1、二、 其他脂类的生物合成,Biosynthesis of phosphatidic acid. A fatty acyl group is activated by formation of the fatty acylCoA, then transferred to ester linkage with L-glycerol 3-phosphate, formed in either of the two ways shown. Phosphatidic acid is shown here with the correct stereochemistry at C-2 of the gly
2、cerol molecule. To conserve space in subsequent figures, both fatty acyl groups of glycerophospholipids, and all three acyl groups of triacylglycerols, are shown projecting to the right.,Phosphatidic acid in lipid biosynthesis. Phosphatidic acid is the precursor of both triacylglycerols and glycerop
3、hospholipids. The mechanisms for head-group attachment in phospholipid synthesis are described later in this section.,1.三酰甘油的合成,Some of the fatty acids released into the blood are used for energy (in muscle, for example), and some are taken up by the liver and used in triacylglycerol synthesis. The
4、triacylglycerol formed in the liver is transported in the blood back to adipose tissue, where the fatty acid is released by extracellular lipoprotein lipase, taken up by adipocytes, and reesterified,The triacylglycerol cycle. In mammals, triacylglycerol molecules are broken down and resynthesized in
5、 a triacylglycerol cycle during starvation. Some of the fatty acids released by lipolysis of triacylglycerol in adipose tissue pass into the bloodstream, and the remainder are used for resynthesis of triacylglycerol.,Insulin stimulates conversion of dietary carbohydrates and proteins to fat. Individ
6、uals with diabetes mellitus lack insulin; in uncontrolled disease, this results in diminished fatty acid synthesis, and the acetyl-CoA arising from catabolism of carbohydrates and proteins is shunted instead to ketone body production. People in severe ketosis smell of acetone, so the condition is so
7、metimes mistaken for drunkenness.,Regulation of triacylglycerol synthesis by insulin,Glyceroneogenesis. The pathway is essentially an abbreviated version of gluconeogenesis, from pyruvate to dihydroxyacetone phosphate (DHAP), followed by conversion of DHAP to glycerol 3-phosphate, which is used for
8、the synthesis of triacylglycerol.,Regulation of glyceroneogenesis. (a) Glucocorticoid hormones stimulate glyceroneogenesis and gluconeogenesis in the liver, while suppressing glyceroneogenesis in the adipose tissue (by reciprocal regulation of the gene expressing PEP carboxykinase (PEPCK) in the two
9、 tissues); this increases the flux through the triacylglycerol cycle.,The glycerol freed by the breakdown of triacylglycerol in adipose tissue is released to the blood and transported to the liver, where it is primarily converted to glucose, although some is converted to glycerol 3-phosphate by glyc
10、erol kinase.,Thiazolidinediones activate a nuclear receptor called peroxisome proliferator-activated receptor (PPAR), which induces the activity of PEP carboxykinase. Therapeutically, thiazolidinediones increase the rate of glyceroneogenesis, thus increasing the resynthesis of triacylglycerol in adi
11、pose tissue and reducing the amount of free fatty acid in the blood.,(b) A class of drugs called thiazolidinediones are now used to treat type 2 diabetes. In this disease, high levels of free fatty acids in the blood interfere with glucose utilization in muscle and promote insulin resistance.,2.真核细胞
12、中磷脂的合成,Two general strategies for forming the phosphodiester bond of phospholipids. In both cases, CDP supplies the phosphate group of the phosphodiester bond.,Initially, a head group (either serine or glycerol 3-phosphate) is attached via a CDPdiacylglycerol intermediate. For phospholipids other th
13、an phosphatidylserine, the head group is further modified, as shown here. In the enzyme names, PG represents phosphatidylglycerol; PS, phosphatidylserine.,Origin of the polar head groups of phospholipids in E. coli,These glycero-phospholipids are synthesized using strategy 1. Phospha-tidylglycerol i
14、s synthesized as in bacteria. PI represents phospha-tidylinositol.,Synthesis of cardiolipin and phosphatidylinositol in eukaryotes,The “salvage” pathway from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in yeast. Phosphatidylserine and phosphatidylethanolamine are interconv
15、erted by a reversible head-group exchange reaction. In mammals, phosphatidylserine is derived from phosphatidylethanolamine by a reversal of this reaction; adoMet is S-adenosylmethionine; adoHcy, Sadenosylhomocysteine.,Pathway for phosphatidylcholine synthesis from choline in mammals. The same strat
16、egy shown here (strategy 2) is also used for salvaging ethanolamine in phosphatidylethanolamine synthesis.,Summary of the pathways to phosphatidyl-choline and Phosphatidyl-ethanolamine. Conversion of phosphatidyl-ethanolamine to phosphatidyl-choline in mammals takes place only in the liver.,真核细胞中磷脂的
17、合成（综合1 ）,真核细胞中磷脂的合成（综合2）,哺乳动物磷脂酰胆碱和磷脂酰乙醇氨的相互转化,真核细胞中CDP-二酰甘油是合成磷脂酰肌醇，磷脂酰甘油，心磷脂的前体。,3.动物细胞中缩醛磷脂的合成,血小板活化因子:1-烷基-2-乙酰甘油磷酸胆碱的合成,4.鞘脂的生物合成由3-酮鞘氨醇合成酶催化的反应开始,3-酮鞘氨醇,二氢鞘氨醇,N-脂酰二氢鞘氨醇,神经酰胺,动物细胞中糖基神经酰胺，神经节苷脂和鞘磷脂的由神经酰胺合成。,鞘磷脂,5.花生四烯酸是合成前列腺素，血拴烷和白三烯的前体。,前列腺素内过氧化物合成酶催化PGH2的合成,阿斯匹林使环加氧酶失活,5.胆固醇的合成,甲羟戊酸的合成,甲羟戊酸合成的
18、机制,HMG-CoA还原酶的活力受合成速度、降解速度及磷酸化和脱磷酸调控。,甲羟戊酸到鲨烯的转化,Oxidation at C-15 converts retinol to the aldehyde, retinal (c), and further oxidation produces retinoic acid (d), a hormone that regulates gene expression. Retinal combines with the protein opsin to form rhodopsin (not shown), a visual pigment widesp
19、read in nature. In the dark, retinal of rhodopsin is in the 11-cis form (c). When a rhodopsin molecule is excited by visible light, the 11-cis-retinal undergoes a series of photochemical reactions that convert it to all-trans-retinal (e), forcing a change in the shape of the entire rhodopsin molecul
20、e. This transformation in the rod cell of the vertebrate retina sends an electrical signal to the brain that is the basis of visual transduction.,(a) -Carotene is the precursor of vitamin A1. Isoprene structural units are set off by dashed red lines. Cleavage of -carotene yields two molecules of vit
21、amin A1 (retinol) (b).,Vitamin A1 and its precursor and derivatives,由鲨烯转化为胆固醇,豆甾醇,麦角甾醇,胆固醇的合成是一个高度耗能的过程，合成一个胆固醇需18个乙酰辅酶A，36个ATP，16个NADPH。能源物质过剩时，胆固醇的合成速度加快，午夜时，合成速度较快，膳食固醇类，特别是植物固醇可抑制胆固醇的合成。,Lipoproteins. (a) Structure of a low-density lipoprotein (LDL). Apolipoprotein B-100 (apoB-100) is one of the
22、 largest single polypeptide chains known, with 4,636 amino acid residues (Mr 513,000). (b) Four classes of lipoproteins, visualized in the electron microscope after negative staining. Clockwise from top left: chylomicrons, 50 to 200 nm in diameter; VLDL, 28 to 70 nm; HDL, 8 to 11 nm; and LDL, 20 to
23、25 nm.,脂类是由脂蛋白运输的,Lipoproteins and lipid transport. (a) Lipids are transported in the bloodstream as lipoproteins, which exist as several variants that have different functions, different protein and lipid compositions, and thus different densities. Dietary lipids are packaged into chylomicrons; muc
24、h of their triacylglycerol content is released by lipoprotein lipase to adipose and muscle tissues during transport through capillaries. Chylomicron remnants (containing largely protein and cholesterol) are taken up by the liver. Endogenous lipids and cholesterol from the liver are delivered to adip
25、ose and muscle tissue by VLDL.,Extraction of lipid from VLDL (along with loss of some apolipoproteins) gradually converts some of it to LDL, which delivers cholesterol to extrahepatic tissues or returns to the liver. The liver takes up LDL, VLDL remnants, and chylomicron remnants by receptor-mediate
26、d endocytosis. Excess cholesterol in extrahepatic tissues is transported back to the liver as HDL. In the liver, some cholesterol is converted to bile salts.,(b) Blood plasma samples collected after a fast (left) and after a high-fat meal (right). Chylomicrons produced after a fatty meal give the pl
27、asma a milky appearance.,Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT). This enzyme is present on the surface of HDL and is stimulated by the HDL component apoA-I. Cholesteryl esters accumulate within nascent HDLs, converting them to mature HDLs.,载脂蛋白在肝细胞内质网合成，在内质网组装成脂蛋白颗粒，在高尔基体
28、加工，包装成分泌小泡，分泌到肝细胞外。,脂蛋白颗粒的胞吞和降解,LDL受体的结构,SREBP activation. Sterol regulatory element-binding proteins (SREBPs, shown in green) are embedded in the ER when first synthesized, in a complex with the protein SREBP cleavage-activating protein (SCAP, red). (N and C represent the amino and carboxyl termini
29、 of the proteins.) When bound to SCAP, SREBPs are inactive. When sterol levels decline, the complex migrates to the Golgi complex, and SREBP is cleaved by two different proteases in succession. The liberated amino-terminal domain of SREBP migrates to the nucleus, where it activates transcription of
30、sterol-regulated genes.,Regulation of cholesterol formation balances synthesis with dietary uptake. Glucagon promotes phosphorylation (inactivation) of HMG-CoA reductase; insulin promotes dephosphorylation (activation). X represents unidentified metabolites of cholesterol that stimulate proteolysis of HMG-CoA reductase.,动脉斑的照片,胆酸和胆酸盐的合成,降低血清胆固醇的药物,7-脱氢酶的混合氧化酶活性,固醇类激素的合成,孕酮,孕烷醇酮,睾酮,醛固酮,雌二醇,一种兴奋剂,基本要求 1.掌握饱和脂肪酸的合成途径及调控。（重点） 2.熟悉不饱和脂肪酸的合成途径及调控。 3.熟悉磷脂、鞘脂类和甾醇的合成途径及调控。,
