(2S)-2-isopropylmalate(2-)

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2S)-2-isopropylmalate(2-)
• 英文别名: (2S)-2-hydroxy-2-propan-2-ylbutanedioate
• 化学式: C7H10O5-2
• 分子量: 174.15
• InChiKey: BITYXLXUCSKTJS-ZETCQYMHSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2R,3S)-3-Isopropylmalate 生成 (2S)-2-isopropylmalate(2-)
  参考文献：
  名称：

  詹氏甲烷球菌中丙酮酸生成2-氧代丁酸酯的途径的酶学和演化。

  摘要：

  古代甲烷甲烷球菌使用三种不同的2-含氧酸延长途径，这些途径延长了亮氨酸，异亮氨酸和辅酶B生物合成中前体的链长。在这些途径的每一种中，乌头酸酶型水解酶催化羟酸异构化反应。詹氏甲烷球菌的基因组序列编码形成水解酶的每个大亚基和小亚基的两个同源物，但是这些基因不是共转录的。这些基因彼此之间比以前表征的苹果酸异丙酯异构酶或高纯硝酸酶基因更相似。为了鉴定这些同源物的功能，亚单位的四种组合在大肠杆菌中异源表达，纯化并重建以产生全酶的铁硫中心。只有MJ0499和MJ1277蛋白的组合才能催化苹果酸异丙酯和柠檬酸酯的异构化反应。该对还使用柠檬酸柠檬酸酯和马来酸酯催化水合半反应。另一种广泛特异性的酶，苹果酸异丙酯脱氢酶（MJ0720）催化β-异丙基苹果酸，β-甲基苹果酸和d-苹果酸的氧化脱羧。结合这些结果，系统发育分析表明，丙酮酸通向2-氧代丁酸的途径（异亮氨酸生物合成中苏氨酸脱水酶的替代物）在细菌和古细菌中

  DOI：

  10.1128/jb.00166-07

文献信息

• Isoleucine Biosynthesis in <i>Leptospira interrogans</i> Serotype lai Strain 56601 Proceeds via a Threonine-Independent Pathway
  作者：Hai Xu、Yuzhen Zhang、Xiaokui Guo、Shuangxi Ren、Andreas A. Staempfli、Juishen Chiao、Weihong Jiang、Guoping Zhao

  DOI：10.1128/jb.186.16.5400-5409.2004

  日期：2004.8.15

  Three leuA -like protein-coding sequences were identified in Leptospira interrogans . One of these, the cimA gene, was shown to encode citramalate synthase (EC 4.1.3.-). The other two encoded α-isopropylmalate synthase (EC 4.1.3.12). Expressed in Escherichia coli , the citramalate synthase was purified and characterized. Although its activity was relatively low, it was strictly specific for pyruvate as the keto acid substrate. Unlike the citramalate synthase of the thermophile Methanococcus jannaschii , the L. interrogans enzyme is temperature sensitive but exhibits a much lower K _m (0.04 mM) for pyruvate. The reaction product was characterized as ( R )-citramalate, and the proposed β-methyl- d -malate pathway was further confirmed by demonstrating that citraconate was the substrate for the following reaction. This alternative pathway for isoleucine biosynthesis from pyruvate was analyzed both in vitro by assays of leptospiral isopropylmalate isomerase (EC 4.2.1.33) and β-isopropylmalate dehydrogenase (EC 1.1.1.85) in E. coli extracts bearing the corresponding clones and in vivo by complementation of E. coli ilvA , leuC / D , and leuB mutants. Thus, the existence of a leucine-like pathway for isoleucine biosynthesis in L. interrogans under physiological conditions was unequivocally proven. Significant variations in either the enzymatic activities or mRNA levels of the cimA and leuA genes were detected in L. interrogans grown on minimal medium supplemented with different levels of the corresponding amino acids or in cells grown on serum-containing rich medium. The similarity of this metabolic pathway in leptospires and archaea is consistent with the evolutionarily primitive status of the eubacterial spirochetes.

  摘要 三 leuA -蛋白编码序列。 钩端螺旋体 .其中一个 cimA 基因编码柠檬醛酸合成酶（EC 4.1.3.-）。另外两个基因编码α-异丙基丙二酸合成酶（EC 4.1.3.12）。在 大肠杆菌 纯化并鉴定了柠檬丙二酸合成酶。虽然其活性相对较低，但它对酮酸底物丙酮酸具有严格的特异性。与嗜热菌的柠檬醛酸合成酶不同的是 不同。 不同的是 L. interrogans 酶对温度敏感，但它对酮酸底物丙酮酸的特异性要低得多。 K m (0.04 mM）。反应产物的特征为 R )-柠檬醛酸，以及拟议的 β-甲基-(R) d 通过证明柠檬酸盐是接下来反应的底物，进一步证实了所提出的 β-甲基-d-丙二酸盐途径。通过检测大肠杆菌中的钩端螺旋异丙基丙二酸异构酶（EC 4.2.1.33）和 β-异丙基丙二酸脱氢酶（EC 1.1.1.85），分析了丙酮酸异亮氨酸的体外生物合成途径。 大肠杆菌 大肠杆菌ilvA 的互补作用，在含有相应克隆的大肠杆菌提取物和体内 大肠杆菌 ilvA , leuC / D 和 突变体 突变体。因此，异亮氨酸生物合成的亮氨酸样途径存在于 L. interrogans 在生理条件下异亮氨酸生物合成途径的存在得到了明确的证明。cimA 突变体的酶活性或 mRNA 水平的显著变化 cimA 和 leuA 基因在 L. interrogans 细胞中检测到了 cimA 和 leuA 基因。这种代谢途径在钩端螺旋体和古细菌中的相似性与真细菌螺旋体在进化过程中的原始地位是一致的。
• The Absolute Configuration of α-carboxyisocaproic Acid (3-Isopropylmalic Acid), an Intermediate in Leucine Biosynthesis^*
  作者：Joseph M. Calvo、Carl M. Stevens、M. G. Kalyanpur、H. E. Umbarger

  DOI：10.1021/bi00900a043

  日期：1964.12.1
• Micromolar Intracellular Hydrogen Peroxide Disrupts Metabolism by Damaging Iron-Sulfur Enzymes
  作者：Soojin Jang、James A. Imlay

  DOI：10.1074/jbc.m607646200

  日期：2007.1

  An Escherichia coli strain that cannot scavenge hydrogen peroxide has been used to identify the cell processes that are most sensitive to this oxidant. Low micromolar concentrations of H2O2 completely blocked the biosynthesis of leucine. The defect was tracked to the inactivation of isopropylmalate isomerase. This enzyme belongs to a family of [4Fe-4S] dehydratases that are notoriously sensitive to univalent oxidation, and experiments confirmed that other members were also inactivated. In vitro and in vivo analyses showed that H2O2 directly oxidized their solvent-exposed clusters in a Fenton-like reaction. The oxidized cluster then degraded to a catalytically inactive [3Fe-4S] form. Experiments indicated that H2O2 accepted two consecutive electrons during the oxidation event. As a consequence, hydroxyl radicals were not released; the polypeptide was undamaged; and the enzyme was competent for reactivation by repair processes. Strikingly, in scavenger-deficient mutants, the H2O2 that was generated as an adventitious by-product of metabolism (< 1 mu M) was sufficient to damage these [4Fe-4S] enzymes. This result demonstrates that aerobic organisms must synthesize H2O2 scavengers to avoid poisoning their own pathways. The extreme vulnerability of these enzymes may explain why many organisms, including mammals, deploy H2O2 to suppress microbial growth.
• The Biosynthesis of Leucine. II. The Enzymic Isomerization of β-Carboxy-β-Hydroxyisocaproate and α-Hydroxy-β-Carboxyisocaproate^*
  作者：S. R. Gross、R. O. Burns、H. E. Umbarger

  DOI：10.1021/bi00905a023

  日期：1963.9.1
• Absolute configuration of α-isopropylmalate and the mechanism of its conversion to β-isopropylmalate in the biosynthesis of leucine
  作者：Frank E. Cole、M. G. Kalyanpur、C. M. Stevens

  DOI：10.1021/bi00741a031

  日期：1973.8.1