Gondoate

• 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: Gondoate
• 英文别名: (Z)-icos-11-enoate
• 化学式: C20H37O2-
• 分子量: 309.5
• InChiKey: BITHHVVYSMSWAG-KTKRTIGZSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  22
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  40.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  水 、 N-(11Z)-icosenoylsphingosine 生成 Gondoate 、 Sphingosine(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

• Fatty acid amide hydrolase substrate specificity
  作者：Dale L Boger、Robert A Fecik、Jean E Patterson、Hiroshi Miyauchi、Matthew P Patricelli、Benjamin F Cravatt

  DOI：10.1016/s0960-894x(00)00528-x

  日期：2000.12

  Fatty acid amide hydrolase (FAAH), also referred to as oleamide hydrolase and anandamide amidohydrolase, is a serine hydrolase responsible for the degradation of endogenous oleamide and anandamide, fatty acid amides that function as chemical messengers. FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural

  脂肪酸酰胺水解酶（FAAH），也称为油酰胺水解酶和阿南酰胺酰胺水解酶，是一种丝氨酸水解酶，负责降解内源性油酰胺和阿南酰胺（充当化学信使的脂肪酸酰胺）。FAAH水解多种脂肪酸酰胺，本研究使用纯重组大鼠FAAH检查了各种天然和非天然脂肪酸伯酰胺底物的相对水解速率。
• Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids
  作者：Alaumy Joshi、Minhaj Shaikh、Shubham Singh、Abinaya Rajendran、Amol Mhetre、Siddhesh S. Kamat

  DOI：10.1074/jbc.ra118.005640

  日期：2018.11

  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.
• 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.