H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 62
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A phosphogyceride is5.1 • Biomembranes: Lipid Composition and Structural Organizationin plasmalogens or the subtle differences in their threedimensional structure compared with that of other phosphoglycerides may have as-yet unrecognized physiologicsignificance.A second class of membrane lipid is the sphingolipids.All of these compounds are derived from sphingosine, anamino alcohol with a long hydrocarbon chain, and contain along-chain fatty acid attached to the sphingosine aminogroup. In sphingomyelin, the most abundant sphingolipid,phosphocholine is attached to the terminal hydroxyl groupof sphingosine (Figure 5-5b).
Thus sphingomyelin is a phospholipid, and its overall structure is quite similar to that ofphosphatidylcholine. Other sphingolipids are amphipathicglycolipids whose polar head groups are sugars. Glucosylcerebroside, the simplest glycosphingolipid, contains a singleglucose unit attached to sphingosine. In the complex glycosphingolipids called gangliosides, one or two branchedsugar chains containing sialic acid groups are attached toclassified according to the nature of its head group. In phosphatidylcholines, the most abundant phospholipids in theplasma membrane, the head group consists of choline, a positively charged alcohol, esterified to the negatively chargedphosphate. In other phosphoglycerides, an OH-containingmolecule such as ethanolamine, serine, and the sugar derivative inositol is linked to the phosphate group.
The negatively charged phosphate group and the positively chargedgroups or the hydroxyl groups on the head group interactstrongly with water.The plasmalogens are a group of phosphoglycerides thatcontain one fatty acyl chain, attached to glycerol by an esterlinkage, and one long hydrocarbon chain, attached to glycerol by an ether linkage (COOOC). These molecules constitute about 20 percent of the total phosphoglyceridecontent in humans. Their abundance varies among tissuesand species but is especially high in human brain and hearttissue. The additional chemical stability of the ether linkageH132OOOHN+OHydrophobic tailPEHOCH3PN+O−OHOH6OH4521NHPSO−OHHOOO3OCH3PN+O−PCHN+OOHCH3CH3O(b) Sphingolipids FIGURE 5-5 Three classes ofHead group(a) PhosphoglyceridesOOOHOHPICH3CH3SMOOHOOOHHOOH(c) CholesterolOH151GlcCermembrane lipids.
(a) Mostphosphoglycerides are derivatives ofglycerol 3-phosphate (red) containing twoesterified fatty acyl chains, constitutingthe hydrophobic “tail” and a polar “headgroup” esterified to the phosphate. Thefatty acids can vary in length and besaturated (no double bonds) or unsaturated(one, two, or three double bonds). Inphosphatidylcholine (PC), the head groupis choline. Also shown are the moleculesattached to the phosphate group in threeother common phosphoglycerides:phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol(PI). (b) Sphingolipids are derivatives ofsphingosine (red), an amino alcohol witha long hydrocarbon chain.
Various fattyacyl chains are connected to sphingosineby an amide bond. The sphingomyelins(SM), which contain a phosphocholinehead group, are phospholipids. Othersphingolipids are glycolipids in whicha single sugar residue or branchedoligosaccharide is attached to thesphingosine backbone. For instance, thesimple glycolipid glucosylcerebroside(GlcCer) has a glucose head group.(c) Like other membrane lipids, the steroidcholesterol is amphipathic. Its singlehydroxyl group is equivalent to the polarhead group in other lipids; the conjugatedring and short hydrocarbon chain form thehydrophobic tail.
[See H. Sprong et al., 2001,Nature Rev. Mol. Cell Biol. 2:504.]152CHAPTER 5 • Biomembranes and Cell Architecturesphingosine. Glycolipids constitute 2–10 percent of the totallipid in plasma membranes; they are most abundant in nervous tissue.Cholesterol and its derivatives constitute the third important class of membrane lipids, the steroids. The basicstructure of steroids is a four-ring hydrocarbon.
Cholesterol,the major steroidal constituent of animal tissues, has a hydroxyl substituent on one ring (Figure 5-5c). Although cholesterol is almost entirely hydrocarbon in composition, it isamphipathic because its hydroxyl group can interact withwater. Cholesterol is especially abundant in the plasma membranes of mammalian cells but is absent from most prokaryotic cells. As much as 30–50 percent of the lipids in plantplasma membranes consist of certain steroids unique toplants.At neutral pH, some phosphoglycerides (e.g., phosphatidylcholine and phosphatidylethanolamine) carry no netelectric charge, whereas others (e.g., phosphatidylinositoland phosphatidylserine) carry a single net negative charge.Nonetheless, the polar head groups in all phospholipids canpack together into the characteristic bilayer structure.
Sphingomyelins are similar in shape to phosphoglycerides and canform mixed bilayers with them. Cholesterol and othersteroids are too hydrophobic to form a bilayer structure unless they are mixed with phospholipids.Most Lipids and Many Proteins Are LaterallyMobile in BiomembranesIn the two-dimensional plane of a bilayer, thermal motion permits lipid molecules to rotate freely around their long axes andto diffuse laterally within each leaflet.
Because such movements are lateral or rotational, the fatty acyl chains remain inthe hydrophobic interior of the bilayer. In both natural and ar-(a)Fluorescent reagentMembrane proteinCellBleached areaLabelBleach withlaserFluorescencerecovery123Fluorescence intensity (arb. units)(b)Fluorescence before bleaching300050%immobile200050%mobile1000Bleach50100Time (s)150▲ EXPERIMENTAL FIGURE 5-6 Fluorescence recoveryafter photobleaching (FRAP) experiments can quantify thelateral movement of proteins and lipids within the plasmamembrane. (a) Experimental protocol. Step 1 : Cells are firstlabeled with a fluorescent reagent that binds uniformly to aspecific membrane lipid or protein.
Step 2 : A laser light is thenfocused on a small area of the surface, irreversibly bleaching thebound reagent and thus reducing the fluorescence in theilluminated area. Step 3 : In time, the fluorescence of thebleached patch increases as unbleached fluorescent surfacemolecules diffuse into it and bleached ones diffuse outward. Theextent of recovery of fluorescence in the bleached patch isproportional to the fraction of labeled molecules that are mobilein the membrane.
(b) Results of FRAP experiment with humanhepatoma cells treated with a fluorescent antibody specific forthe asialoglycoprotein receptor protein. The finding that 50percent of the fluorescence returned to the bleached areaindicates that 50 percent of the receptor molecules in theilluminated membrane patch were mobile and 50 percent wereimmobile. Because the rate of fluorescence recovery isproportional to the rate at which labeled molecules move into thebleached region, the diffusion coefficient of a protein or lipid inthe membrane can be calculated from such data. [See Y.
I. Henis etal., 1990, J. Cell Biol. 111:1409.]5.1 • Biomembranes: Lipid Composition and Structural Organizationtificial membranes, a typical lipid molecule exchanges placeswith its neighbors in a leaflet about 107 times per second anddiffuses several micrometers per second at 37 C. These diffusion rates indicate that the viscosity of the bilayer is 100 timesas great as that of water—about the same as the viscosity ofolive oil. Even though lipids diffuse more slowly in the bilayerthan in an aqueous solvent, a membrane lipid could diffuse thelength of a typical bacterial cell (1 m) in only 1 second andthe length of an animal cell in about 20 seconds.The lateral movements of specific plasma-membrane proteins and lipids can be quantified by a technique called fluorescence recovery after photobleaching (FRAP). With thismethod, described in Figure 5-6, the rate at which membranelipid or protein molecules move—the diffusion coefficient—can be determined, as well as the proportion of the moleculesthat are laterally mobile.The results of FRAP studies with fluorescence-labeledphospholipids have shown that, in fibroblast plasma membranes, all the phospholipids are freely mobile over distancesof about 0.5 m, but most cannot diffuse over much longerdistances.
These findings suggest that protein-rich regions ofthe plasma membrane, about 1 m in diameter, separatelipid-rich regions containing the bulk of the membranephospholipid. Phospholipids are free to diffuse within sucha region but not from one lipid-rich region to an adjacentone. Furthermore, the rate of lateral diffusion of lipids in theplasma membrane is nearly an order of magnitude slowerthan in pure phospholipid bilayers: diffusion constants of108 cm2/s and 107 cm2/s are characteristic of the plasmamembrane and a lipid bilayer, respectively.
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