Methylarsonate(1-) | 51952-66-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: Methylarsonate(1-)
• 英文别名: hydroxy(methyl)arsinate
• CAS: 51952-66-0
• 化学式: CH4AsO3-
• 分子量: 138.962
• InChiKey: QYPPRTNMGCREIM-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.66
• 重原子数：
  5
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethanethiol anion 、 氢(+1)阳离子 、 Methylarsonate(1-) 生成 glutathione disulfide 、 水 、 甲烷亚胂酸
  参考文献：
  名称：

  欧米茄类谷胱甘肽转移酶的鉴定，表征和晶体结构。

  摘要：

  通过分析表达的序列标签数据库和序列比对，发现了一类新的谷胱甘肽转移酶。新型的谷胱甘肽S-转移酶（GST），名为Omega，存在于几种哺乳动物和秀丽隐杆线虫中。在人类中，GSTO 1-1在大多数组织中表达，并表现出谷胱甘肽毒素特有的谷胱甘肽依赖性硫醇转移酶和脱氢抗坏血酸还原酶活性。GSTO 1-1的结构已在2.0-A的分辨率下确定，并具有特征性的GST折叠（蛋白质数据库输入代码）。欧米茄（Omega）类GST表现出不寻常的N末端延伸，该末端邻接C末端形成一个新颖的结构单元。与其他哺乳动物GST不同，GSTO 1-1似乎具有一个活性位点的半胱氨酸，可以与谷胱甘肽形成二硫键。

  DOI：

  10.1074/jbc.m001706200
• 作为产物：
  描述：

  Dihydrogen arsenite 、 S-腺苷蛋氨酸 生成 氢(+1)阳离子 、 Methylarsonate(1-) 、 S-(5'-腺苷)-L-高半胱氨酸
  参考文献：
  名称：

  砷化合物的酶甲基化。七。单甲基ar酸（MMAIII）是兔肝和人肝细胞MMA甲基转移酶的底物。

  摘要：

  无机砷被一些（但不是全部）动物物种甲基化为二甲基砷酸（DMA）。已经提出了氧化态为+3的含砷的单甲基化合物作为中间体。使用来自兔肝的高度纯化的砷甲基转移酶和来自人类肝肝细胞的部分纯化的酶，Michaelis-Menten动力学表征了甲基characterized酸（MMAV）和甲基ar酸（MMAIII）作为底物的活性。兔肝酶对MMAIII的亲和力（Km = 0.92 x 10（-5）M）比MMAV（Km = 7.0 x 10（-5）M）大，因为Km越小，亲和力越大。此外，二硫醇，还原的硫辛酸或二硫苏糖醇在满足酶的硫醇需求方面似乎比GSH更具活性。尽管研究人员无法通过外科手术切除的人类肝脏检测到砷甲基转移酶，但现已确定其在常人肝细胞中的存在。使用来自昌人类肝细胞的MMAIII甲基转移酶，MMAIII的Km为3.04 x 10（-6），与兔肝酶的Km并无太大差异。

  DOI：

  10.1006/taap.1999.8687

文献信息

• Enzymic Methylation of Arsenic Compounds: Assay, Partial Purification, and Properties of Arsenite Methyltransferase and Monomethylarsonic Acid Methyltransferase of Rabbit Liver
  作者：Robert Zakharyan、Yuan Wu、Gregory M. Bogdan、H. Vasken Aposhian

  DOI：10.1021/tx00050a006

  日期：1995.12

  present time for these enzyme activities being on different protein molecules. Neither arsenate, selenate, selenite, or selenide are methylated by the purified enzyme preparations. Results from the use of crude extracts, often called cytosol, to study the properties of these methyltransferases dealing with arsenic species should be viewed with caution since such crude extracts contain inhibiting and

  已经开发出一种利用放射性S-腺苷甲硫氨酸（SAM）的快速，准确的体外测定方法，用于兔肝甲基转移酶对亚砷酸和单甲基ar酸酯（MMA）的甲基化。通过使用氯仿萃取，离子交换色谱，TLC或HPLC分离，鉴定和测量反应产物，已经验证了该测定法。已从兔肝中纯化了约2000倍的与该途径有关的酶，亚砷酸甲基转移酶和MMA甲基转移酶。凝胶电泳后，获得具有两个酶活性的单条带。纯化的亚砷酸甲基转移酶和单甲基ar磺酸甲基转移酶的最适pH分别为8.2和8.0。硫醇S-腺苷甲硫氨酸 对于部分纯化的亚砷酸盐甲基转移酶（催化一甲基ar磺酸盐的合成）而言，亚砷酸盐是必需的。催化单甲基ar酸酯甲基化为二甲基ar酸酯的另一种酶活性也需要SAM和巯基。尽管亚砷酸甲基转移酶和单甲基砷酸甲基转移酶具有不同的底物，最适pH和底物的饱和浓度，但仍无法确定两种活性是存在于一个蛋白质分子上还是存在于不同的蛋白质分子上。通过凝胶排阻色谱法测定
• A Novel S-Adenosyl-l-methionine:Arsenic(III) Methyltransferase from Rat Liver Cytosol
  作者：Shan Lin、Qing Shi、F. Brent Nix、Miroslav Styblo、Melinda A. Beck、Karen M. Herbin-Davis、Larry L. Hall、Josef B. Simeonsson、David J. Thomas

  DOI：10.1074/jbc.m110246200

  日期：2002.3

  S-Adenosyl-l-methionine (AdoMet):arsenic(III) methyltransferase, purified from liver cytosol of adult male Fischer 344 rats, catalyzes transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. The kinetics of production of methylated arsenicals in reaction mixtures containing enzyme, AdoMet, dithiothreitol, glutathione (GSH), and arsenite are consistent

  S-腺苷-1-蛋氨酸（AdoMet）：砷（III）甲基转移酶，是从成年雄性Fischer 344大鼠的肝细胞溶质中纯化的，催化甲基从AdoMet转移到三价砷中，产生甲基化和二甲基化的砷。在包含酶，AdoMet，二硫苏糖醇，谷胱甘肽（GSH）和亚砷酸盐的反应混合物中生成甲基化砷的动力学与以下方案一致：在方案中，由亚砷酸盐生产的单甲基化砷是第二个甲基化反应的底物，产生了二甲基化砷。该蛋白质的mRNA可以预测一个369个氨基酸的残基蛋白质（分子量41056），该蛋白质包含常见的甲基转移酶序列基序。其序列类似于在人和小鼠组织中表达的Cyt19，一种假定的甲基转移酶。逆转录聚合酶链反应可在大鼠组织和HepG2细胞（一种将亚砷酸和甲基砷酸甲基化的人类细胞系）中检测到S-腺苷-1-甲硫氨酸：砷（III）甲基转移酶mRNA。在UROtsa细胞中未检测到S-腺苷-1-甲硫氨酸：砷（III）甲基转移酶mRNA
• Human Monomethylarsonic Acid (MMA^V) Reductase Is a Member of the Glutathione-S-transferase Superfamily
  作者：Robert A. Zakharyan、Adriana Sampayo-Reyes、Sheila M. Healy、George Tsaprailis、Philip G. Board、Daniel C. Liebler、H. Vasken Aposhian

  DOI：10.1021/tx010052h

  日期：2001.8.1

  The drinking of water containing large amounts of inorganic arsenic is a worldwide major public health problem because of arsenic carcinogenicity. Yet an understanding of the specific mechanism(s) of inorganic arsenic toxicity has been elusive. We have now partially purified the rate-limiting enzyme of inorganic arsenic metabolism, human liver MMA(V) reductase, using ion exchange, molecular exclusion, and hydroxyapatite chromatography. When SDS-beta -mercaptoethanol -PAGE was performed on the most purified fraction, seven protein bands were obtained. Each band was excised from the gel, sequenced by LC-MS/MS and identified according to the SWISS-PROT and TrEMBL Protein Sequence databases. Human liver MMA(V) reductase is 100% identical, over 92% of sequence that we analyzed, with the recently discovered human glutathione-S-transferase Omega class hGSTO 1-1. Recombinant human GSTO1-1 had MMA(V) reductase activity with K-m and V-max values comparable to those of human liver MMA(V) reductase. The partially purified human liver MMAV reductase had glutathione S-transferase (GST) activity. MMA(V) reductase activity was competitively inhibited by the GST substrate, 1-chloro 2,4-dinitrobenzene and also by the GST inhibitor, deoxycholate. Western blot analysis of the most purified human liver MMA(V) reductase showed one band when probed with hGSTO1-1 antiserum. We propose that MMA(V) reductase and hGSTO 1-1 are identical proteins.
• Enzymatic Reduction of Arsenic Compounds in Mammalian Systems:  The Rate-Limiting Enzyme of Rabbit Liver Arsenic Biotransformation Is MMA^V Reductase
  作者：Robert A. Zakharyan、H. Vasken Aposhian

  DOI：10.1021/tx9901231

  日期：1999.12.1

  A unique enzyme, MMA(V) reductase, has been partially purified from rabbit liver by using DEAE-cellulose, carboxymethylcellulose, and red dye ligand chromatography. The enzyme is unique since it is the rate-limiting enzyme in the biotransformation of inorganic arsenite in rabbit liver. The K-m and V-max values were 2.16 x 10(-3) M and 10.3 mu mol h(-1) (mg of protein)(-1) When DMA(V) or arsenate was tested as a substrate, the K-m was 20.9 x 10(-9) or 109 x 10(-3) M, respectively. The enzyme has an absolute requirement for GSH. Other thiols such as DTT or L-cysteine were inactive alone. At a pH below the physiological pH, GSH carried out this reduction, but this GSH reduction in the absence of the enzyme had little if any value at pH 7.4. When the K-m values of rabbit liver arsenite methyltransferase (5.5 x 10(-6) M) and MMA(III) methyltransferase (9.2 x 10(-6)) were compared to that of MMA(V) reductase (2.16 x 10(-3) M), it can be concluded that MMAV reductase was the rate-limiting enzyme of inorganic arsenite biotransformation. MMAV reductase was also present in surgically removed human liver.
• Oxidative stress in<i>Caenorhabditis elegans</i>: protective effects of the Omega class glutathione transferase (<i>GSTO‐1</i>)
  作者：Cora Burmeister、Kai LÜersen、Alexander Heinick、Ayman Hussein、Marzena Domagalski、Rolf D. Walter、Eva Liebau

  DOI：10.1096/fj.06-7426com

  日期：2008.2

  To elucidate the function of Omega class glutathione transferases (GSTs) (EC 2.5.1.18) in multicellular organisms, the GSTO-1 from Caenorhabditis elegans (GSTO-1; C29E4.7) was investigated. Disc diffusion assays using Escherichia coli overexpressing GSTO-1 provided a test of resistance to long-term exposure under oxidative stress. After affinity purification, the recombinant GSTO-1 had minimal catalytic activity toward classic GST substrates but displayed significant thiol oxidoreductase and dehydroascorbate reductase activity. Microinjection of the GSTO-1-promoter green fluorescent protein construct and immunolocalization by electron microscopy localized the protein exclusively in the intestine of all postembryonic stages of C. elegans. Deletion analysis identified an similar to 300-nucleotide sequence upstream of the ATG start site necessary for GSTO-1 expression. Site-specific mutagenesis of a GATA transcription factor binding motif in the minimal promoter led to the loss of reporter expression. Similarly, RNA interference (RNAi) of Elt-2 indicated the involvement of this gut-specific transcription factor in GSTO-1 expression. Transcriptional upregulation under stress conditions of GSTO-1 was confirmed by analyzing promoter-reporter constructs in transgenic C. elegans strains. To investigate the function of GSTO-1 in vivo, transgenic animals overexpressing GSTO-1 were generated exhibiting an increased resistance to juglone-, paraquat-, and cumene hydroperoxide-induced oxidative stress. Specific silencing of the GSTO-1 by RNAi created worms with an increased sensitivity to several prooxidants, arsenite, and heat shock. We conclude that the stress-responsive GSTO-1 plays a key role in counteracting environmental stress.