1-Palmitoyl-2-(5-hydroxyvaleroyl)-sn-glycero-3-phosphocholine | 344764-51-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 英文名称: 1-Palmitoyl-2-(5-hydroxyvaleroyl)-sn-glycero-3-phosphocholine
• 英文别名: [(2R)-3-hexadecanoyloxy-2-(5-hydroxypentanoyloxy)propyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 344764-51-8
• 化学式: C₂₉H₅₈NO₉P
• 分子量: 595.755
• InChiKey: SDMRQBYTTVCDFR-HHHXNRCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  30
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-花生四烯酰-1-棕榈酰-sn-甘油-3-磷酸胆碱 在 氧气 、 rat voltage-gated potassium channel β-subunit 、 还原型辅酶II(NADPH)四钠盐 作用下， 反应 94.0h， 生成 1-Palmitoyl-2-(5-hydroxyvaleroyl)-sn-glycero-3-phosphocholine 、 、
  参考文献：
  名称：

  Catalytic reduction of carbonyl groups in oxidized PAPC by Kvβ2 (AKR6)

  摘要：

  The beta-subunits of the voltage-gated potassium channel (Kv beta) belong to the aldo-keto reductase superfamily. The Kv beta-subunits dock with the pore-forming Kv alpha-subunits and impart or accelerate the rate of inactivation in Kv channels. Inactivation of Kv currents by Kv beta is differentially regulated by oxidized and reduced pyridine nucleotides. In mammals, AKR6 family is comprised of 3 different genes Kv beta 1-3. We have shown previously that Kv beta 2 catalyzes the reduction of a broad range of carbonyls including aromatic carbonyls, electrophilic aldehydes and prostaglandins. However, the endogenous substrates for Kv beta have not been identified. To determine whether products of lipid oxidation are substrates of Kv beta s, we tested the enzymatic activity of Kv beta 2 with oxidized phospholipids generated during the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC). Electrospray ionization mass spectrometric analysis showed that Kv beta 2 catalyzed the NADPH-dependent reduction of several products of oxPAPC, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC), 1-palmitoyl-2-(epoxycyclopentenone)-sn-glycero-3-phosphorylcholine (PECPC), 1-palmitoyl-2-(5,6)- epoxyisoprostane E2-sn-glycero-3-phosphocholine (PEIPC). These results were validated using high resolution mass spectrometric analysis. Time course analysis revealed that the reduced products reached significant levels for ions at m/z 594/596 (POVPC/PHVPC), 810/812 (PECPC/2H-PECPC) and 828/830 (PEIPC/2H-PEIPC) in the oxPAPC + Kv beta 2 mixture (p < 0.01). These results suggest that Kv beta could serve as a sensor of lipid oxidation via its catalytic activity and thereby alter Kv currents under conditions of oxidative stress. (C) 2011 Published by Elsevier Ireland Ltd.

  DOI：

  10.1016/j.cbi.2011.01.032

文献信息

• Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes
  作者：Matthew Spite、Shahid P. Baba、Yonis Ahmed、Oleg A. Barski、Kanchan Nijhawan、J. Mark Petrash、Aruni Bhatnagar、Sanjay Srivastava

  DOI：10.1042/bj20061743

  日期：2007.7.1

  Phospholipid oxidation generates several bioactive aldehydes that remain esterified to the glycerol backbone (‘core’ aldehydes). These aldehydes induce endothelial cells to produce monocyte chemotactic factors and enhance monocyte–endothelium adhesion. They also serve as ligands of scavenger receptors for the uptake of oxidized lipoproteins or apoptotic cells. The biochemical pathways involved in phospholipid aldehyde metabolism, however, remain largely unknown. In the present study, we have examined the efficacy of the three mammalian AKR (aldo-keto reductase) families in catalysing the reduction of phospholipid aldehydes. The model phospholipid aldehyde POVPC [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine] was efficiently reduced by members of the AKR1, but not by the AKR6 or the ARK7 family. In the AKR1 family, POVPC reductase activity was limited to AKR1A and B. No significant activity was observed with AKR1C enzymes. Among the active proteins, human AR (aldose reductase) (AKR1B1) showed the highest catalytic activity. The catalytic efficiency of human small intestinal AR (AKR1B10) was comparable with the murine AKR1B proteins 1B3 and 1B8. Among the murine proteins AKR1A4 and AKR1B7 showed appreciably lower catalytic activity as compared with 1B3 and 1B8. The human AKRs, 1B1 and 1B10, and the murine proteins, 1B3 and 1B8, also reduced C-7 and C-9 sn-2 aldehydes as well as POVPE [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphoethanolamine]. AKR1A4, B1, B7 and B8 catalysed the reduction of aldehydes generated in oxidized C16:0-20:4 phosphatidylcholine with acyl, plasmenyl or alkyl linkage at the sn-1 position or C16:0-20:4 phosphatidylglycerol or phosphatidic acid. AKR1B1 displayed the highest activity with phosphatidic acids; AKR1A4 was more efficient with long-chain aldehydes such as 5-hydroxy-8-oxo-6-octenoyl derivatives, whereas AKR1B8 preferred phosphatidylglycerol. These results suggest that proteins of the AKR1A and B families are efficient phospholipid aldehyde reductases, with non-overlapping substrate specificity, and may be involved in tissue-specific metabolism of endogenous or dietary phospholipid aldehydes.

  磷脂氧化会产生几种生物活性醛，这些醛仍然酯化在甘油骨架上（"核心 "醛）。这些醛会诱导内皮细胞产生单核细胞趋化因子，并增强单核细胞与内皮细胞的粘附性。它们还是清道夫受体的配体，用于吸收氧化脂蛋白或凋亡细胞。然而，磷脂醛代谢所涉及的生化途径在很大程度上仍不为人所知。在本研究中，我们考察了三种哺乳动物 AKR（醛酮还原酶）家族催化磷脂醛还原的功效。模型磷脂醛 POVPC [1-棕榈酰-2-（5-氧代戊酰基）-sn-甘油-3-磷酰基胆碱] 可被 AKR1 家族成员有效还原，但 AKR6 或 ARK7 家族成员则无法还原。在 AKR1 家族中，POVPC 还原酶的活性仅限于 AKR1A 和 B。在活性蛋白中，人AR（醛糖还原酶）（AKR1B1）的催化活性最高。人小肠 AR（AKR1B10）的催化效率与鼠 AKR1B 蛋白 1B3 和 1B8 相当。在小鼠蛋白中，AKR1A4 和 AKR1B7 的催化活性明显低于 1B3 和 1B8。人类 AKRs 1B1 和 1B10 以及鼠类蛋白 1B3 和 1B8 还能还原 C-7 和 C-9 sn-2 醛类以及 POVPE [1-棕榈酰-2-（5-氧代戊酰基）-sn-甘油-3-磷脂酰乙醇胺]。AKR1A4、B1、B7 和 B8 催化氧化 C16:0-20:4 磷脂酰胆碱（Sn-1 位上有酰基、质子酰基或烷基连接）或 C16:0-20:4 磷脂酰甘油或磷脂酸中生成的醛的还原。AKR1B1 对磷脂酸的活性最高；AKR1A4 对长链醛（如 5-hydroxy-8-oxo-6-octenoyl 衍生物）的活性更高，而 AKR1B8 则更喜欢磷脂酰甘油。这些结果表明，AKR1A 和 B 家族的蛋白质是高效的磷脂醛还原酶，具有不重叠的底物特异性，可能参与了内源性或食物磷脂醛的组织特异性代谢。
• Aldose Reductase-catalyzed Reduction of Aldehyde Phospholipids
  作者：Sanjay Srivastava、Matthew Spite、John O. Trent、Matthew B. West、Yonis Ahmed、Aruni Bhatnagar

  DOI：10.1074/jbc.m403416200

  日期：2004.12

  Oxidation of unsaturated phospholipids results in the generation of aldehyde side chains that remain esterified to the phospholipid backbone. Such "core" aldehydes elicit immune responses and promote inflammation. However, the biochemical mechanisms by which phospholipid aldehydes are metabolized or detoxified are not well understood. In the studies reported here, we examined whether aldose reductase (AR), which reduces hydrophobic aldehydes, metabolizes phospholipid aldehydes. Incubation with AR led to the reduction of 5-oxovaleroyl, 7-oxo-5-heptenoyl, 5-hydroxy-6-oxo-caproyl, and 5-hydroxy-8-oxo-6-octenoyl phospholipids generated upon oxidation of 1-palmitoyl-2-arachidonoyl-sn- glycero-3-phosphocholine (PAPC). The enzyme also catalyzed the reduction of phospholipid aldehydes generated from the oxidation of 1-alkyl, and 1-alkenyl analogs of PAPC, and 1-palmitoyl-2-arachidonoyl phosphatidic acid or phosphoglycerol. Aldose reductase catalyzed the reduction of chemically synthesized 1-palmitoyl-2-( 5-oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) with a K-m of 10 muM. Addition of POVPC to the culture medium led to incorporation and reduction of the aldehyde in COS-7 and THP-1 cells. Reduction of POVPC in these cells was prevented by the AR inhibitors sorbinil and tolrestat and was increased in COS-7 cells overexpressing AR. Together, these observations suggest that AR may be a significant participant in the metabolism of several structurally diverse phospholipid aldehydes. This metabolism may be a critical regulator of the pro-inflammatory and immunogenic effects of oxidized phospholipids.
• Catalytic reduction of carbonyl groups in oxidized PAPC by Kvβ2 (AKR6)
  作者：Zhengzhi Xie、Oleg A. Barski、Jian Cai、Aruni Bhatnagar、Srinivas M. Tipparaju

  DOI：10.1016/j.cbi.2011.01.032

  日期：2011.5

  The beta-subunits of the voltage-gated potassium channel (Kv beta) belong to the aldo-keto reductase superfamily. The Kv beta-subunits dock with the pore-forming Kv alpha-subunits and impart or accelerate the rate of inactivation in Kv channels. Inactivation of Kv currents by Kv beta is differentially regulated by oxidized and reduced pyridine nucleotides. In mammals, AKR6 family is comprised of 3 different genes Kv beta 1-3. We have shown previously that Kv beta 2 catalyzes the reduction of a broad range of carbonyls including aromatic carbonyls, electrophilic aldehydes and prostaglandins. However, the endogenous substrates for Kv beta have not been identified. To determine whether products of lipid oxidation are substrates of Kv beta s, we tested the enzymatic activity of Kv beta 2 with oxidized phospholipids generated during the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC). Electrospray ionization mass spectrometric analysis showed that Kv beta 2 catalyzed the NADPH-dependent reduction of several products of oxPAPC, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC), 1-palmitoyl-2-(epoxycyclopentenone)-sn-glycero-3-phosphorylcholine (PECPC), 1-palmitoyl-2-(5,6)- epoxyisoprostane E2-sn-glycero-3-phosphocholine (PEIPC). These results were validated using high resolution mass spectrometric analysis. Time course analysis revealed that the reduced products reached significant levels for ions at m/z 594/596 (POVPC/PHVPC), 810/812 (PECPC/2H-PECPC) and 828/830 (PEIPC/2H-PEIPC) in the oxPAPC + Kv beta 2 mixture (p < 0.01). These results suggest that Kv beta could serve as a sensor of lipid oxidation via its catalytic activity and thereby alter Kv currents under conditions of oxidative stress. (C) 2011 Published by Elsevier Ireland Ltd.