脂肪酸的代谢3.ppt
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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
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