甘油磷脂生物合成
中文名称
通路描述
甘油磷脂是生物膜结构和功能的重要成分，也是血清脂蛋白和肺表面活性剂的组成部分。此外，甘油磷脂还作为脂质介质的前体，如血小板活化因子和前列腺素。细胞膜含有各种甘油磷脂的特定组成，包括磷脂酸（PA）、磷脂酰胆碱（PC）、磷脂酰乙醇胺（PE）、磷脂酰丝氨酸（PS）、磷脂酰甘油（PG）、磷脂酰肌醇（PI）、心磷脂（CL）、磷脂酰肌醇二酰基（LPA）和磷脂酰肌醇二酰基（BMP）。
甘油磷脂首先通过 从头（Kennedy）途径形成，使用脂肪酸作为酰基-CoA供体。然而，甘油磷脂的酰基基团高度多样化，并以不对称方式分布。饱和和单不饱和脂肪酸通常酯化在 sn-1 位点，而多不饱和酰基基团酯化在 sn-2 位点。随后的酰基链重塑（Lands 循环）生成细胞膜特征性的多样性和不对称性。
在甘油磷脂生物合成的 从头途径中，磷脂酰肌醇（LPA）最初由甘油 3-磷酸（G3P）形成。随后，LPA 由磷脂酰肌醇酰转移酶（AGPAT，也称为 LPAAT）转化为 PA，然后 PA 代谢为两种类型的甘油衍生物。第一种是二酰甘油（DAG），转化为三酰甘油（TAG）、PC 和 PE。随后，PS 从 PC 或 PE 合成。第二种是胞苷二磷酸 - 二酰甘油（CDP-DAG），被处理为 PI、PG、CL 和 BMP。每种甘油磷脂都通过磷脂酶裂解后由酰基转移酶重新酰基化参与酰基链重塑。
大多数甘油磷脂在内质网（ER）中合成，但一些，特别是心磷脂和 BMP，分别在线粒体和内体膜中合成。由于大多数甘油磷脂存在于所有膜 compartments，因此必须存在广泛的甘油磷脂从一种膜 compartment 到另一种膜 compartment 运输的网络，通过各种机制，包括通过细胞质扩散、形成运输复合物以及通过膜接触位点（MCS）扩散（Osman 等 2011，Lebiedzinska 等 2009，Lev 2010，Scherer 和 Schmitz 2011，Orso 等 2011，Hermansson 等 2011，Vance 和 Vance 2008）。
甘油磷脂首先通过 从头（Kennedy）途径形成，使用脂肪酸作为酰基-CoA供体。然而，甘油磷脂的酰基基团高度多样化，并以不对称方式分布。饱和和单不饱和脂肪酸通常酯化在 sn-1 位点，而多不饱和酰基基团酯化在 sn-2 位点。随后的酰基链重塑（Lands 循环）生成细胞膜特征性的多样性和不对称性。
在甘油磷脂生物合成的 从头途径中，磷脂酰肌醇（LPA）最初由甘油 3-磷酸（G3P）形成。随后，LPA 由磷脂酰肌醇酰转移酶（AGPAT，也称为 LPAAT）转化为 PA，然后 PA 代谢为两种类型的甘油衍生物。第一种是二酰甘油（DAG），转化为三酰甘油（TAG）、PC 和 PE。随后，PS 从 PC 或 PE 合成。第二种是胞苷二磷酸 - 二酰甘油（CDP-DAG），被处理为 PI、PG、CL 和 BMP。每种甘油磷脂都通过磷脂酶裂解后由酰基转移酶重新酰基化参与酰基链重塑。
大多数甘油磷脂在内质网（ER）中合成，但一些，特别是心磷脂和 BMP，分别在线粒体和内体膜中合成。由于大多数甘油磷脂存在于所有膜 compartments，因此必须存在广泛的甘油磷脂从一种膜 compartment 到另一种膜 compartment 运输的网络，通过各种机制，包括通过细胞质扩散、形成运输复合物以及通过膜接触位点（MCS）扩散（Osman 等 2011，Lebiedzinska 等 2009，Lev 2010，Scherer 和 Schmitz 2011，Orso 等 2011，Hermansson 等 2011，Vance 和 Vance 2008）。
英文描述
Glycerophospholipid biosynthesis Glycerophospholipids are important structural and functional components of biological membranes and constituents of serum lipoproteins and the pulmonary surfactant. In addition, glycerophospholipids act as precursors of lipid mediators such as platelet-activating factor and eicosanoids. Cellular membranes contains a distinct composition of various glycerophospholipids such as phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), cardiolipin (CL), lysophosphatidic acid (LPA) and lysobisphosphatidic acid (also known as bis(monoacylglycerol) hydrogen phosphate - BMP).
Glycerophospholipids are first formed by the de novo (Kennedy) pathway using fatty acids activated as acyl-CoA donors. However, the acyl groups of glycerophospholipids are highly diverse and distributed in an asymmetric manner. Saturated and monounsaturated fatty acids are usually esterified at the sn-1 position, whereas polyunsaturated acyl groups are esterified at the sn-2 position. Subsequent acyl chain remodeling (Lands cycle) generates the diverse glycerophospholipid composition and asymmetry characteristic of cell membranes.
In the de novo pathway of glycerophospholipid biosynthesis, lysophosphatidic acid (LPA) is initially formed from glycerol 3-phosphate (G3P). Next, LPA is converted to PA by a LPA acyltransferase (AGPAT, also known as LPAAT), then PA is metabolized into two types of glycerol derivatives. The first is diacylglycerol (DAG) which is converted to triacylglycerol (TAG), PC, and PE. Subsequently, PS is synthesized from PC or PE. The second is cytidine diphosphate-diacylglycerol (CDP-DAG), which is processed into PI, PG, CL, and BMP. Each glycerophospholipid is involved in acyl chain remodeling via cleavage by phospholipases followed by reacylation by an acyltransferase.
Most of the glycerophospholipids are synthesized at the endoplasmic reticulum (ER), however, some, most notably cardiolipin, and BMP are synthesized in the mitochondrial and endosomal membranes respectively. Since the most of the glycerophospholipids are found in all membrane compartments, there must be extensive network of transport of glycerophospholipids from one membrane compartment to another via various mechanisms including diffusion through the cytosol, formation of transportation complexes, and diffusion via membrane contact sites (MCS) (Osman et al. 2011, Lebiedzinska et al. 2009, Lev 2010, Scherer & Schmitz 2011, Orso et al. 2011, Hermansson et al. 2011, Vance & Vance 2008).
Glycerophospholipids are first formed by the de novo (Kennedy) pathway using fatty acids activated as acyl-CoA donors. However, the acyl groups of glycerophospholipids are highly diverse and distributed in an asymmetric manner. Saturated and monounsaturated fatty acids are usually esterified at the sn-1 position, whereas polyunsaturated acyl groups are esterified at the sn-2 position. Subsequent acyl chain remodeling (Lands cycle) generates the diverse glycerophospholipid composition and asymmetry characteristic of cell membranes.
In the de novo pathway of glycerophospholipid biosynthesis, lysophosphatidic acid (LPA) is initially formed from glycerol 3-phosphate (G3P). Next, LPA is converted to PA by a LPA acyltransferase (AGPAT, also known as LPAAT), then PA is metabolized into two types of glycerol derivatives. The first is diacylglycerol (DAG) which is converted to triacylglycerol (TAG), PC, and PE. Subsequently, PS is synthesized from PC or PE. The second is cytidine diphosphate-diacylglycerol (CDP-DAG), which is processed into PI, PG, CL, and BMP. Each glycerophospholipid is involved in acyl chain remodeling via cleavage by phospholipases followed by reacylation by an acyltransferase.
Most of the glycerophospholipids are synthesized at the endoplasmic reticulum (ER), however, some, most notably cardiolipin, and BMP are synthesized in the mitochondrial and endosomal membranes respectively. Since the most of the glycerophospholipids are found in all membrane compartments, there must be extensive network of transport of glycerophospholipids from one membrane compartment to another via various mechanisms including diffusion through the cytosol, formation of transportation complexes, and diffusion via membrane contact sites (MCS) (Osman et al. 2011, Lebiedzinska et al. 2009, Lev 2010, Scherer & Schmitz 2011, Orso et al. 2011, Hermansson et al. 2011, Vance & Vance 2008).
所含基因
6 个基因