β-mercaptopyruvate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: β-mercaptopyruvate
• 英文别名: 3-mercaptopyruvate；2-oxo-3-sulfanylpropanoate
• 化学式: C₃H₃O₃S
• 分子量: 119.121
• InChiKey: OJOLFAIGOXZBCI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  β-mercaptopyruvate 、 L-cysteine residue 生成 piruvate 、 S-sulfanyl-L-cysteine residue
  参考文献：
  名称：

  Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide

  摘要：

  H2S（硫化氢）最近被认为是一种信号分子和细胞保护剂。我们最近证明，3MST（3-巯基丙酮酸硫基转移酶）能从 3MP（3-巯基丙酮酸）产生 H2S。虽然 3MST 活性位点的中间过硫化物释放 H2S 需要还原性物质，但该物质尚未确定。本研究表明，Trx（硫氧还蛋白）和 DHLA（二氢硫辛酸）与 3MST 结合释放 H2S。其他还原性物质，如 NADPH、NADH、GSH、半胱氨酸和 CoA 对该反应没有任何影响。我们还发现，3MST 能从硫代硫酸盐中产生 H2S。本研究为 3MST 产生 H2S 的机制提供了新的见解。

  DOI：

  10.1042/bj20110841
• 作为产物：
  描述：

  2-氧代-戊二酸离子(2-) 、 L-半胱氨酸 生成 β-mercaptopyruvate 、 2-氨基戊二酸酯
  参考文献：
  名称：

  天冬氨酸转氨酶多肽链中必需酪氨酸残基的位置

  摘要：

  已知用四硝基甲烷处理的细胞质天冬氨酸转氨酶 (EC 1.6.1.1) 会部分丧失活性 [l]；在特殊条件下几乎完全失活伴随着酶中酪氨酸残基的选择性修饰 [2,3] 。在这里，我们提供的数据显示只有一个酪氨酸残基容易被硝化，并且它在多肽链中的位置是通过比较硝基酪氨酰肽的组成和来自天冬氨酸转氨酶的胰蛋白酶肽的已知序列来确定的。

  DOI：

  10.1016/0014-5793(72)80356-9

文献信息

• Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II
  作者：Qian Han、Tao Cai、Danilo A. Tagle、Howard Robinson、Jianyong Li

  DOI：10.1042/bsr20080085

  日期：2008.8.1

  KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to α-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested α-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with α-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15–33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.

  KAT（犬尿氨酸氨基转移酶）Ⅱ是大脑中催化犬尿氨酸转化为 KYNA（犬尿酸）的主要酶。KYNA 是唯一已知的 N-甲基-D-天冬氨酸受体内源性拮抗剂。这种酶还能催化氨基己二酸向α-氧代己二酸的转化，因此最初被命名为 AADAT（氨基己二酸氨基转移酶）。作为一种内毒素，氨基己二酸盐会影响谷氨酸能神经传递的各种因素，并杀死大脑中的原发性星形胶质细胞。文献中有许多关于这种酶的生物化学和功能特性的研究，但尚未对 KAT II 的底物概况和动力学特性进行系统评估。本研究探讨了人 KAT II/AADAT 的生化和结构特征。人 KAT II 的底物筛选显示，该酶具有非常广泛的底物特异性，能够催化 24 种测试氨基酸中 16 种氨基酸的转氨基反应，并能利用所有 16 种测试的 α-氧代酸作为氨基基团接受体。对人类 KAT II 的动力学分析表明了它对单个氨基基团供体和受体的催化效率，从而提供了有关其首选底物亲和性的信息。对人 KAT II 与 α-oxoglutaric acid 复合物的结构分析表明，其 N 端部分残基 15-33 发生了构象变化，能够适应不同大小的底物，这为其广泛的底物特异性提供了结构基础。
• Cysteine and keto acids modulate mosquito kynurenine aminotransferase catalyzed kynurenic acid production
  作者：Qian Han、Jianyong Li

  DOI：10.1016/j.febslet.2004.09.088

  日期：2004.11.19

  Kynurenine aminotransferase (KAT) catalyzes the formation of kynurenic acid (KYNA), the natural antagonist of ionotropic glutamate receptors. This study tests potential substrates and assesses the effects of amino acids and keto acids on the activity of mosquito KAT. Various keto acids, when simultaneously present in the same reaction mixture, display a combined effect on KAT catalyzed KYNA production. Moreover, methionine and glutamine show inhibitory effects on KAT activity, while cysteine functions as either an antagonist or an inhibitor depending on the concentration. Therefore, the overall level of keto acids and cysteine might modulate the KYNA synthesis. Results from this study will be useful in the study of KAT regulation in other animals.
• FIEDLER H.; WOOD J.L., J Biol Chem, 1956, 0021-9258, 387-97
  作者：FIEDLER H.、WOOD J.L.

  DOI：——

  日期：——
• Enzymic transfer of sulfur from mercaptopyruvate to sulfite or sulfinates
  作者：Bo Sörbo

  DOI：10.1016/0006-3002(57)90201-9

  日期：1957.1
• Post-translational Regulation of Mercaptopyruvate Sulfurtransferase via a Low Redox Potential Cysteine-sulfenate in the Maintenance of Redox Homeostasis
  作者：Noriyuki Nagahara、Akira Katayama

  DOI：10.1074/jbc.m505643200

  日期：2005.10

  3-Mercaptopyruvate sulfurtransferase (MST) (EC 2.8.1.2), a multifunctional enzyme, catalyzes a transsulfuration from mercaptopyruvate to pyruvate in the degradation process of cysteine. A stoichiometric concentration of hydrogen peroxide and of tetrathionate (S4O62-) inhibited rat MST (k(i) = 3.3 min(-1), K-i = 120.5 mu M and k(i) = 2.5 min(-1), K-i = 178.6 mu M, respectively). The activity was completely restored by dithiothreitol or thioredoxin with a reducing system containing thioredoxin reductase and NADPH, but glutathione did not restore the activity. On the other hand, an excess molar ratio dose of hydrogen peroxide inactivated MST. Oxidation with a stoichiometric concentration of hydrogen peroxide protected the enzyme against reaction by iodoacetate, which modifies a catalytic Cys(247), suggesting that Cys(247) is a target of the oxidants. A matrix-assisted laser desorption/ionization - time-of-flight mass spectrometric analysis revealed that hydrogen peroxide- and tetrathionate-inhibited MSTs were increased in molecular mass consistent with the addition of atomic oxygen and with a thiosulfate (S2O3-), respectively. Treatment with dithiothreitol restored modified MST to the original mass. These findings suggested that there was no nearby cysteine with which to form a disulfide, and mild oxidation of MST resulted in formation of a sulfenate (SO-) atCys(247), which exhibited exceptional stability and a lower redox potential than that of glutathione. Oxidative stress decreases MST activity so as to increase the amount of cysteine, a precursor of thioredoxin or glutathione, and furthermore, these cellular reductants restore the activity. Thus the redox state regulates MST activity at the enzymatic level, and on the other hand, MST controls redox to maintain cellular redox homeostasis.