(R)-2-hydroxy-stearoyl-CoA

• 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: (R)-2-hydroxy-stearoyl-CoA
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-[[[[(3R)-3-hydroxy-4-[[3-[2-[(2R)-2-hydroxyoctadecanoyl]sulfanylethylamino]-3-oxopropyl]amino]-2,2-dimethyl-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]oxolan-3-yl] phosphate
• 化学式: C39H66N7O18P3S-4
• 分子量: 1046.0
• InChiKey: OJQMIXCIJFLULT-MXQBTARFSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  68
• 可旋转键数：
  35
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  421
• 氢给体数：
  6
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  (R)-2-hydroxy-stearoyl-CoA 生成 formyl-coenzyme A 、 十七碳醛
  参考文献：
  名称：

  The role of 2-hydroxyacyl-CoA lyase, a thiamin pyrophosphate-dependent enzyme, in the peroxisomal metabolism of 3-methyl-branched fatty acids and 2-hydroxy straight-chain fatty acids

  摘要：

  2-Hydroxyphytanoyl-CoA lyase（缩写为 2-HPCL），后更名为 2-hydroxyacyl-CoA lyase（缩写为 HACL1），是哺乳动物中第一个被发现依赖于 TPP（焦磷酸硫胺素）的过氧化物酶。它是在 1999 年研究植烷酸的α-氧化作用时发现的。HACL1 至少在两个途径中发挥重要作用：(i) 降解植烷酸等 3-甲基支链脂肪酸；(ii) 缩短 2-羟基长链脂肪酸。在这两种情况下，HACL1 都会催化裂解步骤，裂解过程中，2-羟基乙酰-CoA 中间体的第一个碳原子和第二个碳原子之间的碳-碳键发生分裂，产生 (n-1) 醛和甲酰基-CoA。后者迅速转化为甲酸，随后转化为 CO2。HACL1 是一种同源四聚体，其 C 端有一个 PTS（过氧化物酶体靶向信号）（PTS1）。人类尚未发现 HACL1 缺乏症，但硫胺素缺乏可能会影响其活性。

  DOI：

  10.1042/bst0350876

文献信息

• Breakdown of 2-Hydroxylated Straight Chain Fatty Acids via Peroxisomal 2-Hydroxyphytanoyl-CoA Lyase
  作者：Veerle Foulon、Mieke Sniekers、Els Huysmans、Stanny Asselberghs、Vincent Mahieu、Guy P. Mannaerts、Paul P. Van Veldhoven、Minne Casteels

  DOI：10.1074/jbc.m413362200

  日期：2005.3

  Hydroxyfatty acids, constituents of brain cerebro-sides and sulfatides, were previously reported to be degraded by an alpha-oxidation system, generating fatty acids shortened by one carbon atom. In the current study we used labeled and unlabeled 2-hydroxyoctadecanoic acid to reinvestigate the degradation of this class of lipids. Both in intact and broken cell systems formate was identified as a main reaction product. Furthermore, the generation of an n-1 aldehyde was demonstrated. In permeabilized rat hepatocytes and liver homogenates, studies on cofactor requirements revealed a dependence on ATP, CoA, Mg2+, thiamine pyrophosphate, and NAD(+). Together with subcellular fractionation data and studies on recombinant enzymes, this led to the following picture. In a first step, the 2-hydroxyfatty acid is activated to an acyl-CoA; subsequently, the 2-hydroxy fatty acyl-CoA is cleaved by 2-hydroxyphytanoyl-CoA lyase, to formyl-CoA and an n-1 aldehyde. The severe inhibition of formate generation by oxythiamin treatment of intact fibroblasts indicates that cleavage through the thiamine pyrophosphate-dependent 2-hydroxyphytanoyl-CoA lyase is the main pathway for the degradation of 2-hydroxyfatty acids. The latter protein was initially characterized as an essential enzyme in the peroxisomal alpha-oxidation of 3-methyl-branched fatty acids such as phytanic acid. Our findings point to a new role for peroxisomes in mammals, i.e. the breakdown of 2-hydroxyfatty acids, at least the long chain 2-hydroxyfatty acids. Most likely, the more abundant very long chain 2-hydroxyfatty acids are degraded in a similar manner.