Structural Lipids Biochemistry PDF

# Structural Lipids ## Introduction The same hydrophobic interactions that drive lipid droplet formation in triglycerides also drive certain lipids to form biochemically important structures, including micelles, lipid monolayers, and lipid bilayers. Lipid bilayers are especially important as major...

# Structural Lipids ## Introduction The same hydrophobic interactions that drive lipid droplet formation in triglycerides also drive certain lipids to form biochemically important structures, including micelles, lipid monolayers, and lipid bilayers. Lipid bilayers are especially important as major components of biological membranes. The lipids found in membranes and related structures are amphiphilic, meaning they contain both a hydrophobic region and a hydrophilic region. This property allows these lipids to interact with both aqueous and hydrophobic environments by orienting themselves accordingly. Figure 9.10 shows examples of amphiphilic lipids forming membranes and membrane-like structures. ## Micelle - Hydrophobic molecules - Aqueous environment ## Lipid Monolayer ## Lipid Bilayer ## 9.2.01 Glycerophospholipids The most common lipid component of lipid bilayer membranes is the phospholipid. There are two major types of phospholipids: glycerophospholipids and sphingophospholipids. Of these types, glycerophospholipids are more common, and the term "phospholipids" is often used to refer to glycerophospholipids in particular. This concept covers the structure and functions of glycerophospholipids; sphingolipids are discussed in Concept 9.2.02. ## General Structure of Phospholipids The name glycerophospholipid hints at the molecule's structure-glycerophospholipids are lipids with a glycerol backbone attached to a phosphate group. Lesson 9.1 discussed how a triglyceride is composed of a glycerol backbone with three fatty acids esterified onto its three hydroxyl groups. A glycerophospholipid has a structure similar to a triglyceride, but it is esterified with only two fatty acids; the third hydroxyl group of glycerol is attached to a phosphate group. Figure 9.11 compares the structures of a triglyceride and a glycerophospholipid. ### Triglyceride - Glycerol Backbone - H - O - H-C-O-C-R - C - O=C O=C - O - H-C-O-C-R - O - H-C-O-C-R - H - Three fatty acyl groups ### Glycerophospholipid - Glycerol Backbone - H - O - H-C-O-P-O-R' - C - O= - H-C-O-C-R - O - H-C-O-C-R - H - Phosphate group - Two fatty acyl groups ## Phospholipid Tails Glycerophospholipids consist of a head group and two tail groups. The tail groups come from the hydrophobic tails of the fatty acyl groups esterified onto the glycerol backbone. In membrane lipids, the tails may consist of any number of carbons but are commonly long-chain fatty acids (ie, 14 to 24 carbon atoms). The tails may have no double bonds (which makes them saturated) or at least one double bond (which makes them unsaturated). The saturation of the fatty acid tails has important implications for membrane fluidity (Concept 9.2.08). Note that the tails on a glycerophospholipid do not need to be the same type of fatty acid. Figure 9.12 shows a common depiction of a glycerophospholipid with two different tail groups. ## Phospholipid Head Groups The head group of a glycerophospholipid consists of the phosphate group and anything to which the phosphate is attached (ie, the R' group shown in Figure 9.11). If the R' group is simply an H atom, then the molecule is phosphatidic acid (phosphate + lipid + -ic acid). The R' position can be replaced by a variety of different groups. For example, if R' comes from ethanolamine (ie, R' = −OCH2CH2NH3+), the molecule is phosphatidylethanolamine (ie, ethanolamine with a phosphatidyl substituent). These R' groups are typically polar molecules and contribute to the hydrophilic character of the phospholipid head group. Figure 9.13 shows examples of common head groups that appear on glycerophospholipids. | Head group charge | Phosphatidyl- | |---|---| | Zwitterionic (neutral) | -ethanolamine | | Zwitterionic (neutral) | -choline | | Negative | -glycerol | | Negative | -serine | | Negative | -inositol | In Figure 9.13, the phospholipids are divided into two groups: those with a zwitterionic head group and those with a negative head group. Zwitterions are compounds with an equal number of positive and negative charges and therefore have a net neutral charge. Both phosphatidylethanolamine (PE) and phosphatidylcholine (PC) have positively charged amine groups (a primary amine and a quaternary amine, respectively), which cancel the remaining negative charge of the phosphate group. Therefore, PE and PC have zwitterionic head groups. In contrast, phosphatidylglycerol (PG) and phosphatidylinositol (PI) have neutral R' substituents. With no positive charge to offset the negative charge of the phosphate group, these phospholipids have negatively charged head groups. The zwitterionic R' substituent of phosphatidylserine (PS) combined with the negative phosphate charge gives the PS head group an overall negative charge as well. ## Head Groups Can Be Glycosylated to Form a Glycolipid In addition to the small molecule head groups shown in Figure 9.13, the head groups can be further modified through the addition of carbohydrate groups. For example, the reducing end of an oligosaccharide can form a glycosidic bond to one of the -OH groups of the phosphatidylinositol (PI) headgroup, as shown in Figure 9.14. The resulting molecule, comprising both a lipid and a carbohydrate, is called a glycolipid. The glycolipid glycosylphosphatidylinositol (GPI) can be further attached to certain proteins to form a lipid anchor that permanently attaches the protein to the membrane (Figure 9.14). ## 9.2.02 Sphingolipids Sphingolipids—both in their phosphorylated and nonphosphorylated variants are another major component of amphipathic membranes. Unlike glycerophospholipids, which have a glycerol backbone, sphingolipids have the molecule sphingosine as their backbone. Sphingosine is compared to glycerol in Figure 9.15. ## Sphingolipids Can Have Various Head Groups Like glycerophospholipids, sphingolipids can have various head groups. Figure 9.16 shows that the head group is attached to the C1 hydroxyl position of sphingosine in a position analogous to that of the phosphate head group of glycerophospholipids. Sphingolipids that have an -H group as the head group are called ceramides, highlighting the amide bond connecting sphingosine to its attached fatty acid. Sphingophospholipids are similar to glycerophospholipids and have a phosphate group as the head group. The phosphate may be further substituted, just as with glycerophospholipids. Sphingophospholipids with a phosphocholine or phosphoethanolamine head group are classified as the zwitterionic sphingomyelins. Sphingomyelins are particularly common in the myelin sheath surrounding the axons of neurons (see Figure 9.17). ## Glycosphingolipids Glycosphingolipids have carbohydrates as the sphingolipid head group and are connected by glycosidic bonds between the C1 hydroxyl and the anomeric carbon of the carbohydrate. The carbohydrate head group of these glycolipids can be a simple monosaccharide (eg, the cerebrosides), a longer oligosaccharide (eg, the globosides), or more complex polysaccharides that include sialic acid derivatives (eg, the gangliosides). Importantly, these glycosphingolipids are not phospholipids because they do not have phosphate groups; however, they still are important components of cell membranes. The classifications of sphingolipids based on head group are summarized in Figure 9.18. ## 9.2.03 Cholesterol Cholesterol is the final major membrane lipid discussed in this lesson. Several representations of the structure of cholesterol are shown in Figure 9.19. ## 9.2.04 Waxes Unlike most of the structural lipids described in this lesson, waxes are not membrane lipids. However, waxes serve a structurally supportive role as a protective coating for hair and skin in humans, and they also serve an energy storage role in other organisms. Structurally, a biological wax is the ester of a long-chain fatty acid and a long-chain alcohol. Unlike glycerol, the alcohol component of a wax has only a single primary alcohol group with no other functional group. Figure 9.25 shows the structure of a biological wax. ## 9.2.05 Organization of Structural Lipids ## Some Amphiphiles Organize as Micelles and Act as Detergents Many amphiphilic molecules, such as fatty acids, form spherical structures called micelles when placed in an aqueous solution. Micelles are organized with the hydrophobic portions of each molecule oriented toward the center of the sphere and the hydrophilic portions oriented outward. The general structure of a micelle is shown in Figure 9.26. ## Other Amphiphiles Organize into Layers Not all amphiphilic molecules organize into spherical micelles. Phospholipids, for example, are amphiphilic molecules that organize into flatter layers. An individual lipid layer (ie, a monolayer) organizes with the hydrophilic components on the aqueous side and the hydrophobic components on the nonaqueous side. Monolayers can serve as the barrier between an aqueous solution and a hydrophobic aggregate. For example, lipid droplets in a cell and lipoprotein particles in the blood are typically enclosed in a phospholipid monolayer. By enclosing lipid aggregates, phospholipid monolayers eliminate the need for a highly ordered solvation layer, as shown in Figure 9.27. ## 9.2.06 Properties of Lipid Bilayers ### Lipid Bilayer Membranes Are Semipermeable Lipid bilayer membranes separate two aqueous compartments from each other (eg, the cytosol from the extracellular space, the lumen of an organelle from the cytosol). Most solutes dissolved in an aqueous compartment cannot easily cross through a lipid bilayer by themselves. In contrast, small hydrophobic molecules (eg, dissolved gases) can cross a lipid bilayer because they interact more favorably with the lipid tails (see Figure 9.29). ### Membranes Are Asymmetric Although the individual molecules in a membrane have free lateral diffusion (see Concept 9.2.07), they do not experience free transverse diffusion. In other words, a plasma membrane phospholipid in the outer leaflet (where its hydrophilic head group faces the extracellular solution) cannot freely diffuse into the inner leaflet (where its hydrophilic head group would face the cytosol) (Figure 9.31). Similarly, membrane proteins cannot flip the orientations of their extracellular and intracellular domains. ## 9.2.07 The Fluid Mosaic Model ### The Fluid Mosaic Model Cell membranes consist of amphiphilic lipids and membrane proteins. The amphiphilic lipids include both phospholipids and cholesterol, and the membrane proteins include both transporters (Lesson 3.3) and nontransport membrane proteins (eg, transmembrane receptors, Concept 3.2.02). Although lipids are often classified as macromolecules, they are not polymers. Unlike proteins (amino acids joined by peptide bonds), polysaccharides (monosaccharides joined by glycosidic bonds), and nucleic acids (nucleotides joined by phosphodiester linkages), the individual lipids in a lipid aggregate such as a membrane are not covalently bonded to each other. Because of this, membrane lipids and membrane proteins have free lateral diffusion throughout the bilayer. In other words, individual lipid molecules or membrane proteins can move side-to-side or back-to-front across a lipid bilayer, as shown in Figure 9.32. ## 9.2.08 Determinants of Fluidity The fluidity of a membrane is essential to its function in cell biology. A membrane that is too rigid (ie, solid-like) is prone to breakage upon deformation, whereas a membrane that is too flexible and fluid is prone to increased permeability and leakage. External temperature is one factor that influences membrane fluidity. Like all matter, as the temperature of the membrane increases, its fluidity also increases. Individual cells cannot control external temperature. However, cells can influence membrane fluidity by controlling the composition of a membrane in response to temperature changes. By altering the types of lipids included in a membrane, membrane fluidity can increase, decrease, or be buffered against fluidity changes. Broadly speaking, membrane fluidity is controlled by the strength of the intermolecular forces (IMFs) between the membrane components. ### Influence of Phospholipid Fatty Acyl Tails Membrane phospholipids may be attached to a variety of fatty acids to form the phospholipid tails. Fatty acid tails vary in length, but commonly range between 14 to 24 carbons (Concept 9.2.01). Furthermore, fatty acids can be saturated or unsaturated, depending on the presence of carbon-carbon double bonds in the hydrocarbon tail. Both factors affect the intermolecular London dispersion forces holding the membrane together; therefore, the properties of the phospholipid fatty acyl groups have a significant impact on membrane fluidity. Increasing tail length causes stronger IMFs because there are more atoms available to interact. Consequently, phospholipids with longer tails are more viscous and therefore less fluid. In contrast, shorter tails lead to more fluidity (Figure 9.37). ### Cholesterol Is a Membrane Fluidity Buffer Cholesterol has an interesting effect on membrane fluidity. The fused ring structure causes cholesterol to be relatively rigid, inflexible, and conformationally locked. Because of this, cholesterol's presence can make the membrane itself more rigid and inflexible and can therefore decrease the fluidity of overly fluid membranes. However, cholesterol's unique structure does not pack tightly with most lipid components in the membrane. Because cholesterol interrupts the packing interactions between the phospholipid tails of other membrane lipids, cholesterol can also increase the fluidity of overly rigid membranes. Because cholesterol can both increase and decrease membrane fluidity, cholesterol can be thought of as a buffer of membrane fluidity that prevents changes away from an optimal level (Figure 9.39). ### Membrane Composition Can Change in Response to Temperature Membrane composition is not static. If external temperatures change a cell's membrane fluidity, the cell can alter its membrane composition in a homeostatic response to restore its preferred level of fluidity. For example, if the temperature rises and a cell's membrane fluidity increases, the cell can increase the average length and proportion of saturated fatty acids in the membrane to bring fluidity down (see Figure 9.40). ## Lipid Rafts Are Localized Microdomains in Biological Membranes Despite lateral diffusion, a given leaflet of a biological membrane does not necessarily have a homogeneous (ie, evenly spread) distribution of its membrane components. Some membranous components self-assemble into microdomains known as lipid rafts. Lipid rafts are localized regions of the membrane that are rich in the less fluid components of the membrane bilayer. For example, compared to the surrounding membrane, lipid rafts tend to be enriched in sphingolipids, cholesterol, and glycerophospholipids with long, saturated fatty acid tails. Figure 9.36 shows a visual depiction of a lipid raft. Lipid rafts can serve to group membrane proteins together, increasing the activity of the metabolic pathway they are involved in.