biochem chapter 12 lipids

Membrane Fluidity is Controlled by Fatty Acid Composition and Cholesterol Content

Membrane processes depend on the fluidity of the membrane. • The temperature at which a membrane transitions from being highly ordered to very fluid is called the melting temperature (Tm). • The melting temperature is dependent on the length of the fatty acids(longer=more rigid) in the membrane lipid and the degree of cis unsaturation(no double bond=more rigid, forms more intermolecular bonds this way ) . • Cholesterol helps to maintain proper membrane fluidity in membranes in animals forms complexes with glycosphingosines to form lipid rafts fluidity is determined by the relative movement of lipids, the stronger the interactions, the more rigid the molecule is as T increases, kinetic energy of lipids increase and they are no longer ordered and maintained. slide 55 slide 56 slide 57

Amino Acid Sequence of Bacteriorhodopsin

Membrane-spanning a helices are the most common structural motif in membrane proteins. • As expected, the bacteriorhodopsin a helices contain predominantly hydrophobic residues, while polar and charged residues tend to be found in the cytoplasmic and extracellular regions. tailormade with hydrophilic outside membrane protein are difficult to identify and crystalize

Proteins Interact With Membranes in a Variety of Ways

Membrane-spanning α helices are a common structural feature of integral membrane proteins. - Example: bacteriorhodopsin, a light-powered proton pump, is an integral membrane protein composed of seven membrane-spanning helices residues on outside are hydrophilic linked by loops and coils 20 AA residues length is just across membrane Integral membrane proteins may also be composed of β strands that form a pore in the membrane. • The bacterial protein porin is an example of a β strandrich integral membrane protein. • The outside surface of porin, which interacts with the hydrophobic interior of the membrane, is composed of hydrophobic amino acids. The inside is polar and filled with water. slide 38,39 open channel predict linked by loop regions clear patterns of hydrophobic residues interact membrane outside of overall structure

Many Common Features Underlie the Diversity of Biological Membranes

1. Membranes are sheetlike structures, two molecules thick, that form closed boundaries. 2. Membranes are composed of lipids and proteins, either of which can be decorated with carbohydrates. 3. Membrane lipids are small amphipathic molecules that form closed bimolecular sheets that prevent the movement of polar or charged molecules(phospholipid) 4. Proteins serve to mitigate the impermeability of membranes and allow movement of molecules and information across the cell membrane. (function as transporters, enzymes, receptors, moderate energy storage) 5. Membranes are noncovalent assemblies (hydrophobic interactions, small individually but aggregate makes it strong) 6. Membranes are asymmetric in that the outer surface is always different from the inner surface.( 2 faces are never identical) 7. Membranes are fluid structures, constant lateral movement due to weak intermolecular bonds 8. Most cell membranes are electrically polarized. biomolecules that form these are lipids main composition of membranes(induce electric dipole moments and thus voltage between sites) crucial biomolecule w important biological function separates cell from outside environment mature immune cells that separate antibodies slide 5

Transmembrane Helices Can be Accurately Predicted from Amino Acid Sequences

An α helix consisting of 20 residues can traverse a lipid bilayer. • Hydrophobicity of each amino acid can be quantified by determining the free energy required to transfer the amino acid from a hydrophobic to a hydrophilic environment. • A protein sequence can be examined by measuring the free energy of transferring each stretch of 20 amino acids, called a window, from a hydrophobic to a hydrophilic environment. • The free energy is plotted against the first amino acid of the window. Such a plot is called a hydropathy plot. • Hydropathy plots can identify potential membrane-spanning helices when sequence but little additional information is known for a protein. slide 48 plots hydrophobicity any above level is supposed to be inside protein

Aspirin's Effects on Prostaglandin H2 Synthase-1

Aspirin acts by transferring an acetyl group to a serine residue in prostaglandin H2 synthase-1.😊 slide 44, blocks excess of substrate

Membranes Can Fuse and Separate so that Cells and Compartments can Take Up, Transport, and Release Molecules

Cells can acquire molecules from their environment by receptormediated endocytosis. • The protein clathrin helps to internalize receptors bound to their cargo. • Fusion of internal membranes with the plasma membrane allows the release of molecules, such as neurotransmitters, from the cell. • The internalization of iron-bound transferrin in association with the transferrin receptor is an example of receptor-mediated endocytosis. • SNARE proteins facilitate membrane fusion by forming tightly coiled four-helical bundles neurotransmitter release: exocytosis, from surgace 2 neurons release chemical called neurotransmitter

Cholesterol is a Lipid Based on a Steroid Nucleus

Cholesterol is a steroid that is modified on one end by the attachment of a fatty acid chain and at the other end by a hydroxyl group. • In membranes, the hydroxyl group interacts with phospholipid head groups. rest of cholesterol lies in the membrane parallel to the nonpolar tails not a fatty acid anymore very hydrophobic 4 fused cyclic ring rigid

The Curious Case of Cardiolipin

Diphosphatidylglycerol (cardiolipin) has an unusual structure compared with the other phosphoglycerides shown earlier. • It has a net charge of −2 and an inverted cone shape, unlike most phosphoglycerides slide 71 Cardiolipin is most often found in the membranes of bacteria, archaea, and the inner membranes of mitochondria. In mitochondria, the cardiolipin is involved in the structure and function of the respirasome, which is essential in ATP synthesis. • Proper synthesis and maintenance of cardiolipin levels requires the enzyme tafazzin, which catalyzes the transfer of linoleate chains from phosphatidylcholine to immature cardiolipin. • Barth syndrome results from mutations that reduce the catalytic activity of tafazzin. Symptoms include dilation of the heart chambers, exercise intolerance, and impaired growth. These individuals have malformed mitochondria with distorted inner membranes and poorly functioning respirasomes due to improper assembly of the protein complexes

Eukaryotic Cells

Eukaryotic cells, with the exception of plants, do not have cell walls. They are surrounded by a single membrane, known as the plasma membrane (or cell membrane). • Eukaryotic cells have membranes inside the cell that allow compartmentalization of function. - Complex example: the nuclear envelope is a double membrane connected to another membrane system of eukaryotes, the endoplasmic reticulum Nuclear Envelope Connected to the Endoplasmic Reticulum slide 65.

Fatty Acids Are Key Constituents of Lipids

Fatty acids are chains of hydrogen-bearing carbon atoms that have a carboxylic acid at one end and a methyl group at the other end. • Fatty acids may be saturated or unsaturated. • Fatty acid carbon atoms are usually numbered beginning with the carboxyl terminal carbon atom. Carbon atoms 2 and 3 are also referred to as α and β, respectively. • Fatty acids can instead be numbered from the methyl carbon atom, which is called the omega (ω) carbon. vary in length, degrees of saturation and properties such as MP and fluidity double bonds not triple bonds triple bonds are unstable in body slide 7 hydrocarbons can rotate cis usually when double bonded biological systems doesnt have stable transfat helps prevent severe health issues slide 8

Fatty Acids Vary in Chain Length and Degree of Unsaturation

Fatty acids in biological systems usually contain an even number of carbon atoms, with the 16- and 18-carbon atom chains being the most common. • When double bonds are present, they are commonly in the cis configuration. In polyunsaturated fatty acids, the double bonds are separated by at least one methylene group. • The properties of fatty acids are dependent on chain length and degree of unsaturation. • Short chain length and the presence of cis double bonds enhance the fluidity of fatty acids linked double bonds together is too reactive trans can cause health concenrs longer chains have increased melting point because more VDW

Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane

Fluorescence recovery after photobleaching (FRAP) allows the measurement of lateral mobility of membrane components. • A membrane component is attached to a fluorescent molecule. On a very small portion of the membrane, the dye is subsequently destroyed by high-intensity light, thereby bleaching a portion of the membrane. • The mobility of the fluorescently labeled component is a function of how rapidly the bleached area recovers fluorescence. The average distance traveled S in time t depends on the diffusion constant D. S = (4Dt)1/2 • Lateral diffusion of proteins depends on whether they are attached to other cellular or extracellular components. diffuse readily slide 51 not static, move freely in constant horizontal motion. on graph you see at t=o, membrane is labeled w fluorescent t=T, region of the membrane is bleached with an empulse, destroying fluorescent overtime the lateral movement of the lipid will disperse the nonfluorescent molecules. this will retain the fluorecense to innitially bleached area the recovery of fluorescent confirms the lateral movement of lipids.

Membrane Lipids Can Include Carbohydrate Moieties

Glycolipids are carbohydrate-containing lipids derived from sphingosine. The carbohydrate is linked to the primary alcohol of sphingosine. • Cerebrosides (brain but also everywhere) are the simplest glycolipids, containing only a single sugar (glucose or galactose). • Gangliosides contain a branched chain of as many as seven sugar molecules. • The carbohydrate components of glycolipids are (usually) on the extracellular surface of the cell membrane, where they play a role in cell-cell recognition. addition of monosaccharide units to lipids slide 19 sphingosine acts as the backbone of attachment for a fatty acid and a carbohydrate component. THe sphingosine-fatty acid is the hydrophobic region that stretches across the nonpolar membrane while the carbohydrate moiety interacts with the aqueous cellular environment

Gram Staining of Bacteria

Gram-positive bacteria retain the crystal violet stain in their thick cell walls, while Gram-negative bacteria have a thinner cell wall that does not retain the stain well

Some Proteins Associate with Membranes Through Covalently Attached Hydrophobic Groups

Hydrophilic proteins can be made to associate with the membrane by attaching one of a variety of possible hydrophobic groups

Proteins Associate With the Lipid Bilayer in a Variety of Ways

Integral membrane proteins are embedded in the hydrocarbon core of the membrane (typically membrane spanning, portion within core interacts via VDW forces with hydrocarbon tails, considered transmembrane if goes all the way through) . • Peripheral membrane proteins are bound to the polar head groups of membrane lipids or to the exposed surfaces of integral membrane proteins held by h bonds or ionic bonds, readily dissociate given weaker interactions just add salt or lower ph) . • Some proteins are associated with membranes by attachment to a hydrophobic moiety that is inserted into the membrane. slide 34 mitochondria membrane contains a high percentage of proteins because the mitochondria functions in energy production cell membranes of most cells contain about 50% proteins

Lipid Vesicles Can Be Formed From Phospholipids

Liposomes, or lipid vesicles, are aqueous compartments enclosed by a lipid membrane. • Protein-liposome complexes can be used to investigate membrane protein functions. • Liposomes, formed by sonicating a mixture of phospholipids in aqueous solution, can be useful as drug delivery systems. • Planar bilayer membranes are also useful for examining membrane properties such as ion permeability in the presence of a voltage difference across the membrane outside and inside contain aqueous environment especially useful when drug isn't soluble slide 26 due to their amphipathic nature drug or dna delivery relatively small aqueous compartment that are surrounded by 2 phosphate lipid bilayer membrane

Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media

Membrane (bimolecular sheet) formation is a consequence of the amphipathic nature of the constituent lipid molecules. - Phospholipids and glycolipids, because of the space taken up by their two tails, do not form small micelles the way singletailed soap molecules do. - Rather, phospholipids and glycolipids spontaneously form lipid bilayers in aqueous solutions. • The hydrophobic effect drives membrane formation, and van der Waals interactions between the hydrophobic tails also stabilize membranes. There are also electrostatic and Hbonding attractions between the polar head groups and water molecules bilayer and micelle slide 24 Lipids spontaneously form micelles in water this occurs because it minimizes the polar nonpolar interactions between the aqueous environment and the hydrophobic tails. it allows the polar heads to interact w/ water and each other while hiding the nonpolar tails on the inside Bimolecular sheets form 2 layers, energetically favorable, forms when nonpolar tails of these lipids is too large to fit into the limited space of micelle

A Membrane Lipid is an Amphipathic Molecule Containing a Hydrophilic and a Hydrophobic Moiety

Membrane lipids are amphipathic molecules, containing hydrophobic and hydrophilic properties. • The fatty acid tail components provide the hydrophobic properties, whereas the alcohol and phosphate components, called the polar head group, provide the hydrophilic properties slide 22

Embedding Part of a Protein in a Membrane Can Link the Protein to the Membrane Surface

Only a portion of the enzyme prostaglandin H2 synthase1 is embedded in the membrane. • The cyclooxygenase (COX) activity of prostaglandin H2 synthase-1 is dependent on a channel connecting the active site to the membrane interior. • Aspirin inhibits cyclooxygenase activity by obstructing the channel. enzyme found on inner portion of the ER membrane. contains a hydrophobic region that binds tightly to the hydrophobic tails of membrane, integrat but transmembrane slide 41 varying hormone like effects naturally promotion of uterine contractions cyclic fatty acids slide 42 and 43

Common Alcohols Used in Making Phosphoglycerides

Phosphoglycerides are derived from phosphatidate by the formation of an ester bond between the phosphate and an alcohol. slide 16 the first 4 phospholipids form membranes cardiolipin is in mitochondria, they release from mitochondria to apoptosis C-1 and C-2 of glycerol is esterified to 2 fatty acids while c-3 is esterified to phosphate simplest is phosphatidate. it contains an unmodified phosphate group and is foundin the cell membrane in small quantities

Phospholipids Are the Major Class of Membrane Lipids

Phospholipids are composed of four components: one or two fatty acid tails, a platform, a phosphate, and an alcohol. • Two common platforms are glycerol and sphingosine. • Phospholipids with a glycerol platform are called phosphoglycerides or phosphoglycerols. They are formed when an alcohol is added on to phosphatidate (diacylglycerol 3-phosphate). AA links to fatty acid slide 13 and 14 fatty acid gives hydrophobic properties phosphate and alcohol give it hydrophilic properties, makes it amphipathic

Eukaryotic Cells Contain Compartments Bounded by Internal Membranes

Previous descriptions focused on plasma membranes. • Bacterial membranes are found in two main types, which can be distinguished by Gram staining: - Some bacteria and archaea are enclosed by a single membrane surrounded by a thick cell wall. These cells are sometimes referred to as Gram positive. - Other bacteria are surrounded by two membranes, with a cell wall (made of proteins, peptides, and carbohydrates) lying between them. The space between the two membranes is called the periplasm. These cells are Gram negative slide 62 gram negative double bilayer porins on outside membrane proteins have different functions and different architecture

Phospholipids May Also Be Built on a Sphingosine Platform

Sphingomyelin is a common membrane lipid in which the primary hydroxyl group of sphingosine is esterified to phosphorylcholine. slide 17 N of the sphingosine is bound to a fatty acid via an amide bond. while the primary alcohol is bound to the phosphate group via an ester bond

Myelination of a Neuron

The Schwann cell is an example of a cell type with relatively low membrane protein content. • Instead, its plasma membrane is lipid-rich; the lipid serves as an insulator, allowing rapid transmission of nerve impulses. • The wrapping of this type of cell around an axon is referred to as myelination. • Multiple sclerosis is an example of a demyelination disease, impairing myelin assembly or damaging existing myelin

Lipid Bilayers Are Highly Impermeable to Ions and Most Polar Molecules

The ability of small molecules to cross a lipid bilayer is a function of their hydrophobicity (lack of polarity). • Lipid bilayers have an extremely low permeability for ions and a low permeability for polar molecules capable of separation because they have strict control over permeability evolutionarily speaking, key is when membrane system form a searate biomolecule from outside phospholipid bilayer is semipermeable, allows certain ones in easy and prevents others. polarity and size and concentration determine permeability of a given molecule

There Are Three Common Types of Membrane Lipids

The common types of membrane lipids are as follows: - phospholipids - glycolipids - (critical to biological system) cholesterol- (special type of lipid that is very rigid, can cause heart attacks)

Archaeal Membranes Are Built from Ether Lipids With Branched Chains

The ether linkages and branching structure of membrane lipids of extremophiles prevent hydrolysis and oxidation of membranes in harsh environments. high/low pH or temp thermophiles more stable membrane to keep it stable under extreme conditions

The Fluid Mosaic Model Allows Lateral Movement but Not Rotation Through the Membrane

The fluid mosaic model describes membranes as twodimensional solutions of oriented lipids and globular proteins. • The lipids serve as a solvent and a permeability barrier. • Lipids rapidly diffuse laterally in membranes, although transverse diffusion (or flip-flopping) is very rare without the assistance of enzymes. • The prohibition of transverse diffusion accounts for the stability of membrane asymmetry not completely free flowing slide 53 along plane is easy and fast transverse diffusion is slower, very less strenght proteins differ in their rate of lateral diffusion, some quick others not, depends on function and whether or not its anchored to another structure phospholipids move quickly along the lateral direction because there arent any energy barrier that must be overocme. on the other hand, transverse diffusion is very difficult because during flip flop, polar head must travel through the nonpolar core of the membrane. this is energetically unfavorable, proteins is even more unfavorable suggesting they do not flip flop some but not all proteins move laterally, flippaeses needed to transverse diffusion

spontaneous formation of lipid bilayer

The hydrophobic effect is the major driving force in membrane formation the interaction of the hydrocarbon tails release water molecule from the nonpolar regions and this is energetically favorable. therefore, tails spontaneously aggregate to the interior of the membrane in addition the VDW forces between adjacent tails, the electric and H bonds between adjacent heads and the H bonds between the water and the head stabilize the membrane

All Biological Membranes are Asymmetric

The outer and inner leaflets (faces) of all biological membranes have different components and different enzymatic activities from each other. • Example: asymmetry of the Na+-K+ pump in the plasma membrane, needs to have orientation crrect to interact with ATP molecule. these proteins are placed into the membrane in an asymmetric fashion following their synthesis asymmetry is presevred because membrane proteins do not rotate from one site to another. and because membranes always arise and grow from existing molecules. lipids are also inserted asymmetrically but they can flipflop and therefore their asymmetry isnt absolute glycolipids and sphingolipids cab also lead to asymmetry different composition of lipids and proteins different in positioning and orientation of the membrane proteins difference in the enzymatic activities of the inner and outer surface

Proteins Carry Out Most Membrane Processes

While membrane lipids establish a permeability barrier to polar molecules and ions, membrane proteins allow transport of molecules and information across the membrane. • Membranes vary in protein content, from less than 20% to as much as 75%. • Membrane proteins can be visualized by SDSpolyacrylamide gel electrophoresis. • The types of membrane proteins in a cell are a reflection of the biochemistry occurring inside the cell.

SNARE Complexes Initiate Membrane Fusion

interact with producing fusion together, membrane compartments try to cut snares help slide 70

permeability of a given molecule across lipid bilayer

polarity: permeability of a molecule depends on ability to dissolve in nonpolar solution. There more nonpolar it is, the easier it moves through membrane, so charged/polar mlecules dont move across readily because 1. lose of strong interactions w water and 2. cannot form stabilizing interactions with nonpolar tails (uncharged indole moves about 1000x more than charged tryptophan) size and conc: Water is exception to polarity because it doesnt have full charge, high conc inside and out of cell and its small

Preparation of Glycine-containing Liposomes

slide 27 Lipid vesiceles can be formed by mixing a lipid solution into an aqueous solution and then sonicating the solution. sonication involved bombarding w sound waves. The energy carried by the sound waves disperses the lipids allowing them to spontaneously aggregate into bilayer membrane liposomes liposomes can be made to contain desired molecules within the internal aqueous compartment. for instance, if the aqueous solution is replaced with a solution containing AA's, the AA's can become trapped inside the liposomes during the sonication process then separate by gel filtration mixing proteins with detergents and then w/ phospholipids we can create liposomes with proteins embedded in the bilayer membrane

Experimental Arrangement for the Study of a Planar Bilayer Membrane

slide 28

Hydropathy Plot for Porin

slide 48 not one high region when barrel needs to be assembled to be inside membrane, alpha helix easy to predict need to use other way to plot porin

Lipid Rafts Are Highly Dynamic Complexes Formed Between Cholesterol and Specific Lipids

• Cholesterol can form complexes with sphingolipids, glycolipids, and some GPI-anchored proteins. • Such complexes, which concentrate in small, defined regions of the membrane, are called lipid rafts. • Lipid rafts help to moderate membrane fluidity and appear to function in signal transduction. less fluid, more resistant to phase transition large molecules are densly packed into a small region, flattens slope too much cholesterol clogs blood vessels cant have cholesterol free diet important for biological function