生物化学第12章脂质和细胞膜

1、Berg Tymoczko Stryer Biochemistry Sixth EditionChapter 12:Lipids and Cell Membranes脂质和细胞膜脂质和细胞膜 The surface of a soap bubble is a bilayer formed by detergent (去垢剂) molecules. The polar heads (red) pack together, leaving the hydrophobic groups (green) in contact with air on the inside and outside of

2、the bubble. IntroductionMany Common Features Underlie the Diversityof Biological MembranesMembranes are as diverse in structure as they are in function. However, they do have in common a number of important attributes:1. Membranes are sheetlike structures, only two molecules thick, that form dosed b

3、oundaries between different compartments. The thickness of most membranes is between 60 (6 nm) and 100 (10 nm).2. Membranes consist mainly of lipids and proteins. The mass ratio of lipids to proteins ranges from 1:4 to 4:1. Membranes also contain carbohydrates that are linked to lipids and proteins.

4、3. Membrane lipids are small molecules that have both hydrophilic (亲水的) and hydrophobic (疏水的) moieties. These lipids spontaneously form closed bimolecular sheets in aqueous media. These lipid bilayers are barriers to the flow of polar molecules.4. Specific proteins mediate distinctive functions of m

5、embranes. Proteins serve as pumps, channels, receptors, energy transducers, and enzymes. Membrane proteins are embedded in lipid bilayers , which create suitable enviroments for their action.5. Membranes are noncovalent assemblies. The constituent protein and lipid molecules are held together by man

6、y noncovalent interactions, which act cooperatively,6. Membranes are asymmetric. The two faces of biological membranes always differ from each other.7. Membranes are fluid structures. Lipid molecules diffuse rapidly in the plane of the membrane, as do proteins, unless they are anchored by specific i

7、nteractions. In contrast, lipid molecules and proteins do not readily rotate across the membrane. Membranes can be regarded as two-dimensional solutions of oriented proteins and lipids.8. Most cell membranes are electrically polarized, such that the inside is negative typically - 60 millivolts (mV).

8、 Membrane potential plays a key role in transport, energy conversion, and excitability.OUTLINES1.Fatty Acids Are Key Constituents of Lipids 2.There Are Three Common Types of Membrane Lipids 3.Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media 4.Proteins Carry Out Most Mem

9、brane Processes 5.Lipids and Many Membrane Proteins Diffuse Rapidly in the plane of the Membrane 6.Eukaryotic Cells Contain Compartments Bounded by Internal MembranesThe hydrophobic (疏水的) properties of lipids are essential to their ability to form membranes. Most lipids owe their hydrophobic propert

10、ies to one component, their fatty acids.1.Fatty Acids Are Key Constituents of Lipids 1. Fatty Acids Are Key Constituents of LipidsFigure 12.2 Structures of two fatty acids. Palmitate is a 16-carbon, saturated fatty acid, and oleate is an l8-carbon fatty acid with a single cis double bond.棕榈酸油酸Fatty

11、acids are long hydrocarbon chains of various lengths and degrees of unsaturation terminated with carboxylic acid groups.Fatty Acid Names Are Based on Their Parent HydrocarbonsThe systematic name for a fatty acid is derived from the name of its parent hydrocarbon by the substitution of oic for the fi

12、nal e.Octadecane Octadecanoic acidThe notation 18:0 denotes a C18 fatty acid with no doublebonds, whereas 18:2 signifies that there are two double bonds.棕榈酸 (16:0)油酸 (18:1)HexadecaneHexadecanoic acidcis-D9-Octadecenecis-D9-Octadecenoic acid1. Fatty Acids Are Key Constituents of LipidsNomenclature (命

13、名命名)Fatty acid carbon atoms are numbered starting at the carboxyl terminus. Carbon atoms 2 and 3 are often referred to as a and b, respectively. The methyl carbon atom at the distal end of the chain is called the w-carbon atom.Fatty Acids Vary in Chain Length and Degree of Unsaturation1. Fatty Acids

14、 Are Key Constituents of Lipids月桂酸豆蔻酸棕榈酸硬脂酸廿烷酸山嵛酸木蜡酸棕榈油酸油酸亚油酸亚麻酸花生四烯酸OUTLINES1.Fatty Acids Are Key Constituents of Lipids 2.There Are Three Common Types of Membrane Lipids 3.Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media 4.Proteins Carry Out Most Membrane Processes 5.

15、Lipids and Many Membrane Proteins Diffuse Rapidly in the plane of the Membrane 6.Eukaryotic Cells Contain Compartments Bounded by Internal Membranes1. Phospholipids (磷脂磷脂)2. Glycolipids (糖脂糖脂)3. Cholesterol (胆固醇胆固醇)2. There Are Three Common Types of Membrane LipidsBy definition, lipids are water-ins

16、oluble biomolecules that are highly soluble in organic solvents such as chloroform. Lipids have a variety of biological roles: they serve as fuel molecules, highly concentrated energy stores, signal molecules and messengers in signal-transduction pathways, and components of membranes.Phospholipids A

17、re the Major Class of Membrane Lipids1. A phosphate2. One or more fatty acids3. A platform to which the fatty acids are attached4. An alcohol attached to the phosphatePhospholipids are abundant in all biological membranes. A phospholipidmolecule is constructed from four components:Figure 12.3 Schema

18、tic structure of a phospholipid.sphingosine The platform on which phospholipids are built may be glycerol (甘油), a three carbon alcohol, or sphingosine (鞘氨醇), a more complex alcohol. 甘油鞘氨醇Phospholipids Are the Major Class of Membrane LipidsPhosphoglyceride (磷酸甘油酯) Sphingomyelin (鞘磷脂)The common alcoho

19、l moieties of phosphoglycerides are the amino acid serine, ethanolamine (乙醇胺), choline (胆碱), glycerol, and inositol (肌醇).2. There Are Three Common Types of Membrane LipidsOnly smaIl amounts of phosphatidate (磷脂酸) are present in membranes. However, the molecule is a key intermediate in the biosynthes

20、is of the other phosphoglycerides (甘油磷脂). 乙醇胺胆碱肌醇甘油丝氨酸Figure 12.5 Some commonphosphoglycerides found in membranes.Phospholipids2. There Are Three Common Types of Membrane Lipids心磷脂磷脂酰丝氨酸磷脂酰胆碱磷脂酰肌醇磷脂酰乙醇胺The backbone in sphingomyelin is sphingosine (鞘氨醇), an amino alcohol that contains a long, unsatur

21、ated hydrocarbon chain. In sphingomyelin (鞘磷脂), the amino group of the sphingosine backbone is linked to a fatty acid by an amide bond. In addition, the primary hydroxyl group of sphingosine is esterified to phosphorylcholine (磷酰胆碱).sphingosine鞘氨醇Sphingomyelin (鞘磷脂)Membrane Lipids Can Include Carboh

22、ydrate MoietiesGlycolipids (糖脂), as their name implies, are sugar-containing lipids.脑苷脂Glycolipids cluster on the cell membrane, and extremely important in cell biochemical signaling.Cholesterol (胆固醇胆固醇) is a steroid (甾体甾体), built from four linked hydrocarbon rings.CholesterolIn membranes, the orien

23、tation of the molecule is parallel to the fatty acid chains of the phospholipids, and the hydroxyl group interacts with the nearby phospholipid head groups. Cholesterol is absent from prokaryotes but is found to varying degrees in virtually all animal membranes.Archaeal Membranes Are Built from Ethe

24、r Lipids with Branched Chains2. There Are Three Common Types of Membrane LipidsFigure 12.7 An archaeon and its environment. Archaea can thrive in habitats as harsh as a volcanic vent. Here, the archaea form an orange mat surrounded by yellow sulfurous deposits. Functional Genome of ThermophilesHyper

25、thermophiliesThermophiliesPsychrophiliesq DNA polymerase from Thermus aquaticus (Taq)；q Industrial processq -High tempratureq -High presureq -High concentration of organic solventq -Extreme pH. Archaeal (古菌的古菌的) Membranes Are Built from Ether Lipids with Branched ChainsArchaeal Membranes Are Built f

26、rom Ether Lipids with Branched ChainsThese branched, salurated hydrocarbons are more resistant to oxidation, which may help these organisms to with stand the extreme conditions, such as high temperature, low pH, or high salt concentration.A Membrane Lipid Is an Amphipathic MoleculeFigure 12.8 Repres

27、entations of membrane lipids. All the membrane lipids are amphipathic molecules (双亲性分子). They contains both a hydrophilic (亲水的) and a hydrophobic (疏水的) moiety.The two hydrophobic fatty acid chains are approximately parallel to each other, whereas the hydrophilic phosphorylcholine moiety points in th

28、e opposite direction.OUTLINES1.Fatty Acids Are Key Constituents of Lipids 2.There Are Three Common Types of Membrane Lipids 3.Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media 4.Proteins Carry Out Most Membrane Processes 5.Lipids and Many Membrane Proteins Diffuse Rapidl

29、y in the plane of the Membrane 6.Eukaryotic Cells Contain Compartments Bounded by Internal MembranesWhat properties enable phospholipids to form membranes? Membrane formation is a consequence of the amphipathic nature of the molecules. Their polar head groups favor contact with water, whereas their

30、hydrocarbon tails interact with one another in preference to water. Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media Figure 12.9 Diagram of a section of a micelle.3. Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous MediaHow can molecules with the

31、se preferences arrange themselves in aqueous solutions? One way is to form a globular structure called a micelle (胶束).The polar head groups form the outside surface of the micelle, which is surrounded by water, and the hydrocarbon tails are sequestered inside, interacting with one anotherFigure 12.1

32、0 Diagram of a section of a bilayer membrane.The favored structure for most phospholipids and glycolipids in aqueous media is a bimolecular sheet rather than a micelle.Alternatively, the strongly opposed preferences of the hydrophilic and hydrophobic moieties of membrane lipids can be satisfied by f

33、orming a lipid bilayer, composed of two lipid sheets3. Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous MediaFigure 12.11 Space-fitting model of a section of phospholipid bilayer membrane. (A) An idealized view showing regular structures. (B) A more realistic view of a fluid

34、bilayer showing more irregular structures of the fatty acid chains.3. Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous MediaPhospholipids and related molecules are important membrane constituents because they readily form extensive bimolecular sheets.Lipid bilayers form spont

35、aneously (自发的) by a self-assembly (自主装) process. In other words, the structure of a bimolecular sheet is inherent in the structure of the constituent lipid molecules. The driving force for the formation of lipid bilayers:Hydrophobic interactions (The most important force)van der Waals attractive for

36、ces between the tailselectrostatic and hydrogen-bonding attractions between the polar head groups and water moleculesThese hydrophobic interactions have three significant biological consequences: lipid bilayers have an inherent tendency to be extensive; lipid bilayers will tend to close on themselve

37、s so that there are no edges with exposed hydrocarbon chains, and so they form compartments;lipid bilayers are self-sealing because a hole in a bilayer is energetically unfavorable.Lipid vesicles, or Liposome, Can Be Formed from PhospholipidsFigure 12.12 Liposome. Liposomes are formed by suspending

38、a suitable lipid, such as phosphatidylcholine, in an aqueous medium. and then sonicating to give a dispersion of closed vesicles that are quite uniform in size.The propensity of phospholipids to form membranes has been used to create an important experimental and clinical tool. Lipid vesicles, or li

39、posomes, are aqueous compartments enclosed by a lipid bilayerFigure 12.13 Preparation of glycine-containing liposomes. Liposomes containing glycine are formed by the sonication of phospholipids in the presence of glycine. Free glycine is removed by gel filtration.3. Phospholipids and Glycolipids Rea

40、dily Form Bimolecular Sheets in Aqueous MediaIons or molecules can be trapped in the aqueous compartments of lipid vesicles by forming the vesicles in the presence of these substances. 3. Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous MediaFigure 12.14 Experimental arrangem

41、ent for the study of a planar bilayer membrane (平面双层膜平面双层膜). A bilayer membrane is formed across a l-mm hole in a septum that separates two aqueous compartments. This arrangement permits measurements of the permeability and electrical conductance of lipid bilayers. The permeability of membrane (透过性)

42、 to ions can be determined by measuring the current across the membrane as a function of the applied voltage. Lipid Bilayers Are Highly Impermeable to Ions and Most Polar MoleculesFigure 12.15 Permeability coefficients (P) of ions and molecules in a lipid bilayer. The ability of molecules to cross a

43、 lipid bilayer spans a wide range of values. The permeability of small molecules is correlatedwith their solubility in a nonpolar (非极性的) solvent relative to their solubility in waterOUTLINES1.Fatty Acids Are Key Constituents of Lipids 2.There Are Three Common Types of Membrane Lipids 3.Phospholipids

44、 and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media 4.Proteins Carry Out Most Membrane Processes 5.Lipids and Many Membrane Proteins Diffuse Rapidly in the plane of the Membrane 6.Eukaryotic Cells Contain Compartments Bounded by Internal MembranesFigure 12.16 SDS-acrylamide gel pattern

45、s of membrane proteins. (A) The plasma membrane of erythrocytes. (B) The photoreceptor membranes of retinal rod cells. (C) The sarcoplasmic reticulum membrane of muscle cells.4. Proteins Carry Out Most Membrane ProcessesMembrane lipids form a permeability barrier and thereby establish compartments,

46、whereas specific proteins mediate nearly all other membrane functions .Myelin (髓鞘脂), a membrane that serves as an electrical insulator (绝缘体) around certain nerve fibers, has a low content of protein (18%).The protein content of the plasma membranes is typically 50%. Energy-transduction membranes hav

47、e the highest content of protein, typically 75%.Proteins Associate with the Lipid Bilayer in a Variety of Ways4. Proteins Carry Out Most Membrane ProcessesFigure 12.17 Integral and peripheral membrane proteins. Integral membrane proteins (a. b. and c) interact extensively with the hydrocarbon region

48、 of the bilayer. Most known integral membrane proteins traverse the lipid bilayer. Peripheral membrane proteins (d and e) bind to the surfaces of integral proteins. Some peripheral membrane proteins interact with the polar head groups of the lipids (not shown).Membrane proteins can be classified as

49、being either peripheral (外围的) or integral （整合的） on the basis of this difference in dissociability.Integral membrane proteins (a, b, c) interact extensively with the hydrocarbon chains of membrane lipids, and they can be released only by agents that compete for these nonpolar interactions. In fact, m

50、ost integral membrane proteins span the lipid bilayer.Peripheral membrane proteins (d, e) are bound to membranes primarily by electrostatic and hydrogen bond interactions with the head groups of lipids. These polar interactions can be disrupted by adding salts or by changing the pH.Figure 12.18 Stru

51、cture of bacteriorhodopsin (菌视紫红质). Notice that bacteriorhodopsin consists largely of membrane-spanning a helices (represented by yellow cylinders). (A) View through the membrane bilayer. The interior of the membrane is green and the head groups are red. (B) View from the cytoplasmic side of the mem

52、brane.1. Proteins Can Span the Membrane with Alpha Helices.Proteins Associate with the Lipid Bilayer in a Variety of WaysMembrane-spanning a helices are the most common structural motif in membrane proteins.Most of the amino acids in these membrane spanning a helices are nonpolar and only a very few

53、 are charged. This distribution of nonpolar amino acids is sensible because these residues are either in contact with the hydrocarbon core of the membrane or with one another.Figure 12.19 Amino acid sequence of bacteriorhodopsin. The seven helical regions are highlighted in yellow and the charged re

54、sidues in red. Proteins Associate with the Lipid Bilayer in a Variety of WaysFigure 12.20 Structure of bacterial porin (from Rhodopseudomonas blastica). This membrane protein is built entirely of b strands. (A) Side view. (B) View from the periplasmic space. Only one monomer of the trimeric protein

55、is shown.2. A Channel Protein Can Be Formed from Beta Strands.Proteins Associate with the Lipid Bilayer in a Variety of WaysPorin (孔蛋白), a protein from the outer membranes of bacteria such as E. coli (大肠杆菌) and Rhodobacter caprulatus (荚膜红细菌), represents a class of membrane proteins with a completely

56、 different type of structure.Figure 12.21 Amino acid sequence of a porin.Proteins Associate with the Lipid Bilayer in a Variety of WaysThe outside surface of porin is appropriately nonpolar while the inside of the channel is quite hydrophilic. The arrangement of nonpolar and polar surfaces is accomp

57、lished by the alternation of hydrophobic and hydrophilic amino acids along each b strandThe structure of the endoplasmic reticulum membrane-bound enzyme prostaglandin (前列腺素) H2 synthase-1 reveals a rather different role for a helices in protein-membrane associations. This enzyme catalyzes the conver

58、sion of arachidonic acid （花生四烯酸） into prostaglandin H2 in two steps: (1) a cyclooxygenase (环加氧酶) reaction and (2) a peroxidase (过氧化物酶) reaction. Proteins Associate with the Lipid Bilayer in a Variety of Ways3. Embedding Part of a Protein in a Membrane Can Link the Protein to the Membrane Surface.Fig

59、ure 12.23 Attachment of prostaglandin H2 synthase-1 to the membrane. Notice that prostaglandin H2 synthase-l is held in the membrane by a set of a helices (orange) coated with hydrophobic side chains. One monomer of the dimeric enzyme is shown.3. Embedding Part of a Protein in a Membrane Can Link th

60、e Protein to the Membrane Surface.Proteins Associate with the Lipid Bilayer in a Variety of WaysIt is classified as an integral membrane protein, although it is not a membrane-spanning protein. Figure 12.23 Attachment of prostaglandin H2 synthase-1 to the membrane. Notice that prostaglandin H2 synth