Basic Biochemistry CLS 233 1st semester, 2014- 2015 Ch:10 Lipids

Storage Lipids The fats and oils used almost universally as stored forms of energy in living organisms are derivatives of fatty acids.

Fatty Acids Are Hydrocarbon Derivatives Fatty acids are carboxylic acids with hydrocarbon chain ranging from 4 to 36 carbons long (C4 to C36). In some fatty acids, this chain is unbranched and fully saturated (contains no double bonds); in others the chain contains one or more double bonds (Table 10–1).

Nomenclature of fatty acids A simplified nomenclature for these compounds specifies the chain length and number of double bonds, separated by a colon; for example, the 16-carbon saturated palmitic acid is abbreviated 16:0, and the 18-carbon oleic acid, with one double bond, is 18:1. The positions of any double bonds are specified by superscript numbers following Δ (delta); a 20-carbon fatty acid with one double bond between C-9 and C-10 (C-1 being the carboxyl carbon) and another between C-12 and C-13 is designated 20:2(Δ 9,12).

Properties of F.A. The physical properties of the fatty acids, are largely determined by the length and degree of unsaturation of the hydrocarbon chain. The nonpolar hydrocarbon chain accounts for the poor solubility of fatty acids in water. The longer the fatty acyl chain and the fewer the double bonds, the lower is the solubility in water. The carboxylic acid group is polar (and ionized at neutral pH) and accounts for the slight solubility of short-chain fatty acids in water.

Properties of F.A. At room temperature (25 C), the saturated fatty acids from 12:0 to 24:0 have a waxy consistency, whereas unsaturated fatty acids of these lengths are oily liquids. This difference in melting points is due to different degrees of packing of the fatty acid molecules (Fig. 10–1). In the fully saturated compounds, molecules can pack together tightly in nearly crystalline arrays. In unsaturated fatty acids, a cis double bond forces a kink in the hydrocarbon chain.

Triacylglycerols Are Fatty Acid Esters of Glycerol Triacylglycerols are composed of three fatty acids each in ester linkage with a single glycerol (Fig. 10–2). Most naturally occurring triacylglycerols are mixed; they contain two or more different fatty acids. Because the polar hydroxyls of glycerol and the polar carboxylates of the fatty acids are bound in ester linkages, triacylglycerols are nonpolar, hydrophobic molecules, essentially insoluble in water.

Triacylglycerols Provide Stored Energy and Insulation There are two significant advantages to using triacylglycerols as stored fuels, rather than polysaccharides such as glycogen and starch: 1- Because Oxidation of triacylglycerols yields more than twice as much energy, gram for gram, as the oxidation of carbohydrates . 2- Because triacylglycerols are hydrophobic and therefore unhydrated, the organism that carries fat as fuel does not have to carry the extra weight of water of hydration that is associated with stored polysaccharides In some animals, triacylglycerols stored under the skin serve not only as energy stores but as insulation against low temperatures.

Many Foods Contain Triacylglycerols - Vegetable oils such as corn (maize) and olive oil are composed largely of triacylglycerols with unsaturated fatty acids and thus are liquids at room temperature . Triacylglycerols containing only saturated fatty acids, such as tristearin, the major component of beef fat, are white, greasy solids at room temperature. Note: When lipid-rich foods are exposed too long to the oxygen in air, they may spoil and become rancid. The unpleasant taste and smell associated with rancidity result from the oxidative cleavage of the double bonds .

PART 2

Structural Lipids in Membranes Biological membranes is a double layer of lipids, which acts as a barrier to the passage of polar molecules and ions. Membrane lipids are amphipathic: one end of the molecule is hydrophobic, the other hydrophilic. Their hydrophobic interactions with each other and their hydrophilic interactions with water direct their packing into sheets called membrane bilayers.

Structural Lipids in Membranes

L-glycerol 3-phosphate: The backbone of phospholipids Glycerol is pro-chiral, it has no asymetric carbons, but attachment of phosphate to either end makes it chiral.

Glycerophospholipids 1. The common glycerophospholipids are diacylglycerols linked to head-group alcohols through a phosphodiester bond.

Glycerophospholipids Phosphatidic acid, is the parent compound (X=H).

Glycerophospholipids Each derivative is named for the head-group alcohol (X) with the pre-fix "phosphatidyl-".

Each derivative is named for the head-group alcohol (X) with the pre-fix "phosphatidyl-".

In caridiolipin, two phosphatidic acids share a single glycerol, hence it is also called diphosphatidly-glycerol.

Glycerophospholipids 2. The fatty acids can vary greatly between organisms, tissues and cells. In general, they contain a saturated C16 or C18 fatty acid at C1 and a C18 to C20 unsaturated fatty acid at C2. Saturated with protons.

Glycerophospholipids 3. Common components of cell membranes.

Structures of some common glycerophospholipids (lecithin) How to recognize the strucures, rather than memorizing: look for : serine is only amino acid, look for alpha amino and carboxyl group. Ethanolamine is the only amine not an amino acid. Inositol is the only one with an inositol ring. Cardiolipin is easy since it has two glycerol backbones. That leave choline by default.

Some phospholipids have ether linked fatty acids Plasmalogens have an ether-linked alkenyl chain where most glycerophospholipids have an ester-linked fatty acid. The head group alcohol is choline. ~50% of the heart phospholipids are plasmalogens. ETHER ESTER Vetebrate heart tissue is uniquely enriched in ether lipids, about half of the phospholipids are plamalogens. ?perhaps resistance to phospholipases?

Notes Plasmalogens: When the fatty acid at carbon 1 of a glycerophospholipid is replaced by an unsaturated alkyl group attached by an ether (rather than by an ester) linkage to the core glycerol molecule, a plasmalogen is produced.

Platelet-activating factor has a long ether-linked alkyl chain at C1 Platelet-activating factor has a long ether-linked alkyl chain at C1. Acetic acid is ester-linked at C2, which makes it more water soluble than most glycerophospholipids. The head-group alcohol is choline.

Platelet-activating factor is a potent molecular signal released from leucocytes that stimulates platelet aggregation. It also has a variety of effects on many tissues including roles in inflammation and the allergic response.

The principle classes of storage and membrane lipids Point out difference in 3rd position, fatty acid versus phosphate, phosphate versus sugar. All these lipids have either glycerol or sphingosine as the backbone. A third class of membrane lipids, the sterols, are discussed separately.

SPHINGOLIPIDS The 3-carbon backbone is analogous to the 3-carbons of glycerol. At C3 there is the long chain amino alcohol sphingosine.

SPHINGOLIPIDS At C2 there is a fatty acid which is usually saturated or monounsaturated, and can be either 16,18, 22, or 24 carbons long.

SPHINGOLIPIDS Ceramide is the parent compound. Other polar head groups can be attached at position X.

SPHINGOLIPIDS Glycosphingolipids are a sub-group of sphingolipids that contain sachharide headgroups

Sphingolipids at cell surfaces are sites of biological recognition 1. In humans at least 60 different sphingolipids have been identified. 2. Very prominent in neuronal plasma membranes. Carbohydrate moieties of sphingolipids define the human blood groups.

Glycosphingolipids as determinants of blood groups The human blood groups (O, A, B) are determined in part by the oligosaccharide head groups of these glycosphingolipids. Glc:D-glucose Gal:D-galactose GalNAc:N-acetyl-D-galactosamine Fuc:fucose

Phospholipids and sphingolipids are degraded in lysosomes

1. For each hydrolyzable bond in a glycerophospholipid there is a specific hydrolytic enzyme in the lysosome.

2. Phospholipase A1 hydrolyzes the fatty acid at C1.

3. Phospholipase A2 hydrolyzes the fatty acid at C2.

4. When one fatty acid is removed from either C1 or C2, a lysophospholipase removes the remaining fatty acid.

5. Phospholipases C and D each split one specific phosphodiester bond in the head group.

Working with Lipids Because lipids are insoluble in water, their extraction and subsequent fractionation require the use of organic solvents and some techniques not commonly used in the purification of water-soluble molecules such as proteins and carbohydrates Complex mixtures of lipids are separated by differences in the polarity or solubility of the components in nonpolar solvents. Lipids that contain ester or amide linked fatty acids can be hydrolyzed by treatment with acid or alkali or with highly specific hydrolytic enzymes (phospholipases, glycosidases) to yield their component parts for analysis. Some methods commonly used in lipid analysis are shown in Figure 10–23

Lipid Extraction Requires Organic Solvents Neutral lipids (triacylglycerols, waxes, pigments, and so forth) are readily extracted from tissues with ethyl ether, chloroform, or benzene. Membrane lipids are more effectively extracted by more polar organic solvents, such as ethanol or methanol. A commonly used extractant is a mixture of chloroform, methanol, and water, initially in volume proportions (1:2:0.8) that are miscible, producing a single phase. After tissue is homogenized in this solvent to extract all lipids, more water is added to the resulting extract and the mixture separates into two phases, methanol/water (top phase) and chloroform (bottom phase). The lipids remain in the chloroform layer, and more polar molecules such as proteins and sugars partition into the methanol/water layer.