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You are watching: The cholesterol associated with animal cell membranes

Cooper GM. The Cell: A molecule Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000.


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Like all various other cellular membranes, the plasma membrane consists of both lipids and also proteins. The fundamental structure that the membrane is the phospholipid bilayer, which develops a stable obstacle between 2 aqueous compartments. In the case of the plasma membrane, these compartments room the inside and the exterior of the cell. Proteins embedded within the phospholipid bilayer lug out the details functions that the plasma membrane, consisting of selective transfer of molecules and cell-cell recognition.


The Phospholipid Bilayer

The plasma membrane is the most thoroughly learned of all cell membranes, and it is mainly through investigations of the plasma membrane the our current principles of membrane structure have actually evolved. The plasma membranes of mammalian red blood cell (erythrocytes) have been particularly useful as a version for researches of membrane structure. Mammalian red blood cells execute not save on computer nuclei or inner membranes, therefore they represent a resource from which pure plasma membranes have the right to be conveniently isolated because that biochemical analysis. Indeed, researches of the red blood cell plasma membrane provided the an initial evidence that biological membranes covers lipid bilayers. In 1925, 2 Dutch scientists (E. Gorter and also R. Grendel) extracted the membrane lipids from a known variety of red blood cells, equivalent to a known surface area of plasma membrane. Castle then established the surface area populated by a monolayer the the extracted lipid spread out at an air-water interface. The surface area of the lipid monolayer turned the end to be double that populated by the erythrocyte plasma membranes, bring about the conclusion that the membranes consisted of lipid bilayers quite than monolayers.

The bilayer structure of the erythrocyte plasma membrane is plainly evident in high-magnification electron micrographs (Figure 12.1). The plasma membrane shows up as two thick lines be separated by an intervening space—a morphology typically referred to as a “railroad track” appearance. This picture results from the binding that the electron-dense heavy metals supplied as stains in infection electron microscopy (see thing 1) to the polar head teams of the phospholipids, which therefore show up as dark lines. These thick lines room separated by the lightly stained interior portion of the membrane, which includes the hydrophobic fatty mountain chains.


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Figure 12.1

Bilayer framework of the plasma membrane. Electron micrograph the a human red blood cell. Keep in mind the railroad monitor appearance of the plasma membrane. (Courtesy that J. David Robertson, fight it out University clinical Center.)


As debated in thing 2, the plasma membranes of animal cells save on computer four major phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin), which together account for an ext than fifty percent of the lipid in most membranes. These phospholipids space asymmetrically distributed in between the 2 halves that the membrane bilayer (Figure 12.2). The external leaflet of the plasma membrane consists mainly the phosphatidylcholine and sphingomyelin, conversely, phosphatidylethanolamine and phosphatidylserine are the primary phospholipids the the within leaflet. A fifth phospholipid, phosphatidylinositol, is likewise localized to the inner fifty percent of the plasma membrane. Return phosphatidylinositol is a quantitatively boy membrane component, it plays crucial role in cell signaling, as disputed in the following chapter. The head groups of both phosphatidylserine and phosphatidylinositol room negatively charged, so their predominance in the inside leaflet outcomes in a net an adverse charge top top the cytosolic confront of the plasma membrane.


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Figure 12.2

Lipid contents of the plasma membrane. The outer leaflet consists predominantly that phosphatidylcholine, sphingomyelin, and also glycolipids, whereas the within leaflet contains phosphatidylethanolamine, phosphatidylserine, and also phosphatidylinositol. Cholesterol (more...)


In addition to the phospholipids, the plasma membranes of pet cells save glycolipids and also cholesterol. The glycolipids are uncovered exclusively in the external leaflet that the plasma membrane, v their carbohydrate parts exposed on the cabinet surface. Castle are relatively minor membrane components, constituting only around 2% that the lipids of most plasma membranes. Cholesterol, on the other hand, is a major membrane ingredient of pet cells, being existing in around the same molar amounts as the phospholipids.

Two general features of phospholipid bilayers are critical to membrane function. First, the structure of phospholipids is responsible because that the basic function of membranes as barriers between two aqueous compartments. Because the internal of the phospholipid bilayer is populated by hydrophobic fatty acid chains, the membrane is impermeable come water-soluble molecules, including ions and most organic molecules. Second, bilayers of the naturally arising phospholipids are viscous fluids, no solids. The fatty acids of most natural phospholipids have actually one or more dual bonds, which introduce kinks right into the hydrocarbon chains and also make them daunting to pack together. The lengthy hydrocarbon chains of the fatty acids because of this move easily in the interior of the membrane, for this reason the membrane itself is soft and flexible. In addition, both phospholipids and also proteins are cost-free to diffuse laterally within the membrane—a residential property that is critical for countless membrane functions.

Because of its strict ring structure, cholesterol dram a distinct duty in membrane structure. Cholesterol will not kind a membrane by itself, but inserts right into a double layer of phospholipids v its polar hydroxyl team close to the phospholipid head groups (see figure 12.2). Depending upon the temperature, cholesterol has unique effects ~ above membrane fluidity. At high temperatures, cholesterol interferes v the motion of the phospholipid fatty mountain chains, make the outer part of the membrane much less fluid and also reducing the permeability to little molecules. At low temperatures, however, cholesterol has the the contrary effect: through interfering with interactions in between fatty mountain chains, cholesterol stays clear of membranes indigenous freezing and maintains membrane fluidity. Back cholesterol is not existing in bacteria, that is an essential component of animal cell plasma membranes. Plant cells likewise lack cholesterol, however they contain associated compounds (sterols) that fulfill a similar function.

Recent studies suggest that no all lipids diffuse freely in the plasma membrane. Instead, discrete membrane domains show up to be enriched in cholesterol and also the sphingolipids (sphingomyelin and glycolipids). These clusters the sphingolipids and cholesterol room thought to type “rafts” that relocate laterally in ~ the plasma membrane and also may associate with particular membrane proteins. Back the attributes of lipid rafts remain to be understood, they may play essential roles in processes such as cell signaling and also the absorb of extracellular molecule by endocytosis.


Membrane Proteins

While lipids space the fundamental structural elements of membranes, proteins room responsible for carrying out specific membrane functions. Many plasma membranes consist of approximately 50% lipid and also 50% protein by weight, through the carbohydrate sections of glycolipids and glycoproteins constituting 5 come 10% the the membrane mass. Due to the fact that proteins room much bigger than lipids, this percentage corresponds to around one protein molecule every every 50 come 100 molecules of lipid. In 1972, Jonathan Singer and also Garth Nicolson suggest the fluid mosaic design of membrane structure, which is currently generally accepted as the simple paradigm for the company of all biological membranes. In this model, membrane are regarded as two-dimensional fluids in which proteins are inserted into lipid bilayers (Figure 12.3).


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Figure 12.3

Fluid mosaic version of the plasma membrane. Integral membrane protein are placed into the lipid bilayer, conversely, peripheral proteins are bound come the membrane indirectly by protein-protein interactions. Many integral membrane proteins are transmembrane (more...)


Singer and also Nicolson identified two class of membrane-associated proteins, which they dubbed peripheral and also integral membrane proteins. Peripheral membrane proteins were operationally characterized as proteins the dissociate indigenous the membrane following treatments v polar reagents, together as solutions of too much pH or high salt concentration, that carry out not disrupt the phospholipid bilayer. As soon as dissociated indigenous the membrane, peripheral membrane proteins space soluble in aqueous buffers. These proteins are not put into the hydrophobic internal of the lipid bilayer. Instead, they are indirectly linked with membranes with protein-protein interactions. These interactions generally involve ionic bonds, which room disrupted by extreme pH or high salt.

In contrast to the peripheral membrane proteins, integral membrane proteins deserve to be released only by therapies that disrupt the phospholipid bilayer. Parts of these integral membrane proteins are placed into the lipid bilayer, for this reason they can be dissociated only by reagents that disrupt hydrophobic interactions. The most frequently used reagents because that solubilization the integral membrane proteins space detergents, which are tiny amphipathic molecule containing both hydrophobic and hydrophilic teams (Figure 12.4). The hydrophobic sections of detergents displace the membrane lipids and bind to the hydrophobic portions of integral membrane proteins. Since the other end of the laundry detergent molecule is hydrophilic, the detergent-protein complexes are soluble in aqueous solutions.


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Figure 12.4

Solubilization that integral membrane proteins by detergents. Detergents (e.g., octyl glucoside) room amphipathic molecule containing hydrophilic head groups and hydrophobic tails. The hydrophobic tails bind to the hydrophobic regions of integral membrane (more...)


Many integral proteins room transmembrane proteins, which expectations the lipid double layer with parts exposed top top both political parties of the membrane. These proteins deserve to be visualized in electron micrographs of plasma membranes all set by the freeze-fracture method (see number 1.35). In this specimens, the membrane is split and separates into its 2 leaflets. Transmembrane proteins are then apparent as corpuscle on the internal encounters of the membrane (Figure 12.5).


Figure 12.5

Freeze-fracture electron micrograph of human red blood cabinet membranes. The particles in the membrane space transmembrane proteins. (Harold H. Edwards/Visuals Unlimited.)


The membrane-spanning parts of transmembrane proteins room usually α helices the 20 come 25 hydrophobic amino acids the are placed into the membrane the the absorbent reticulum during synthesis the the polypeptide chain (see figures 9.11, 9.12, and also 9.13). These proteins space then transported in membrane vesicles native the absorbent reticulum come the Golgi apparatus, and also from over there to the plasma membrane. Carbohydrate teams are included to the polypeptide chain in both the endoplasmic reticulum and also Golgi apparatus, so many transmembrane proteins of the plasma membrane are glycoproteins with their oligosaccharides exposed ~ above the surface ar of the cell.

Studies the red blood cells have provided great examples of both peripheral and also integral proteins linked with the plasma membrane. The membrane of person erythrocytes contain around a dozen major proteins, which were originally determined by gel electrophoresis of membrane preparations. Most of these room peripheral membrane proteins that have actually been determined as contents of the cortical cytoskeleton, i m sorry underlies the plasma membrane and determines cell shape (see thing 11). Because that example, the most abundant peripheral membrane protein the red blood cells is spectrin, i m sorry is the significant cytoskeletal protein that erythrocytes. Various other peripheral membrane proteins of red blood cells incorporate actin, ankyrin, and also band 4.1. Ankyrin serves as the principal link between the plasma membrane and also the cytoskeleton through binding to both spectrin and the integral membrane protein band 3 (see figure 11.11). An additional link in between the membrane and the cytoskeleton is provided by tape 4.1, which binding to the junctions that spectrin and actin, and also to glycophorin (the other major integral membrane protein the erythrocytes).

The two major integral membrane protein of red blood cells, glycophorin and also band 3, provide well-studied examples of transmembrane protein framework (Figure 12.6). Glycophorin is a tiny glycoprotein the 131 amino acids, v a molecular load of about 30,000, fifty percent of which is protein and fifty percent carbohydrate. Glycophorin crosses the membrane with a single membrane-spanning α helix that 23 amino acids, v its glycosylated amino-terminal section exposed on the cell surface. Return glycophorin was one of the very first transmembrane protein to it is in characterized, its precise function continues to be unknown. In contrast, the duty of the other major transmembrane protein that red blood cell is fine understood. This protein, originally recognized as band 3, is the anion transporter responsible because that the passage of bicarbonate (HCO3-) and chloride (Cl-) ions throughout the red blood cell membrane. The tape 3 polypeptide chain is 929 amino acids and also is thought to have actually 14 membrane-spanning α-helical regions. Within the membrane, dimers of tape 3 kind globular frameworks containing internal channels through i beg your pardon ions are able come travel across the lipid bilayer.


Figure 12.6

Integral membrane protein of red blood cells. Glycophorin (131 amino acids) has a solitary transmembrane α helix. That is greatly glyocosylated, v oligosaccharides attached come 16 sites on the extracellular portion of the polypeptide chain. (more...)


Because of their amphipathic character, transmembrane proteins have actually proved difficult to crystallize, as forced for three-dimensional structural evaluation by X-ray diffraction. The an initial transmembrane protein to be analyzed by X-ray crystallography was the photosynthetic reaction facility of the bacterium Rhodopseudomonas viridis, whose framework was report in 1985 (Figure 12.7). The reaction facility contains 3 transmembrane proteins, designated L, M, and also H (light, medium, and also heavy) according to their evident sizes suggested by gelatin electrophoresis. The L and also M subunits every have five membrane-spanning α helices. The H subunit has actually only a single transmembrane α helix, with the bulk of the polypeptide chain top top the cytosolic side of the membrane. The fourth subunit of the reaction center is a cytochrome, i beg your pardon is a peripheral membrane protein bound come the facility by protein-protein interactions.


Figure 12.7

A bacter photosynthetic reaction center. The reaction facility consists of three transmembrane proteins, designated l (red), M (yellow), and also H (green). The L and M subunits each have five transmembrane α helices, whereas the H subunit has only (more...)


Although most transmembrane proteins expectancy the membrane through α-helical regions, this is not always the case. A well-characterized exception is detailed by the porins—a course of protein that kind channels in the outer membranes of part bacteria. Plenty of bacteria, consisting of E. Coli, have a double membrane mechanism in i beg your pardon the plasma membrane (or inner membrane) is surrounding by the cell wall surface and a distinctive outer membrane (Figure 12.8). In contrast to the plasma membrane, the outer membrane is very permeable to ions and little polar molecule (in the case of E. Coli, through molecular weights up to 600). This permeability outcomes from the porins, which type open aqueous networks through the lipid bilayer. As debated in chapter 10, proteins regarded the bacterial porins are additionally found in the outer membranes the mitochondria and chloroplasts.


Figure 12.8

Bacterial outer membranes. The plasma membrane of part bacteria is surrounding by a cell wall surface and a unique outer membrane. The external membrane consists of porins, which form open aqueous channels allowing the totally free passage of ions and small molecules.


Structural analysis has suggested that the porins perform not save hydrophobic α-helical regions. Instead, they overcome the membrane as β barrels, in i beg your pardon 16 β sheets wrinkles up into a barrel-like structure enclosing an aqueous spicy (Figure 12.9). The side chains that polar amino acids line the pore, whereas side chains of hydrophobic amino acids connect with the internal of the membrane. The porin monomers associate to type stable trimers, every of which contains three open channels through which polar molecules have the right to diffuse throughout the membrane.


Figure 12.9

Structure of a porin monomer. Every monomer is a β barrel consists of 16 antiparallel β strands (arrows). The top finish of the molecule faces the external medium. (From H. Nikaido, 1994. J. Biol. Chem. 269: 3905.)


In contrast to transmembrane proteins, a variety of proteins (many of i m sorry behave as integral membrane proteins) room anchored in the plasma membrane by covalently attached lipids or glycolipids (Figure 12.10). Members of one course of these proteins are inserted into the external leaflet of the plasma membrane through glycosylphosphatidylinositol (GPI) anchors. GPI anchors are included to specific proteins that have actually been transferred right into the endoplasmic reticulum and are anchored in the membrane through a C-terminal transmembrane an ar (see number 9.16). The transmembrane region is cleaved together the GPI anchor is added, so these proteins remain attached to the membrane just by the glycolipid. Due to the fact that the polypeptide chain of GPI-anchored proteins room transferred right into the endoplasmic reticulum, they are glycosylated and also exposed ~ above the surface of the cell adhering to transport come the plasma membrane.


Figure 12.10

Examples of proteins anchored in the plasma membrane by lipids and glycolipids. Part proteins (e.g., the lymphocyte protein Thy-1) are anchored in the outer leaflet of the plasma membrane through GPI anchors added to their C terminus in the endoplasmic reticulum. (more...)


Other proteins room anchored in the within leaflet of the plasma membrane by covalently enclosed lipids. Quite than being processed with the secretory pathway, these proteins are synthesized on cost-free cytosolic ribosomes and also then modification by the enhancement of lipids. These modifications include the addition of myristic acid (a 14-carbon fat acid) to the amino terminus that the polypeptide chain, the enhancement of palmitic acid (16 carbons) to the next chains the cysteine residues, and the addition of prenyl teams (15 or 20 carbons) to the side chains of carboxy-terminal cysteine residues (see numbers 7.29, 7.30, and 7.31). In some cases, this proteins (many of i m sorry behave together peripheral membrane proteins) room targeted come the plasma membrane by positive charged regions of the polypeptide chain and also by the attached lipids. These positively fee protein domain names may interact with the negatively fee head teams of phosphatidylserine on the cytosolic challenge of the plasma membrane. The is remarkable that numerous of the protein anchored in the inner leaflet that the plasma membrane (including the Src and Ras proteins portrayed in number 12.10) play vital roles in the transmission of signal from cell surface ar receptors to intracellular targets, as disputed in the next chapter.


Mobility of Membrane Proteins

Membrane proteins and also phospholipids space unable to move earlier and forth in between the inner and also outer leaflets that the membrane at an appreciable rate. However, because they are inserted into a fluid lipid bilayer, both proteins and lipids are able come diffuse laterally with the membrane. This lateral motion was first shown straight in one experiment reported by Larry Frye and also Michael Edidin in 1970, which listed support for the fluid mosaic model. Frye and also Edidin unify human and also mouse cells in society to develop human-mouse cabinet hybrids (Figure 12.11). They then analyzed the distribution of proteins in the membranes of this hybrid cells utilizing antibodies the specifically acknowledge proteins that human and mouse origin. These antibodies were labeled with various fluorescent dyes, therefore the human and mouse proteins might be differentiated by fluorescence microscopy. Automatically after fusion, human and also mouse proteins were localized to various halves of the hybrid cells. However, after ~ a brief period of incubation at 37°C, the human and also mouse proteins were completely intermixed end the cell surface, indicating the they moved openly through the plasma membrane.


Figure 12.11

Mobility of membrane proteins. Human and also mouse cells were fused to develop hybrid cells. The distribution of cell surface ar proteins was then analyzed using anti-human and anti-mouse antibodies labeling with different fluorescent water (red and also green, respectively). (more...)


However, not all proteins space able to diffuse freely through the membrane. In some cases, the mobility of membrane proteins is minimal by your association v the cytoskeleton. Because that example, a portion of tape 3 in the red blood cabinet membrane is immobilized together a result of the association through ankyrin and spectrin. In other cases, the mobility the membrane proteins may be minimal by their associations with various other membrane proteins, through proteins on the surface ar of adjacent cells, or with the extracellular matrix.

In comparison to blood cells, epithelial cells space polarized as soon as they space organized into tissues, with various parts that the cabinet responsible for performing unique functions. Consequently, the plasma membranes of countless epithelial cells are separated into distinct apical and basolateral domain names that different in role and protein ingredient (Figure 12.12). For example, epithelial cells of the tiny intestine function to absorb nutrient from the cradle tract. The apical surface of these cells, which faces the intestinal lumen, is thus covered by microvilli and devoted for nutrient absorption. The basolateral surface, which deals with underlying connective tissue and the blood supply, is specialized to adjust the move of took in nutrients right into the circulation. In stimulate to preserve these distinctive functions, the mobility that plasma membrane proteins need to be limited to the suitable domains that the cabinet surface. At least component of the mechanism whereby this occurs involves the development of tight junctions (which are questioned later in this chapter) between adjacent cells of the epithelium. These junctions not only seal the an are between cells but additionally serve as barriers to the motion of membrane lipids and also proteins. Together a result, proteins space able come diffuse in ~ either the apical or basolateral domain names of the plasma membrane but are no able to cross from one domain come the other.


Figure 12.12

A polarized minister epithelial cell. The apical surface of the cell has microvilli and also is devoted for absorb of nutrient from the intestinal lumen. The basolateral surface ar is specialized for the transport of took in nutrients come the basic (more...)


The Glycocalyx

As currently discussed, the extracellular parts of plasma membrane protein are typically glycosylated. Likewise, the carbohydrate parts of glycolipids space exposed ~ above the outer confront of the plasma membrane. Consequently, the surface of the cell is extended by a carbohydrate coat, known as the glycocalyx, developed by the oligosaccharides that glycolipids and also transmembrane glycoproteins (Figure 12.13).


Figure 12.13

The glycocalyx. An electron micrograph of minister epithelium illustrating the glycocalyx (arrows). (Don Fawcett/ Visuals Unlimited.)


Part the the function of the glycocalyx is to safeguard the cabinet surface. In addition, the oligosaccharides of the glycocalyx serve as markers for a variety of cell-cell interactions. A well-studied example of this interactions is the adhesion the white blood cells (leukocytes) to the endothelial cells that line blood vessels—a process that allows the leukocytes to leave the circulatory system and mediate the inflammatory solution in injured tissues. The initial action in adhesion in between leukocytes and also endothelial cell is mediated by a family of transmembrane proteins called selectins, which recognize certain carbohydrates ~ above the cell surface (Figure 12.14). 2 members of the selectin family (E-selectin and also P-selectin), express by endothelial cells and platelets, tie to specific oligosaccharides expressed on the surface of leukocytes. A various selectin (L-selectin) is express by leukocytes and recognizes an oligosaccharide on the surface of endothelial cells. The oligosaccharides exposed top top the cell surface ar thus administer a set of markers that aid identify the distinctive cell types of multicellular organisms.

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Figure 12.14

Binding the selectins come oligosaccharides. E-selectin is a transmembrane protein expressed by endothelial cells that binding to one oligosaccharide express on the surface of leukocytes. The oligosaccharide well-known by E-selectin contains N-acetylglucosamine (more...)


By agreement with the publisher, this publication is obtainable by the search feature, yet cannot it is in browsed.