第六章脂类代谢The sixth chapter is lipid metabolism文档格式.docx

1、3. master of palmitic acid synthesis parts, raw materials, pathways and key enzymes; familiar with fatty acid chain length and saturation to understand the regulation of fatty acid metabolism.4. familiar with the biosynthesis of lecithin and brain phospholipids.5. familiar with the site, raw materia

2、l, process and transformation of cholesterol synthesis.Introduction: lipid is an important nutrient of the human body, divided into two categories: fat and lipid. The main function of fat is energy storage and energy supply. Lipids, including phospholipids, glycolipids, cholesterol and their esters,

3、 are important components of biological membranes, involved in cell recognition and information transmission, and are precursors of a variety of biologically active substances. There are two sources of fatty acids in the body: first, the body itself is synthesized, stored in fat tissue as fat, and m

4、obilized from fat as needed. Saturated fatty acids and monounsaturated fatty acids are mainly synthesized by the organism itself. Another source of dietary fat supply, especially some polyunsaturated fatty acids, the animal body itself can not be synthesized, need to be extracted from vegetable oil,

5、 called essential fatty acids. This chapter focuses on the decomposition and anabolism of fats.Section 1 IntroductionLipidsFat （fat）, also known as triglyceride （triglyceride, TG）. Fat cells are the major reservoir of mammalian fat. Glycogen can be in a short time （about 1H） is used to provide energ

6、y for muscle contraction, but sustained, intense work, such as the marathon race, migratory birds lasting flight and locust migration, the energy source depends on the metabolism of TG. 1g oxidation release 37.6 kJ, more than 2 times more than the same amount of sugar or protein.Most natural fatty a

7、cids are even numbers C, 16C or 18C are common; linoleic acid, linolenic acid and peanut four acids are the essential fatty acids in unsaturated fatty acids.Phospholipids are divided into glycerol, lecithin and sphingomyelin according to their chemical structure.Glycerophospholipids are the most con

8、tent of lipids in biological membranes, the core structure is -3- C1 and glycerol phosphate, C2 hydroxyl groups are 2 acyl substituted long chain （hydrophobic tail）, phosphate and hydroxyl C3 with various substituents to form the polar head. Including phosphatidylcholine （lecithin, PC）, phosphatidyl

9、ethanolamine （PE, PE）, phosphatidylserine （PS）, phosphatidylglycerol and phosphatidylglycerol （two cardiolipin） and phosphatidylinositol （PI） six classes, each class with different fatty acid composition and several kinds of the red blood cells, there are more than 100 kinds of different phospholipi

10、ds. Sphingomyelin and cerebrosides and gangliosides of sphingolipids, higher content in nerve tissue and brain. Consisting of a molecule of fatty acid, a molecule of sphingosine or derivatives thereof, and a polar head group.Sterol is a derivative of cyclopentane, phenanthrene and phenanthrene. Chol

11、esterol （cholesterol, Ch） and cholesterol esters are important components of plasma proteins and extracellular membrane. Cholesterol regulates the fluidity of biological membranes and is also the precursor to the synthesis of biologically active substances such as bile acids, steroids, and vitamin D

12、.Two. BiofilmThe outer membrane of cells and the inner membrane system of organelles are collectively called biofilms. Its function is to maintain the intracellular environment is relatively stable barrier, but also for substance exchange, cell identification, information transmission sites, the int

13、ernal membrane system enzymes to regional distribution, to ensure that a variety of biochemical reactions in an orderly manner. The basic structure of the membrane is the lipid bilayer, and is explained by the fluid mosaic model.Three. Enzymatic hydrolysis of lipids1. lipase is found widely in anima

14、ls, plants and microorganisms. In humans, the digestion of fat is mainly in the small intestine, catalyzed by pancreatic lipase, which assists the gradual hydrolysis of fats to produce fatty acids and glycerol.2. phospholipase has a variety of ester bonds that act on different parts of the phospholi

15、pid molecule. The 1 and 2 ester bonds are called phospholipase A1 and A2,Formation of lysophosphatidic acid and free fatty acid. The enzyme acting on the 3 position, called phospholipase C, acts as an enzyme that acts as an alternative to the ester bond between the phosphate substituents and is call

16、ed phospholipase D. The enzyme acting on the 1 - point ester bond is called phospholipase B1.3. cholesterol esterase hydrolyze cholesterol esters to produce cholesterol and fatty acids.4. small intestine can absorb the hydrolysis products of lipids. Bile salts help emulsify and form apoprotein, a fo

17、rm of apo that is absorbed by intestinal mucosal cells into the blood circulation. Thus, CM （chylomicron） is a lipoprotein that transfers exogenous lipids （mainly TG）.Catabolism of second sections of fatThe fat in the food through the digestive lipase was gradually degraded into glycerol and free fa

18、tty acid （FFA）, and stored in the fat cells in the fat fat mobilization in the degradation of fat mobilization, three triacylglycerol lipase activity is low, the rate limiting enzyme of fat mobilization. Lipolysis is the first step in an organisms use of fat as an energy source.I. oxidation of glyce

19、rolThe glycerol produced by fat mobilization is mainly produced by the action of glycerol kinase in liver cells, which is produced by 3-, followed by the pathway of glucose metabolism, or by gluconeogenesis. Adipose tissue and skeletal muscle tissues can not make good use of glycerol because of thei

20、r low activity of glycerol kinase.Two, the oxidation of fatty acidsFatty acids, insoluble in water, bind together with albumin in the blood （10:1）, transport the tissues of the body, oxidize and break down in the tissues of the mitochondria, release large amounts of energy, and activate the liver an

21、d muscles most actively. In 1904, Knoop labeled with benzene, trace the fatty acids in the transformation process of animal body, found that when the odd carbon fatty acid derivatives were degraded when detected in urine is hippuric acid, if even carbon, urine is phenaceturic acid. Obviously the deg

22、radation of fatty acyl chain occurs in the beta carbon atom, i.e. each from the fatty acid chain cutting unit under a second. After the scientific experiments prove that beta oxidation theory is correct, the second cut unit is acetyl CoA, fatty acid into mitochondria before being activated.（I） activ

23、ation of fatty acidsIn cytosol, FFA is activated by esterification with CoA, which catalyzes the synthesis of the acyl CoA synthetase, involving ATP and Mg2+. The resulting PPi is immediately hydrolyzed by the phosphatase, which prevents the reverse reaction, so the activation of the 1 molecule FFA

24、actually consumes 2 high-energy phosphate bonds.RCOOH+ATP+CoASH - RCOSCoA+AMP+PPi（two） acyl CoA enters mitochondriaThe oxidation of fatty acids is carried out in mitochondria, whereas acyl CoA is not free to enter the stroma through the mitochondrial membrane and is required to transport carnitine v

25、ia mitochondria via carnitine transport in the mitochondrial membrane. The acyl carnitine acyltransferase CoA and II （isozymes） catalyze the transport of acyl transporters and release of carnitine. Enzyme I is the dominant rate limiting enzyme in FFA oxidation decomposition.（three） beta oxidation of

26、 acyl CoAThe oxidation of acetyl CoA to acetyl CoA involves four basic reactions: the first oxidation reaction, the hydration reaction, the second oxidation reaction and the sulfur hydrolysis reaction.The first step is catalyzed by acyl CoA dehydrogenase dehydrogenation of anti - Delta 2- enoyl CoA

27、and FADH2.The second step by anti - Delta 2- enoyl CoA hydratase catalyzing water to generate L- （+） - beta hydroxy acyl CoA.The third step, catalyzed by L- （+） - beta hydroxy CoA dehydrogenase, produces beta keto acyl CoA and NADH+H+.The fourth step involves the cleavage of alpha - to beta -C betwe

28、en the substrate and the CoA, and CoASH participates in the formation of 1 acetyl CoA and less than 2 C of lipid acyl. Then another round of beta oxidation, so cyclic reactions.（four） energy calculation of fatty acid oxidation1 molecules of palmitic acid （16C） after 7 beta oxidation can generate 8 a

29、cetyl CoA, 7 NADH+H+, 7 FADH2. Each acetyl CoA enters the TCA cycle, generating 3 NADH+H+, 1 FADH2, 1 GTP, and releasing 2 molecules CO2.The total reaction equation is: CoA+23 O2+131Pi+131ADP, CoASH+16 CO2+123H2O+131ATP hexadecanoylThe number of ATP net generation: 12 * * * =129 83 7 2 7-2. （fatty a

30、cid activation consumes 2 high-energy phosphate bonds, which consume 2 ATP）When fat is used as energy, the organism also gets a lot of water. The camels hump is a storehouse of stored fat that provides both energy and water.（five） other pathways for the oxidation of fatty acids1. oxidation of an odd

31、 numbered carbon atom fatty acidThe body contains a very small amount of odd numbered carbon fatty acids, while many plants, marine organisms, petroleum yeasts, etc. contain a certain amount of odd numbered carbon fatty acids. In addition to producing acetyl CoA, the beta oxidation also generates a 1 molecule, propyl CoA, which produces succinate CoA via beta carboxylase and isomerase and is thoroughly oxidized by TCA pathway.2. oxidation of unsaturated fatty acidsThe body fat acid about