4-amino-6-oxohexanoic acid hydrochloride | 137465-14-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-amino-6-oxohexanoic acid hydrochloride
• 英文别名: 4-Amino-6-oxohexanoic acid;hydrochloride；4-amino-6-oxohexanoic acid;hydrochloride
• CAS: 137465-14-6
• 化学式: C₆H₁₁NO₃*ClH
• 分子量: 181.619
• InChiKey: UNAIEOQLADCNPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.19
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  80.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-allylpyrrolidin-2-one 在 盐酸 、 lithium hydroxide 、 臭氧 作用下， 反应 3.33h， 生成 4-amino-6-oxohexanoic acid hydrochloride
  参考文献：
  名称：

  Mechanism of inactivation of .gamma.-aminobutyric acid aminotransferase by 4-amino-5-hexynoic acid (.gamma.-ethynyl GABA)

  摘要：

  Gamma-Aminobutyric acid (GABA) aminotransferase is a pyridoxal phosphate (PLP) dependent enzyme that catalyzes the degradation of gamma-aminobutyric acid. The inactivation of GABA aminotransferase has been shown to be an important treatment for epilepsy. The mechanism of inactivation of GABA aminotransferase by gamma-ethynyl GABA, a mechanism-based inactivator of GABA aminotransferase that shows anticonvulsant activity in animal models, is investigated in this paper. Although it appears that azaallylic isomerization (the normal catalytic pathway for substrates) of the PLP-bound inactivator occurs (pathway a, Scheme VII), little or no inactivation of the enzyme results from that isomerization. Essentially all of the inactivation is derived from a propargylic isomerization (pathway b) to the allenamine bound PLP adduct 10, which undergoes nucleophilic attack at two different sites. It appears that an active site lysine residue reacts at the Schiff base to give the free enamine 18 (pathway c) or reacts at the allene to give the enzyme and cofactor bound enamine 12 (pathway d); possible attack by water (pathway e) would lead to metabolite 26. The enamine 18 does not become attached to the PLP (Scheme III, pathway a), but a small amount (5-10%) may become attached to the enzyme at a site other than at lysine (9, Scheme III, pathway b). Adduct 9 also could be derived from azaallylic isomerization of the inactivator-PLP Schiff base followed by conjugate addition to the acetylene by an active site nucleophile other than a lysine residue (Scheme I). Mostly 18 is released into solution to give 27 (Scheme VII). Adduct 12 is believed to be a transient intermediate that partitions between conversion to metabolite 26 (Scheme VII, pathway f) and conversion to a more stable isomer (13, pathway g). Upon denaturation, adduct 13 partitions equally (Scheme VIII) between release of metabolite 26 and the formation of another covalent adduct (17). Isolation and identification of the amine and nonamine metabolites produced during processing of gamma-ethynyl GABA showed that, on average, for every 13 molecules of gamma-ethynyl GABA that are turned over, 1.2 undergoes transamination (pathway a, Scheme VII), 2.6 are metabolized to 27 (pathways b and c), 8.2 are converted to 26 (pathways b, d, and f and/or pathways b and e), and 1.0 becomes attached to the enzyme, almost all, as 13 (pathways b, d, and g), but possibly 5-10% as 9 (X not-equal Lys) as discussed above.

  DOI：

  10.1021/ja00024a042

文献信息

• Mechanism of inactivation of .gamma.-aminobutyric acid aminotransferase by 4-amino-5-hexynoic acid (.gamma.-ethynyl GABA)
  作者：James R. Burke、Richard B. Silverman

  DOI：10.1021/ja00024a042

  日期：1991.11

  Gamma-Aminobutyric acid (GABA) aminotransferase is a pyridoxal phosphate (PLP) dependent enzyme that catalyzes the degradation of gamma-aminobutyric acid. The inactivation of GABA aminotransferase has been shown to be an important treatment for epilepsy. The mechanism of inactivation of GABA aminotransferase by gamma-ethynyl GABA, a mechanism-based inactivator of GABA aminotransferase that shows anticonvulsant activity in animal models, is investigated in this paper. Although it appears that azaallylic isomerization (the normal catalytic pathway for substrates) of the PLP-bound inactivator occurs (pathway a, Scheme VII), little or no inactivation of the enzyme results from that isomerization. Essentially all of the inactivation is derived from a propargylic isomerization (pathway b) to the allenamine bound PLP adduct 10, which undergoes nucleophilic attack at two different sites. It appears that an active site lysine residue reacts at the Schiff base to give the free enamine 18 (pathway c) or reacts at the allene to give the enzyme and cofactor bound enamine 12 (pathway d); possible attack by water (pathway e) would lead to metabolite 26. The enamine 18 does not become attached to the PLP (Scheme III, pathway a), but a small amount (5-10%) may become attached to the enzyme at a site other than at lysine (9, Scheme III, pathway b). Adduct 9 also could be derived from azaallylic isomerization of the inactivator-PLP Schiff base followed by conjugate addition to the acetylene by an active site nucleophile other than a lysine residue (Scheme I). Mostly 18 is released into solution to give 27 (Scheme VII). Adduct 12 is believed to be a transient intermediate that partitions between conversion to metabolite 26 (Scheme VII, pathway f) and conversion to a more stable isomer (13, pathway g). Upon denaturation, adduct 13 partitions equally (Scheme VIII) between release of metabolite 26 and the formation of another covalent adduct (17). Isolation and identification of the amine and nonamine metabolites produced during processing of gamma-ethynyl GABA showed that, on average, for every 13 molecules of gamma-ethynyl GABA that are turned over, 1.2 undergoes transamination (pathway a, Scheme VII), 2.6 are metabolized to 27 (pathways b and c), 8.2 are converted to 26 (pathways b, d, and f and/or pathways b and e), and 1.0 becomes attached to the enzyme, almost all, as 13 (pathways b, d, and g), but possibly 5-10% as 9 (X not-equal Lys) as discussed above.