N-(11Z)-icosenoylphytosphingosine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 英文名称: N-(11Z)-icosenoylphytosphingosine
• 英文别名: (Z)-N-[(2S,3S,4R)-1,3,4-trihydroxyoctadecan-2-yl]icos-11-enamide
• 化学式: C₃₈H₇₅NO₄
• 分子量: 610.0
• InChiKey: UEUNBXJMEZPARB-AFKJKPLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.5
• 重原子数：
  43
• 可旋转键数：
  34
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  水 、 N-(11Z)-icosenoylphytosphingosine 生成 Gondoate 、 Phytosphingosine(1+)
  参考文献：
  名称：

  Alkaline Ceramidase 3 (ACER3) Hydrolyzes Unsaturated Long-chain Ceramides, and Its Down-regulation Inhibits Both Cell Proliferation and Apoptosis

  摘要：

  Ceramides with different fatty acyl chains may vary in their physiological or pathological roles; however, it remains unclear how cellular levels of individual ceramide species are regulated. Here, we demonstrate that our previously cloned human alkaline ceramidase 3 (ACER3) specifically controls the hydrolysis of ceramides carrying unsaturated long acyl chains, unsaturated long-chain (ULC) ceramides. In vitro, ACER3 only hydrolyzed C-18:1-, C-20:1-, C-20:4-ceramides, dihydroceramides, and phytoceramides. In cells, ACER3 overexpression decreased C-18:1- and C-20:1-ceramides and dihydroceramides, whereas ACER3 knockdown by RNA interference had the opposite effect, suggesting that ACER3 controls the catabolism of ULC ceramides and dihydroceramides. ACER3 knockdown inhibited cell proliferation and up-regulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1). Blocking p21(CIP1/WAF1) up-regulation attenuated the inhibitory effect of ACER3 knockdown on cell proliferation, suggesting that ACER3 knockdown inhibits cell proliferation because of p21(CIP1/WAF1) up-regulation. ACER3 knockdown inhibited cell apoptosis in response to serum deprivation. ACER3 knockdown up-regulated the expression of the alkaline ceramidase 2 (ACER2), and the ACER2 up-regulation decreased non-ULC ceramide species while increasing both sphingosine and its phosphate. Collectively, these data suggest that ACER3 catalyzes the hydrolysis of ULC ceramides and dihydroceramides and that ACER3 coordinates with ACER2 to regulate cell proliferation and survival.

  DOI：

  10.1074/jbc.m109.063586

文献信息

• CERAMIDE DERIVATIVES AS MODULATORS OF IMMUNITY AND AUTOIMMUNITY
  申请人：ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY

  公开号：EP1784196B1

  公开（公告）日：2016-12-21
• Alkaline Ceramidase 3 (ACER3) Hydrolyzes Unsaturated Long-chain Ceramides, and Its Down-regulation Inhibits Both Cell Proliferation and Apoptosis
  作者：Wei Hu、Ruijuan Xu、Wei Sun、Zdzislaw M. Szulc、Jacek Bielawski、Lina M. Obeid、Cungui Mao

  DOI：10.1074/jbc.m109.063586

  日期：2010.3

  Ceramides with different fatty acyl chains may vary in their physiological or pathological roles; however, it remains unclear how cellular levels of individual ceramide species are regulated. Here, we demonstrate that our previously cloned human alkaline ceramidase 3 (ACER3) specifically controls the hydrolysis of ceramides carrying unsaturated long acyl chains, unsaturated long-chain (ULC) ceramides. In vitro, ACER3 only hydrolyzed C-18:1-, C-20:1-, C-20:4-ceramides, dihydroceramides, and phytoceramides. In cells, ACER3 overexpression decreased C-18:1- and C-20:1-ceramides and dihydroceramides, whereas ACER3 knockdown by RNA interference had the opposite effect, suggesting that ACER3 controls the catabolism of ULC ceramides and dihydroceramides. ACER3 knockdown inhibited cell proliferation and up-regulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1). Blocking p21(CIP1/WAF1) up-regulation attenuated the inhibitory effect of ACER3 knockdown on cell proliferation, suggesting that ACER3 knockdown inhibits cell proliferation because of p21(CIP1/WAF1) up-regulation. ACER3 knockdown inhibited cell apoptosis in response to serum deprivation. ACER3 knockdown up-regulated the expression of the alkaline ceramidase 2 (ACER2), and the ACER2 up-regulation decreased non-ULC ceramide species while increasing both sphingosine and its phosphate. Collectively, these data suggest that ACER3 catalyzes the hydrolysis of ULC ceramides and dihydroceramides and that ACER3 coordinates with ACER2 to regulate cell proliferation and survival.