetic BMSCs significantly improved cellular activity and paracrine function. Transplantation of BMSCs with SAHH overexpression improved cardiac adverse remodeling and angiogenesis. Activation of the Nrf2 signaling pathway may be one of the key mechanisms of SAHH-mediated improvement of stem cell viability and cardiac repair.
Conclusions: Diabetes leads to compromised bioactivity and repair capacity of BMSCs. Our study suggests that SAHH activation may improve the cardioprotective effect of autologous transplantation of diabetes-derived BMSCs on patients with DCM. Diabetes induced the inhibition of S-adenosylhomocysteine (SAH) expression and aging phenotype in BMSCs and thus decreased the cell viability and paracrine function. Compared with normal BMSCs, the therapeutic effects of diabetic rat-derived BMSCs on improving cardiac function and adverse remodeling were significantly attenuated. SAHH overexpression in diabetic BMSCs significantly rescued cellular function partly via activating Nrf2/HO-1 signal. Transplantation of diabetic BMSCs with SAHH overexpression improved angiogenesis and cardiac adverse remodeling in rats.
S-adenosylhomocysteine induces cellular senescence in rat aorta vascular smooth muscle cells via NF-κB-SASP pathway
Vascular aging plays an important role in the development and progression of atherosclerosis (AS) , and one-carbon metabolism dysfunction will lead to Vascular Smooth Muscle Cells (VSMCs) senescence, which contributes to vascular senescence. However, the mechanisms underlying the role of VSMCs senescence in AS remain unclear. This study aimed to evaluate S-adenosyl-homocysteine (SAH) as a one-carbon metabolite that affects VSMCs senescence. We treated Rat Aorta Smooth Muscle Cells (RASMCs) with S-adenosylhomocysteine Hydrolase (SAHH) inhibitor, adenosine-2,3-dialdehyde (ADA) and SAHH siRNA to examine the effect of elevated SAH levels on RASMCs phenotypes. SAHH inhibition induced RASMCs senescence, as demonstrated by the manifestation of senescence-associated secretory phenotype in cells and induction of senescence in pre-senescent RASMCs. Furthermore, we found that SAHH inhibition induced CpG island demethylation in the promoter of NF-κB, a molecule that drives the pro-inflammatory response of the cells manifesting the senescence-associated secretory phenotype (SASP). Overall, these findings indicate that the elevated intracellular SAH levels could be targeted to ameliorate vascular aging.
S-Adenosylhomocysteine hydrolase as a target for intracellular adenosine action
S-Adenosylhomocysteine hydrolase (AdoHcyase) controls intracellular levels of S-adenosylhomocysteine (AdoHcy). AdoHcy is a potent product inhibitor of some S-adenosylmethionine-dependent methyltransferases. Pharmacological modulation of AdoHcyase to indirectly inhibit methyltransferases can be guided by the fact that adenosine binds with high affinity to AdoHcyase and inhibits enzyme activity. cAMP can compete with adenosine and can counteract the adenosine-induced inhibition of AdoHcyase. Thus, the ratio between adenosine and cAMP, which can vary under different physiological conditions, might result in changes in, for example, DNA promoter methylation and therefore transcription.
S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine?
It is widely accepted that elevated plasma total homocysteine is an independent risk factor for vascular disease. The relation is believed to be causal, but there is no generally accepted mechanism for the pathophysiology involved. The metabolic precursor of homocysteine in all tissues is S-adenosylhomocysteine (AdoHcy). AdoHcy is present in normal human plasma at concentrations approximately 1-500th of those of homocysteine, a fact that presents difficulties in measurement. The requirement for specialized equipment, complicated time-consuming methodology, or both is a reason that measurement of plasma AdoHcy has not generally been carried out in large studies. A recently published rapid immunoassay for AdoHcy in human plasma should make measurement of this important metabolite available for general use. Advantages of the measurement of plasma AdoHcy include 1) a smaller overlap of values between control subjects and patients, and thus the possibility of observing significant differences in fewer samples, 2) an accepted mechanism of metabolic activity as an inhibitor of all S-adenosylmethionine-mediated methyltransferases, and 3) evidence (from recent studies) that a higher plasma concentration of AdoHcy is a more sensitive indicator of vascular disease than is a higher plasma concentration of homocysteine.