Chapter 9: Lipids and Biological Membranes

liposomes

A synthetic vesicle bounded by a single lipid bilayer. phospholipids closed, self-sealing solvent-filled vesicles that are bounded by only a single bilayer Liposomes serve as models of biological membranes and also hold promise as vehicles for drug delivery since they area absorbed by many cells through fusion with the plasma membrane.

Lipids perform 3 biological functions

1. Lipid molecules in the form of lipid bilayers are essential components of biological membranes. 2. Lipids containing hydrocarbon chains serve as energy stores. 3. Many intra- and intercellular signaling events involve lipid molecules

Ceramides ************

A sphingosine derivative with an acyl group attached to its amino group.

functions provided by phospholipid bilayers

- keeps an aquesous solution inside from mixing with the outside (different concentrations of stuff) - a flexible container, with deformations easy to perform - different components available to tune the physical and mechanical properties (rigidity, shape, charge) - inside surface is different from the outside surface - can anchor stuff in the surface to provide additional functions, most importantly to move molecules in and out - a place to store/bind/transport hydrophobic material

Note that the -ate ending of the name of the fatty acid becomes _____ in the fatty acid ester.

-oyl

Gangliosides

A ceramide whose head group is an oligosaccharide containing at least one sialic acid residue. Gangliosides are the most complex glycosphingolipids. They are ceramides with attached oligosaccharides that include at least one sialic acid residue. The structures of gangliosides GM1, GM2, and GM3, three of the hundreds that are known. Gangliosides are primarily components of cell-surface membranes and constitute a significant fraction (6%) of brain lipids. Gangliosides have considerable physiological and medical significance. Their complex carbohydrate head groups, which extend beyond the surfaces of cell membranes, act as specific receptors for certain pituitary glycoprotein hormones that regulate a number of important physiological functions. Gangliosides are also receptors for certain bacterial protein toxins such as cholera toxin. Gangliosides most likely have an important role in the growth and differentiation of tissues as well as in carcinogenesis. Disorders of ganglioside breakdown are responsible for several hereditary sphingolipid storage diseases, such as Tay-Sachs disease

Sphingolipids

A derivative of the C18 amino alcohol sphingosine. Sphingolipids include the ceramides, cerebrosides, and gangliosides. Sphingolipids with phosphate head groups are called sphingophospholipids. Sphingolipids, like glycerophospholipids, are a source of smaller lipids that have discrete signaling activity.

unsaturated

A fatty acid that contains at least one double bond in its hydrocarbon chain.

polyunsaturated

A fatty acid that contains more than one double bond in its hydrocarbon chain.

saturated fatty acids

A fatty acid that does not contain any double bonds in its hydrocarbon chain. highly flexible molecules that can assume a wide range of conformations because there is relatively free rotation around each of their C¬C bonds lowest energy confirmation is the fully extended conformation, which has the least amount of steric interference between neighboring methylene groups.

micelle

A globular aggregate of amphiphilic molecules in aqueous solution that are oriented such that polar segments form the surface of the aggregate and the nonpolar segments form a core that is out of contact with the solvent. Single-tailed amphiphiles, such as soap anions, form spheroidal or ellipsoidal micelles because of their tapered shapes (their hydrated head groups are wider than their tails;

Integral or intrinsic proteins

A membrane protein that is embedded in the lipid bilayer and can be separated from it only by treatment with agents that disrupt membranes. Integral proteins are amphiphiles; the protein segments immersed in a membrane's non polar interior have predominantly hydrophobic surface residues, whereas those portions that extend into the aqueous environment are by and large sheathed with polar residues.

oils

A mixture of triacylglycerols that is liquid at room temperature.

fats

A mixture of triacylglycerols that is solid at room temperature.

triacylglycerols (triglycerides) * pg 244

A nonpolar lipid in which three fatty acids are esterified to a glycerol backbone. Triacylglycerols function as energy reservoirs in animals and are therefore their most abundant class of lipids even though they are not components of cellular membranes. Triacylglycerols differ according to the identity and placement of their three fatty acid residues. are stored in anhydrous form

sterol

An alcohol derivative of a steroid.

Glycerophospholipids (or phosphoglycerides) * pg 245

An amphiphilic lipid in which two fatty acyl groups are attached to a glycerol-3-phosphate whose phosphate group is linked to a polar group. The major lipid components of biological membranes. They consist of glycerol-3-phosphate whose C1 and C2 positions are esterified with fatty acids. the phosphoryl group is linked to another usually polar group, X. Glycerophospholipids are therefore amphiphilic molecules with nonpolar aliphatic (hydrocarbon) "tails" and polar phosphoryl-X "heads." usually used for cellular membranes

protein kinase

An enzyme that catalyzes the transfer of a phosphoryl group from ATP to the OH group of a protein Ser, Thr, or Tyr residue.

phospholipases

An enzyme that hydrolyzes one or more bonds of a glycerophospholipid.

Lipids

Any member of a broad class of biological molecules that are largely or wholly hydrophobic and therefore tend to be insoluble in water but soluble in organic solvents such as hexane. Lipids (Greek: lipos, fat) are the fourth major group of molecules found in all cells. Unlike nucleic acids, proteins, and polysaccharides, lipids are not polymeric. However they do aggregate, and it is in this state that they perform their central function as the structural matrix of biological membranes. They are largely hydrophobic and only sparingly soluble in water Lipids are substances of biological origin that are soluble in organic solvents such as chloroform and methanol. Hence, they are easily separated from other biological materials by extraction into organic solvents. Fats, oils, certain vitamins and hormones, and most nonprotein membrane components are lipids.

Steroids

Any of numerous naturally occurring lipids composed of four fused rings; many are hormones that are derived from cholesterol. - composed of four fused cycloalkane rings - examples: cholesterol, estradiol, cortisone, testoserone, dexamethasone - differences are in what is attached to the rings and the oxidation state (mostly hydroxyl and carbonyl groups) - hundreds of different steroids are found in plants and animals.

lipid bilayer

Bilayer - An ordered, double layer of amphiphilic molecules in which polar segments point toward the two solvent-exposed surfaces and the nonpolar segments associate in the center. Lipid Bilayer - The two hydrocarbon tails of glycerophospholipids and sphingolipids give these amphiphiles a somewhat rectangular cross section. The steric requirements of packing such molecules together yields large dislike micelles that are really extended bimolecular leaflets.

Cerebrosides

Cerebrosides are ceramides with head groups that consist of a single sugar residue. These lipids are therefore glycosphingolipids. Galactocerebrosides and glucocerebrosides are the most prevalent. Cerebrosides, in contrast to phospholipids, lack phosphate groups and hence are nonionic.

cholesterol

Cholesterol modulates membrane permeabilty and fluidity by making the membrane brittle. Cholesterol is the most abundant steroid in animals, is further classified as a sterol because of its C3-OH group. Cholesterol is a major component of animal plasma membranes, typically constituting 30 to 40 mol % of plasma membrane lipids. Its polar OH group gives it a weak amphiphilic character, whereas its fused ring system provides it with greater rigidity than other membrane lipids. Cholesterol can also be esterified to long-chain fatty acids to form cholesteryl esters, such as cholesteryl stearate. Some cholesterol is good, but too much cholesterol is bad. A high level of serum cholesterol is an indicator for cardiovascular disease In mammals, cholesterol is the metabolic precursor of steroid hormones, substances that regulate a great variety of physiological functions Cholesterol, which by itself does not form a bilayer, decreases membrane fluidity because its rigid steroid ring system interferes with the motions of the fatty acid side chains in other membrane lipids. It also broadens the temperature range of the phase transition. This is because cholesterol inhibits the ordering of fatty acid side chains by fitting in between them. Thus, cholesterol functions as a kind of membrane plasticizer.

adipocytes

Fat cell, which is specialized for the synthesis and storage of triacylglycerols from free fatty acids.

Adipose tissue

Fat cells; distributed throughout an animal's body.

Bilayer formation is driven by what phenomenon

Hydrophobic Effect

What are the functions of membrane proteins

Membrane proteins catalyze chemical reactions, mediate the flow of nutrients and wastes across the membrane, and participate in relaying information about the extracellular environment to various intracellular components. Such proteins carry out their functions in association with the lipid bilayer. They must therefore interact to some degree with the hydrophobic core and/or the polar surface of the bilayer.

What are the most abundant sphingolipids

Sphingomyelins Cerebrosides Gangliosides

steroid hormone

Steroid hormones are classified according to the physiological responses they evoke: 1. The glucocorticoids, such as cortisol (a C21 compound), affect carbohydrate, protein, and lipid metabolism and influence a wide variety of other vital functions, including inflammatory reactions and the capacity to cope with stress. 2. Aldosterone and other mineralocorticoids regulate the excretion of salt and water by the kidneys. 3. The androgens and estrogens affect sexual development and function. Testosterone, a C19 compound, is the prototypic androgen (male sex hormone), whereas -estradiol, a C18 compound, is an estrogen (female sex hormone).

lung surfactant

The amphipathic protein and lipid mixture that prevents collapse of the lung alveoli (microscopic air spaces) on the expiration of air.

DO membranes of the Antarctic icefish (a nearly colorless fish that lacks hemoglobin and lives in -1.9C water) have loner and/or more saturated fatty acids compared to tropical fish?

The icefish has shorter fatty acyl chains and more unsaturated fatty acyl chains, compared to a tropical fish, in order to maintain membrane fluidity at the low temperatures at which it lives.

Sphingomyelins

The most common sphingolipids, are ceramides bearing either a phosphocholine or a phosphoethanolamine head group, so they can also be classified as sphingophospholipids. They typically make up 10 to 20 mol % of plasma membrane lipids. Although sphingomyelins differ chemically from phosphatidylcholine and phosphatidylethanolamine, their conformations and charge distributions are quite similar. The membranous myelin sheath that surrounds and electrically insulates many nerve cell axons is particularly rich in sphingomyelins. Sphingomyelin itself, as well as the ceramide portions of more complex sphingolipids, appear to specifically modulate the activities of protein kinases and protein phosphatases (enzymes that remove phosphoryl groups from proteins) that are involved in regulating cell growth and differentiation.

transverse diffusion / flip-flop

The movement of a lipid from one leaflet of a bilayer to the other. Is extremely rare. This is because a flip-flop requires the hydrated, polar head group of the lipid to pass through the anhydrous hydrocarbon core of the bilayer. Extremely slow rate (couple of days)

lateral diffusion

The movement of a lipid within one leaflet of a bilayer. Lipids are highly mobile in the plane of the bilayer. It has been estimated that lipids in a membrane can diffuse the 1-m length of a bacterial cell in 1 s. Because of the mobilities of the lipids, the lipid bilayer can be considered to be a two-dimensional fluid.

phosphatidic acids

The simplest glycerophospholipid, consisting of two fatty acyl groups attached to glycerol-3-phosphate. simplest form of glycerophospholipids, in which X = H are present in only small amounts in biological membranes

Quiz Question: What is the role of cholesterol when present in the lipid bilayer? a) incorporation into the membrane results in increased rigidity b) functions as a precursor to triglycerides c) is a transmembrane protein d) is synthesized from steroid hormones e) all of the above

a) incorporation into the membrane results in increased rigidity

fatty acids

carboxylic acids with long-chain hydrocarbon side groups In higher plants and animals, the predominant fatty acid residues are those of the C16 and C18 species: palmitic, oleic, linoleic, and stearic acids.

How can we tell that there is motion in the phospholipid bilayer

cell fusion

Fatty acid double bonds almost always have the ___ configuration

cis This puts a rigid 30° bend in the hydrocarbon chain.

Which of the following is comprised primarily of fatty acids and other single tailed molecules that possess both non-polar and polar properties? a) lipid bilayers b) two-dimensional membranes c) liposomes d) micelles e) solvent-filled vesicles

d) micelles

Two important classes of polyunsaturated fatty acids are designated as ___________ or __________ fatty acids. a) omega-4 or omega-6 b) omega-3 or omega-5 c) omega-2 or omega-7 d) omega-3 or omega06

d) omega-3 or omega-6 a nomenclature that identifies the last double-bonded carbon atom as counted from the methyl terminal (omega) end of the chain Examples: alpha-Linolenic acid (omega 3) and linoleic acid (omega-6)

Unsaturated fatty acids pack together less efficiently than saturated acids. The reduced van der Waals interactions of unsaturated fatty acids cause their melting points to ________ with the degree of unsaturation.

decrease. More double bonds the unsaturated fat has, the lower the melting point of the fat is

Integral membrane proteins: different details of structure =

different function

The properties of fatty acids depend on their _______

hydrocarbon chains

The fluidity of the unsaturated fatty acid ________ with the degree of unsaturation of the fatty acid

increase More double bonds the unsaturated fat has, the more fluid the fat is

The transfer of a lipid molecule across a bilayer by ______ or ______

lateral diffusion transverse diffusion / flip-flop

Fats are a highly efficient form in which to store ________

metabolic energy

Melting point of saturated fatty acids increases with increasing _______________

molecular weight

What else do biological membranes contain other than lipids?

peripheral protein, oligosaccharide, integral protein, cholesterol, hydrophobic alpha-helix, lipid-linked protein biological membranes also have directionality

The Fluidity of a Lipid Bilayer Is ________-Dependent.

temperature As a lipid bilayer cools below a characteristic transition temperature, it undergoes a sort of phase change in which it becomes a gel-like solid; that is, it loses its fluidity The transition temperature of a bilayer increases with the chain length and the degree of saturation of its component fatty acid residues for the same reasons that the melting points of fatty acids increase with these quantities.

In polyunsaturated fatty acids, the double bonds tend to occur at every _____ carbon atom so that they are not conjugated

third

Triacylglycerols contain what esterified fatty acids?

three glycerols

Over half of the fatty acid residues of plant and animal lipids are _______ and are often _________________

unsaturated; polyunsaturated