3 Биологические мембраны. Обмен веществом (1160072), страница 3
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Membrane lipids are amphipathic; the orientation oftheir hydrophobic and hydrophilic regions directs their packing intoChapter 9 Lipidsmembrane bilayers. Three general types of membrane lipids will bedescribed: glycerophospholipids, in which the hydrophobic regions arecomposed of two fatty acids joined to glycerol; sphingolipids, in which asingle fatty acid is joined to a fatty amine, sphingosine; and sterols,compounds characterized by a rigid system of four fused hydrocarbonrings. The hydrophilic moieties in these amphipathic compounds maybe as simple as a single —OH group at one end of the sterol ring system, or they may be more complex.
Glycerophospholipids and sphingolipids contain polar or charged alcohols at their polar ends; some alsocontain phosphate groups (Fig. 9-6). Within these three classes ofmembrane lipids, enormous diversity results from various combinations of fatty acid "tails" and polar "heads." We describe here a representative sample of the types of membrane lipids found in living organisms.
The arrangement of these lipids in membranes, and theirstructural and functional roles therein, are considered in the nextchapter.247Figure 9-6 The principal classes of storage andmembrane lipids. All of the classes shown herehave either glycerol or sphingosine as the backbone. A third class of membrane lipids, the sterols,is described later (see Fig. 9-13).Storagelipids(neutral)Membrane lipids (polar)GlycolipidsPhospholipids7GlycerophospholipidsTriacylglycerolsFatty acid-j Fatty acidgFatty acid3OFatty acidGlycerophospholipids Are Derivatives of Phosphatidic AcidMembranes contain several classes of lipids in which two fatty acidsare ester-linked to glycerol at C-l and C-2, and a highly polar orcharged (and therefore hydrophilic) head group is attached to C-3 (Fig.9-6).
The most abundant of these polar lipids in most membranes arethe glycerophospholipids, sometimes called phosphoglycerides (Fig.9-7). In glycerophospholipids, a polar alcohol is joined to C-3 of glycerol through a phosphodiester bond. All glycerophospholipids are derivatives of phosphatidic acid (Fig. 9-7) and are named for their polarhead groups (phosphatidylcholine and phosphatidylethanolamine, forexample). All have a negative charge on the phosphate group atpH 7.0. The head-group alcohol may also contribute one or morecharges at pH near 7.Fatty acidFatty acidSphiiycerolFatty acidSphingolipidsmm248Part II Structure and CatalysisOSaturated fattyacid (e.g., palmitic)Glycerophospholipid2(generalCH—O—structure)Unsaturatedfatty acid(e.g., oleic)3CH2—O—P—O—jOName of XHead-groupsubstituentFormula of XName ofglycerophospholipidPhosphatidic acidNet charge(at pH 7)-1EthanolaminePhosphatidylethanolamine0CholinePhosphatidylcholine0SerinePhosphatidylserineGlycerolPhosphatidylglycerolInositolPhosphatidylinositolPhosphatidylglycerolCardiolipin-1-1-1Figure 9-7 The common glycerophospholipidsare diacylglycerols linked to head-group alcoholsthrough a phosphodiester bond.
Phosphatidic acidis the parent compound, a phosphomonoester. Eachderivative is named for the head-group alcohol (X),with the prefix "phosphatidyl." In cardiolipin, twophosphatidic acids share a single glycerol.-2Chapter 9 Lipids249The fatty acids in glycerophospholipids can be any of a wide variety. They are different in different species, in different tissues of thesame species, and in different types of glycerophospholipids in thesame cell or tissue. In general, glycerophospholipids contain a saturated fatty acid at C-l and an unsaturated fatty acid at C-2, and thefatty acyl groups are commonly 16 or 18 carbons long—but there aremany exceptions.Some Phospholipids Have Ether-Linked Fatty AcidsSome animal tissues and some unicellular organisms are rich in etherlipids, in which one of the two acyl chains is attached to glycerol inether, rather than ester, linkage.
The ether-linked chain may be saturated, as in the alkyl ether lipids, or may contain a double bond between C-l and C-2, as in plasmalogens (Fig. 9-8). Vertebrate hearttissue is uniquely enriched in ether lipids; about half of the heart phospholipids are plasmalogens. The membranes of halophilic bacteria, ofciliated protists, and of certain invertebrates also contain high proportions of ether lipids. Their functional significance in these membranesis unknown; perhaps they confer resistance to phospholipases thatcleave ester-linked fatty acids from membrane lipids. At least oneether lipid, platelet-activating factor (Fig.
9-8), is an importanthormone. It is released from white blood cells called basophils andstimulates platelet aggregation and the release of serotonin fromplatelets. It exerts a variety of effects on liver, smooth muscle, heart,uterine, and lung tissues, and plays an important role in inflammationand the allergic response.ether linkageH HtCH2—O—CH2—CH2XCH2—O—C=C22CH-O-C34H 2CH-O-C-CH3CH2O0acetyl esterIO=P—O—CH2—CH2—N(CH3)3I0=P-O-CH2-CH2-N(CH3)3PlasmalogenOFigure 9—8 Plasmalogens and platelet-activatingfactor.
Plasmalogens have one ether-linked alkenylchain where most glycerophospholipids have anester-linked fatty acid (compare Fig. 9—7). Plateletactivating factor has a long ether-linked alkyl chainat C-l of glycerol, but C-2 is ester-linked to a verySphingolipids Are Derivatives of SphingosineSphingolipids, the second large class of membrane lipids, also have apolar head and two nonpolar tails, but unlike glycerophospholipidsthey contain no glycerol. Sphingolipids are composed of one molecule ofthe long-chain amino alcohol sphingosine (4-sphingenine) or one of itsderivatives, one molecule of a long-chain fatty acid, a polar head alcohol, and sometimes phosphoric acid in diester linkage at the polar headgroup (Fig. 9-9).Platelet-activating factorshort fatty acid (acetic acid), which makes the compound much more water-soluble than most glycerophospholipids and plasmalogens.
The head groupalcohol is choline in plasmalogens and plateletactivating factor.250Part II Structure and CatalysisSphingosineHO— 3 CH—CH==CH—(CH 2 )i 2 —CH 3Sphingolipid(generalstructure)Fatty acidO2Ceramide(when X = H)CH—N—C.HName of XFormula of X-HPhosphocholineGlucose—jName of sphingolipidCeramideSphingomyelinGlucosylcerebrosideNeutralglycolipidsDi-, tri-, ortetrasaccharideLactosylceramideComplexoligosaccharideGanglioside G M2Figure 9 - 9 Sphingolipids.
The first three carbonsat the polar end of sphingosine are analogous tothe three carbons of glycerol in glycerophospholipids. In ceramide, the parent compound forthis group, the amino group at C-2 bears a fattyacid in amide linkage. Individual sphingolipids differ in the polar head group (X) attached at C-l. Thefatty acid components of sphingolipids are usuallysaturated or monounsaturated, and contain 16, 18,22, or 24 carbon atoms. Gangliosides have verycomplex oligosaccharide head groups. These compounds are given identifying symbols (e.g., G M i,GM2) that indicate the structure of the head group.At least 15 different classes of gangliosides havebeen found in higher animals.
Standard symbols forsugars are used in this figure: Glc, D-glucose; Gal,D-galactose; GalNAc, iV-acetyl-D-galactosamine;NeuNAc, Af-acetylneuraminic acid (sialic acid).Carbons C-l, C-2, and C-3 of the sphingosine molecule bear functional groups (—OH, — NH2, —OH) that are structurally homologouswith the three hydroxyl groups of glycerol in glycerophospholipids.When a fatty acid is attached in amide linkage to the — NH2, the resulting compound is a ceramide (Fig. 9-9), which is structurally similar to a diacylglycerol. Ceramide is the fundamental structural unitcommon to all sphingolipids.There are three subclasses of sphingolipids, all derivatives of ceramide, but differing in their head groups: sphingomyelins, neutral (uncharged) glycolipids, and gangliosides (Fig.
9-9). Sphingomyelinscontain phosphocholine or phosphoethanolamine as their polar headgroup, and are therefore classified as phospholipids, together withglycerophospholipids. Indeed, sphingomyelins resemble phosphatidylcholines in their general properties and three-dimensional structure,and in having no net charge on their head groups (Fig. 9-10). Sphingomyelins are present in plasma membranes of animal cells; the myelinsheath which surrounds and insulates the axons of myelinated neurons is a good source of sphingomyelins, and gives them their name.Chapter 9 Lipids2510~0=P—OICH3 CH 2 OCH3-NCH3 CH2—OCH2CH3-N—CH20=CH3PhosphatidylcholineSphingomyelinFigure 9—10 The similarities in shape and in molecular structure of phosphatidylcholine (a glycerophospholipid) and sphingomyelin (a sphingolipid)Neutral glycolipids and gangliosides have one or more sugars intheir head group, connected directly to the —OH at C-l of the ceramidemoiety; they do not contain phosphate.
These sugar-containing sphingolipids are sometimes called glycosphingolipids. Neutral glycolipids contain one to six (sometimes more) sugar units, which may beD-glucose, D-galactose, or iV-acetyl-D-galactosamine (Fig. 9-9). Theseglycosphingolipids occur largely in the outer face of the plasma membrane. Cerebrosides have a single sugar linked to ceramide (Fig.9-9); those with galactose are characteristically found in the plasmamembranes of cells in neural tissue, and those with glucose, in theplasma membranes of cells in nonneural tissues.Gangliosides, the most complex sphingolipids (Fig. 9-9), containvery large polar heads made up of several sugar units. One or more ofthe terminal sugar units of gangliosides is iV-acetylneuraminic acid,also called sialic acid, which has a negative charge at pH 7.
Gangliosides make up about 6% of the membrane lipids in the gray matter ofthe human brain, and they are present in lesser amounts in the membranes of most nonneural animal tissues.are clear when their space-filling and structuralformulas are drawn as here.900OH OHA°x IICH20HH/^JJ\ CH—CH—HHHHN—C—CH 3OAf-Acetylneuraminic acid(sialic acid)252Part II Structure and CatalysisSphingolipids Are Sites of Biological RecognitionWhen the sphingolipids were discovered a century ago by the physician-chemist Johann Thudicum, their biological role seemed as enigmatic as the Sphinx, for which he named them. Sphingolipids are nowknown to be involved in various recognition events at the cell surface.For example, glycosphingolipids are the determinants of the humanblood groups A, B, and O (Fig.
9-11). The ganglioside GMI, whichdoubtless plays some role of value to the animal cell that contains it, isthe point of attachment of cholera toxin as it attacks an animal cell, acase of coevolution of a host cell and its pathogenic parasite. The membranes of the human nervous system contain at least 15 different gangliosides for which no function is yet known. However, it is clearlyimportant that the synthesis and breakdown of these compounds betightly regulated; derangements in the metabolism of cerebrosides andgangliosides underlie the devastating effects of several human geneticdiseases, including Tay-Sachs and Niemann-Pick diseases (Box 9-2).CeramideO AntigenGlc WGal WGalNAcW Gal WGalNAc)A AntigenB AntigenFigure 9-11 The human blood groups (O, A, B)are determined in part by the sugar head groups inthese glycosphingolipids. The same three types ofcomplex sugar groups are also found attached tocertain blood proteins of individuals of blood typesO, A, and B, respectively.
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