Lipids - Marquette University1. Describe the structural differences between fats and oils. 2. Describe the structural differences between saturated, monounsaturated, polyunsaturated,

The Lipids

Objectives: I. Identify the differences between saponifiable and nonsaponifiable lipids. II. Identify the chemical composition and chemical properties of the precursors to the saponifiable

lipids (the products of saponification): A. The fatty acids.

1. The 14 most common fatty acids a) saturated b) monounsaturated c) polyunsaturated d) slightly amphipathic molecules

2. Some “uncommon” unsaturated fatty acids a) “bad” trans fatty acids b) “good” trans fatty acids

B. The polar alcohols - glycerol, serine, ethanolamine, choline, and inositol. C. Sphingosine.

1. amphipathic molecule D. Monosaccharides and modified monosaccharides. E. Long chain alcohols and vinyl alcohols.

1. structural & functional differences. III. Be familiar with the physical properties, chemical properties, and biological functions of each of

the families of saponifiable lipids. A. Describe the general structure and function of the waxes. B. Describe the general structures and functions of the triacylglycerols (simple lipids or neutral

lipids). 1. Describe the structural differences between fats and oils. 2. Describe the structural differences between saturated, monounsaturated, polyunsaturated,

and “trans” fats. C. Describe the general structures and functions of the phosphoglycerides.

1. Distinguish between simple and complex (compound) lipids. 2. Typical fatty acid content of the phosphoglycerides 3. What is the distinguishing characteristic or component of each of the different classes of

phosphoglycerides. 4. Distinguish between the hydrophilic “head” and hydrophobic “tail” of these amphipathic

lipids. D. Describe the general structures and functions of the ether lipids.

1. What is the distinguishing characteristic or component of the plasmalogens. E. Describe the general structures and functions of the sphingolipids.

1. Recognize the structural and functional differences among the ceramides, the sphingomyelins, the cerebrosides, and the gangliosides.

2. Distinguish between the hydrophilic “head” and hydrophobic “tail” of these amphipathic lipids.

F. From a given set of components identify which of the various triacylglycerols, phosphoglycerides, and/or sphingolipids is/are present and describe the general structures and

©Kevin R. Siebenlist, 20191

functions of the molecule. IV. Describe the function and specificity of the Phospholipases. V. Be familiar with the physical properties, chemical properties, and biological functions of each of

the families of nonsaponifiable lipids. A. Understand the structural features (isoprenes) and functions of the fat soluble vitamins. B. Understand the structures and functions of the eicosanoids in physiological processes.

1. Know the terms eicosanoids, prostaglandins, leukotrienes, and thromboxanes. 2. Know the lipid from which prostaglandins, leukotrienes, and thromboxanes are produced. 3. State at least six known physiological effects of the eicosanoids. 4. Know how aspirin reduces pain.

C. Identify the common structural features of steroids and relate them to the other isoprenes. 1. Be familiar with the precursor / product relationships and functions of the various steroid

hormones and vitamin D.

Background

The amino acids, carbohydrates, and nucleotides can all be defined on the basis of the organic functional groups on the molecule or the component parts that make up the molecule. Amino acids all contain a carboxylic acid group and an α amino group. Carbohydrates are polyhydroxyl aldehydes or polyhydroxyl ketones or molecules that yield polyhydroxyl aldehydes or polyhydroxyl ketones upon hydrolysis. Nucleotides contain a heterocyclic base, an aldopentose, and one or more phosphates.

Lipids are defined based upon their physical properties. They are the cellular constituents that are, at best, slightly water soluble. Lipids are soluble in non-polar organic solvents. These water insoluble molecules are either non-polar or AMPHIPATHIC. Amphipathic molecules contain a strongly polar region and a strongly non-polar region.

The lipids can be divided into two major groups based on their reactivity with hot sodium hydroxide or hot potassium hydroxide solutions. The SAPONIFIABLE LIPIDS react with hot alkali solutions to form soaps. SAPONIFICATION is from the latin meaning SOAP FORMING. Soaps are the Na+ or K+ salts of fatty acids, and these salts are more water soluble that the uncharged fatty acids. Aqueous strong bases hydrolyze ester, amide, and glycosidic bonds resulting in the formation of carboxylic acids, aldehydes, ketones, alcohols, and amines. Therefore, the saponifiable lipids are complex, water insoluble molecules made up from smaller molecules covalently joined by one or more ester, amide, or glycosidic bond. NONSAPONIFIABLE lipids do not react with hot NaOH or KOH. They do not contain bonds that can be hydrolyzed by aqueous strong bases. Nonsaponifiable lipids are single large hydrophobic molecules.

Before the saponifiable lipids are discussed, the small molecules that comprise the saponifiable lipids will be examined. These small molecules are the precursors of the saponifiable lipids. They are combined in a variety ways to form the various classes of saponifiable lipids. The precursors of the saponifiable lipids are:

1. FATTY ACIDS are the most abundant precursors of the saponifiable lipids. At least one fatty acid is present in all of the saponifiable lipids. The fatty acids are monocarboxylic acids containing from 8-36 carbon atoms. The majority of naturally occurring fatty acids contain an even number of carbon atoms.


H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Laurate (Lauric Acid) - 12 carbons, 0 double bonds - 12:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Myristate (Myristic Acid) - 14 carbons, 0 double bonds - 14:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Palmitate (Palmitic Acid) - 16 carbons, 0 double bonds - 16:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Stearate (Stearic Acid) - 18 carbons, 0 double bonds - 18:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Arachidate (Arachidic Acid) - 20 carbons, 0 double bonds - 20:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Caprate (Capric Acid) - 10 carbons, 0 double bonds - 10:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Lignocerate (Lignoceric Acid) - 24 carbons, 0 double bonds - 24:0

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

Cerotate (Cerotic Acid) - 26 carbons, 0 double bonds - 26:0 ©Kevin R. Siebenlist, 20193

H3CCH2

H2CCH2

H2CCH2

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

H

H

Palmitoleate(Palmitoleic Acid)

16 carbons, 1 double bondbetween C9 & C10 - 16:1 9

H3CCH2

H2CCH2

H2CCH2

H2CCH2

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

OH

H

Oleate(Oleic Acid)

18 carbons, 1 double bondbetween C9 & C10 - 18:1 9

CH2

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

O

H

H

C

CCH2H

H

H2CCH2

H2CCH3

Linoleate (Linoleic Acid)18 carbons, 2 double bonds

between C9 & C10 and C12 & C13 - 18:2 9,12

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

OH

H

CH2C

CCH2C

C

H2C

CH3

H

H

H

H

-Linolenate (Linolenic Acid)18 carbons, 3 double bonds between

C9 & C10, C12 & C13, and C15 & C16 - 18:3 9,12,15


Fatty acids can be SATURATED (no carbon-carbon double bonds), MONOUNSATURATED (one carbon-carbon double bond in the molecule) or, POLYUNSATURATED (two or more carbon-carbon double bonds in the molecule). The double bonds in the majority of the naturally occurring fatty acids are in the “cis” configuration. In the polyunsaturated fatty acids the double bonds are rarely conjugated, they are usually separated by a methylene (-CH2-) group. The polyunsaturated fatty acids LINOLEATE and α-LINOLENATE are essential fatty acids. They must be present in the human diet and the human animal must ingest adequate amounts to maintain the “normal state”. The human animal cannot synthesize these fatty acids. When counting from the methyl end of the molecule, linoleate is “the” Ω-6 fatty acid and α-linolenate is “the” Ω-3 fatty acid. These two fatty acids are the precursors of the other Ω-6 and Ω-3 fatty acids needed by the human animal. For example, LINOLEATE is the precursor for arachidonate and arachidonate is the precursor for a group of nonsaponifiable lipids called The Eicosanoids. α-LINOLENATE is the precursor for Docosahexaenoate (DHA) and Eicosapentaenoate (EPA). DHA is the most abundant omega-3 fatty acid in the brain and retina.

C

CCH2

CC

CH2

H2C

CH2

H2C

CO

O

H

H

CH2C

C

H2C

CH2

H2C

CH2

CH3H

H

H

H

γ-Linolenate (Linolenic Acid)18 carbons, 3 double bonds between

C6 & C7, C9 & C10, and C12 & C13 - 18:3Δ6,9,12

CCH2

H2C

CH2

CC

CH2

H

H

C

CCH2H

H

CC

H2C

H

H CC

H

H

H2C

H2C

O

O

CH2

H2C

CH3

Arachidonate (Arachidonic Acid)20 carbons, 4 double bonds between

C5 & C6, C8 & C9, C11 & C12, and C14 & C15 - 20:4Δ5,8,11,14


Fifty percent of the weight of a neuron's plasma membrane is composed of DHA. EPA functions to lower inflammation.

Fatty acids at physiological pH are anions, the carboxylic acid groups has donated its proton to some base. The smaller fatty acids when in the anionic form are slightly soluble. Solubility decreases as the number of carbon atoms increase. Their melting and boiling points increase as the number of carbon atoms increase. With a fixed number of carbon atoms, the melting and boiling points decrease as the number of double bonds increase. “Cis” double bonds causes “kinks” in the molecule making it difficult for the unsaturated fatty acids to pack into a “crystalline” matrix.

2. SMALL POLAR ALCOHOLS such as glycerol (1,2,3-propanetriol), the amino acid serine, ethanolamine, choline, and inositol. Ethanolamine is formed by the decarboxylation of serine. Choline is N,N,N-trimethylethanolamine. Inositol is a six carbon cyclic polyalcohol. Glycerol is the second most abundant precursor of the saponifiable lipids.

CH2C

C

CH2C

C

CH2C

C

CH2C

C

CH2C

C

CH2C

CCH2

CH3

H2CC

OH

OH

H

H

H

H

H

H

H

H

H

HH

C

CH2H2C

H2C

CCH2C

CC

CH2

CC

CH2CC

H2C CC

CH2H3COH

O

H

H

HH

HH

H

H H

H

H2CCH

H2C

OH

OH

OHGlycerol

Ethanolamine

HOCH2

H2C

NH3

Serine

HO

H2C

CHC

O

O

NH3

Choline

HO

H2C

CH2

N

CH2

CH3

CH3

OH C

C

C C

C

C

H

H

OH

OH

HOH

H

OHOH

H H

Inositol


3. SPHINGOSINE is an 18 carbon amphipathic molecule. The first three carbons contain polar groups. There are hydroxyl groups on carbons one and three and a polar amine group on carbon two. The remaining 15 carbons (4 through 18) are non-polar hydrocarbons. There is a “trans” double bond between carbon 4 and 5.

4. PHOSPHATE

5. MONOSACCHARIDES and MODIFIED MONOSACCHARIDES

6. LONG CHAIN ALCOHOLS are 8 to 40 carbon atoms long and contain a single hydroxyl group on carbon one. A proportion of the alcohols present in the saponifiable lipids are VINYL ALCOHOLS. The Vinyl Alcohols found in lipids are are 8 to 40 carbon atoms long, contain a C-1 hydroxyl group, and a carbon-carbon double bond between C-1 and C-2.

YZ YZ YZ YZ YZ YZ YZ YZ YZ YZ YZ

Sphingosine

HO

H2C

CHCH

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3

NH3

OH

HO

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3

HO

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3

HOHC

CH

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3

HOHC

CH

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3


The WAXES

The WAXES are the simplest class of saponifiable lipids. They are composed of a long chain fatty acid (14 to 36 carbons) in ester linkage to a long chain alcohol (16 to 40 carbons). Waxes form a waterproof coating on the leaves, fruits, and seeds of plants and on the skin, furs, and feathers of aquatic and marine animals.

Saponifiable Lipids

Waxes Glycerol Lipids Sphingolipids

Triacylglycerols Phosphoglycerides Ether Lipids(Plasmalogens)

Sphingomyelins Glycosphingolipids

CerebrosidesGangliosides Globosides

O

O

O

O

O

O

Spermaceti CH3(CH2)14COO(CH2)15CH3

Beeswax CH3(CH2)24COO(CH2)29CH3

Carnuba Wax CH3(CH2)30COO(CH2)33CH3


The TRIACYLGLYCEROLS The TRIACYLGLYCEROLS are also called the SIMPLE LIPIDS or the NEUTRAL LIPIDS. Triacylglycerols are composed of three fatty acids in ester linkage to a molecule of glycerol. Any combination of the fatty acids (depicted above) and/or any of the other (larger or smaller) fatty acids can be esterified to glycerol in the triacylglycerols. These molecules are very non-polar and electrically neutral. Triacylglycerols serve three functions. They are the major energy storage molecule in animals for two reasons. First, in biological systems energy is released by oxidation reactions. Since the majority of the mass of a triacylglycerol is hydrocarbon, the most reduced form of organic carbon, a large amount of energy is released when they are completely oxidized to CO2 and H2O. Second, since they are strongly hydrophobic, they can be stored in the cell as an “oil droplet” with little if any associated water. When carbohydrates are stored as starch or glycogen each sugar monomer carries along several hydrogen bonded H2O molecules. These hydrogen bonded H2O molecules take up storage space. On a gram per gram basis more triacylglycerol can be stored in a given volume because no water needs to be stored with it. The triacylglycerols are also insulators against heat loss (second function) and they are shock absorbers against trauma (third function).

H2C

HC

H2C

O

O

CH3CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CO

O CH3CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

CH3CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

O

H2C

CH

H2C

O

O CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

CH3H2C

CH2H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O H

H

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O


When a monounsaturated and / or a polyunsaturated triacylglycerol is partially hydrogenated, saturated and / or “TRANS FATS” result. “TRANS FATS” have been deemed unfit for human consumption. “TRANS FATS” are formed when the double bonds of unsaturated fatty acids in polyunsaturated triacylglycerols (see below) are reduced with a less than stoichiometric amount of H2 (partially hydrogenated). The conditions of this industrial reaction reduces some of the double bonds in the unsaturated fatty acids to single bonds. However, since there is a limiting amount of H2 some of the double bonds, rather than undergoing reduction, undergo a change in configuration from cis to trans. The three trans fatty acids most often found in “TRANS FATS” are depicted below. Note: these fatty acids are the trans isomers of the naturally occurring cis forms.

H2CCH

H2C

O

CH3CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CO

O

CH3H2C

CH2H2C

CH2H2C

CH2H2C

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O H

H

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

H

H

H2CC

CH2C

CC

CH2

H3C

H

H

H

H

H2CCH

H2C

O

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

H

H

CH3CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

OCH3

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O


Not all fatty acids with trans double bonds are harmful to human health. A variety of naturally occurring fatty acids containing trans double bonds have been identified and have been shown to be beneficial for human health. These naturally occurring “good” trans fatty acids make up only small percentage of the fatty acids, they are all polyunsaturated, and the double bonds are conjugated.

H2CCH

H2C

O

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

H

H

CH3CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

OCH3

CH2

H2C

CH2

H2C

CC

CH2

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O H

H H

H

H3C

H2C

CH2

H2C

CH2

H2C

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

H

H

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

H

H

H3C

H2C

CH2

H2C

CH2

CC

H2C

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

OH

HH

H


H3CCH2

H2CCH2

H2CCH2C

C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CO

O

HH

H

H

H3C

H2C

CH2

H2C

CC

CC

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

HH

H

H

H

H

H3C

H2C

CC

CC

CC

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

O

H

HH

H

H

HH

H

H3C

H2C CH2

H2C CH2

C CC C

C CC C

H2C CC

H2CCH2

H2CC O

O

H

H

HHH

HH

HHH


The remaining saponifiable lipids are termed the COMPLEX LIPIDS since they are composed of more and different subunits. They have a more complex structure and most of them are amphipathic.

The PHOSPHOGLYCERIDES

The PHOSPHOGLYCERIDES are the first group of complex lipids. The simplest phosphoglyceride is PHOSPHATIDATE (PHOSPHATIDIC ACID is the un-ionized form). This molecule contains two fatty acids in ester linkage to the hydroxyl groups on carbon 1 and 2 of glycerol. A molecule of phosphate is in ester linkage to the hydroxyl group on carbon 3 of glycerol. The presence of phosphate makes this molecule AMPHIPATHIC; it has a polar region (a polar head), the phosphate group, and a non-polar region (a non-polar tail), the two fatty acids.

The cell contains very little phosphatidate. Phosphatidate is the precursor for the other, more abundant phosphoglycerides. These more abundant phosphoglycerides contain one of the polar alcohols in ester linkage to the phosphate group of phosphatidate. The addition of these alcohol molecules to phosphatidate increases the polarity of the polar region of the molecule. These lipids are more amphipathic than phosphatidate.

PHOSPHATIDYLCHOLINE is formed when a molecule of choline is esterified to the phosphate of phosphatidate. Phosphatidylcholine is sold in health food stores as LECITHIN.

PHOSPHATIDYLETHANOLAMINE is formed when ethanolamine is esterified to the phosphate.

O

H2C

CH

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

CH3H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

H

H

PO

O

OPhosphatidate

Phosphatidylcholine(Lecithin)

CH2

HC

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

CH3H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

H

H

H2C

H2C

N CH3CH3

H3C

OPO

O

O


PHOSPHATIDYLSERINE is made by attaching the side chain hydroxyl group of the amino acid serine to phosphatidate.

PHOSPHATIDYLINOSITOL is formed by adding inositol.

PHOSPHATIDYLGLYCEROL is formed when a second molecule of glycerol is attached.

C

H2C

O

CH2

H2C

CC

H2C

H

H

CC

H2C

H

H

CC

H2C

H

H

CC

H

H

H2CCH2

H2C

CH2

CH3

CH2

CH

H2C

O CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

H2C

H2C

NH3O

OPO

O

O

Phosphatidylethanolamine

CH2

CH

H2C

O

O

H2CH

C

NH3

H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O H

H

CC

H2C

H

H

CH2

H2C

CH2

CH3

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

C

O

O

OPO

O

O

Phosphatidylserine

CH2

CH

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

CH3H2C

CH2H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O H

H

O OP

O

OHC

C

CC

C

C

H

H

OH

H OH

H

OH OH

HH

OPhosphatidylinositol


DIPHOSPHATIDYLGLYCEROL or CARDIOLIPIN is two molecules of phosphatidate joined / bridged by a third molecule of glycerol. CARDIOLIPIN was first isolated from heart muscle, hence its name. However, the name is incorrect in that this lipid is a major component of mitochondrial membranes rather than cardiac muscle membranes. It is found in high concentrations in the heart because the heart contains one of the highest concentrations of mitochondria.

Any combination of fatty acids (from 8 to 36 carbons) can be found in the phosphoglycerides of cellular membranes. Most often a C16 or C18 saturated fatty acid is esterified to carbon one of glycerol and a C18 or C20 unsaturated fatty acid is attached at carbon two.

PhosphatidylglycerolCH2

HC

H2C

O

O

H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O H

H

CC

H2C

H

H

CH2

H2C

CH2

CH3

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

OPO

O

OCH2

CH C

H2

HOOH

O

H2C

CH

H2C

O

O

H3CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CC O

CH3

CH2H2C

CH2H2C

CH2CCCH2

H2CCH2

H2CCH2

H2CCH2

CO

H

H

P

O

O

O

O

H2C

CH

H2C

O

O

CH3

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

H2CCH2

CO

H3C

H2C CH2

H2C CH2

H2C CC

H2CCH2

H2CCH2

H2CCH2

H2CC O

H

H

P

O

O

O

CH2

CHCH2

OH

Diphosphatidylglycerol(Cardiolipin)


The Phosphoglycerides are also called the GLYCEROPHOSPHOLIPIDS. Phosphoglycerides are major components of CELLULAR MEMBRANES, the plasma membrane that encloses the cell as well as the membranes that surround the subcellular organelles. As will be seen shortly, the amphipathic nature of these molecules makes then perfect for this function.

The ETHER LIPIDS The ETHER LIPIDS contain a long chain alcohol bonded to the hydroxyl group on C-1 of glycerol by an ether bond. Ether lipids are synthesized from phosphatidylcholine or phosphatidylethanolamine by a exchange reaction. The fatty acid on carbon one is exchanged for a long chain alcohol or a long chain vinyl alcohol forming the ether bond. Since the precursors are phosphatidylcholine or phosphatidylethanolamine polar alcohols present on the ether lipids are choline or ethanolamine.

PLATELET ACTIVATING FACTOR (see above) is an important ether lipid and a potent molecular signal. It is composed of 1-octadecanol in ether linkage to the hydroxyl group on C-1 of glycerol, ethanoate (acetate) in ester linkage to the hydroxyl group on C-2 of glycerol, and phosphocholine in ester linkage to the hydroxyl group on C-3. It is released from basophils and stimulates platelet aggregation and the release of serotonin, a vasoconstrictor, from platelets.

O

H2C

CH

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

H

H

PO

O

OCH2

H2CN

CH3H3C

CH3

Ether Lipid

O

H2C

CH

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH3C

O

PO

O

OCH2

H2CN

CH3H3C

CH3

Platelet Activating Factor


PLASMALOGENS are a subset of the ether lipids. All Plasmalogens contain a vinyl alcohol attached to carbon 1 of glycerol by a vinyl ether linkage and a choline molecule attached to the phosphate by an ester linkage. The human heart is particularly rich in Ether Lipids. About 50% of the membrane lipids of heart muscle are Ether Lipids or Plasmalogens.

The SPHINGOLIPIDS The SPHINGOLIPIDS make up the remaining group of saponifiable lipids. These lipids do not contain glycerol as part of the molecule, rather the backbone of the molecule is SPHINGOSINE. The sphingolipids, like the phosphoglycerides and the plasmalogens, are amphipathic and important components of cellular membranes. While the phosphoglycerides are found in all the membranes of the cell, the sphingolipids are found primarily in the plasma (cell) membrane.

CERAMIDE is the simplest sphingolipid. Ceramide is composed of a fatty acid in amide linkage to the amine group on carbon two of sphingosine. Ceramide is amphipathic. The hydroxyl groups on C-1 and C-3 and the amide group on C-2 of ceramide are the polar head and the fatty acid along with the last 15 carbons of sphingosine is the non-polar tail. Phosphoglycerides, plasmalogens, and the other sphingolipids are more amphipathic because they contain phosphate and other strongly polar molecules. The other sphingolipids are modification of or additions to ceramide.

SPHINGOMYELINS contain a phosphate group in ester linkage to C-1 of the sphingosine moiety of

O

H2C

CH

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH

HC

CH3H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

H

H

PO

O

OCH2

H2CN

CH3H3C

CH3

Plasmalogen

H2C

CHCH

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

H3C OH

NH

OH

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

H

H

CH2C

C

CH2C

C

CH2H3C

H

H

H

HCeramide


ceramide. A choline molecule is usually esterified to the phosphate. On occasion ethanolamine can be found linked to the phosphate.

The Phosphoglycerides, Plasmalogens, and Sphingomyelins are, as a group, called the PHOSPHOLIPIDS since they all these lipids contain PO4–3

GLYCOSPHINGOLIPIDS as a group contain sugar (glycos) molecules attached to the sphingosine. Three types of molecules, the CEREBROSIDES, the GLOBOSIDES, and the GANGLIOSIDES fall into this subgroup.

CEREBROSIDES contain a single monosaccharide in glycosidic linkage to the hydroxyl group on C-1 of ceramide. The attached monosaccharide is glucose or galactose. The resulting molecules are glucocerebrosides or galactocerebrosides.

GLOBOSIDES contain from two to five sugar residues in glycosidic linkage to the hydroxyl group on C-1 of ceramide. The sugars can be any combination of glucose, galactose, and/or N-acetylgalactosamine

H2C

CHCH

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

H3C O

NH

OH

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

H

H

CH2C

C

CH2C

C

CH2H3C

H

H

H

H

P

O

O

O

H2C CH2N

CH3

CH3

H3C

Sphingomyelin

OHO

OOH

OH

H2COH

H2C

CHCH

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

H3C

NH

OH

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

H

H

CH2C

C

CH2

H2C

CH2

H

H

H2C

H3CCerebroside

Globoside

H2CH

CCHC

H

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

H3C

HN

OH

CC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

CO

H

H

CH2C

C

CH2

H2C

CH2

H

H

H2C

H3C

C

C

CC

C

O

O

O

OH

OH

CH2OH

C

C

CC

C

O

OH

OH

CH2OH

OHC

C

CC

C

O

NH

OH

CH2OH

O

C

CH3

O


GANGLIOSIDES contain a heteropolysaccharide attached to C-1 of ceramide. The polysaccharide always contains at least one N-acetylneuraminic acid (sialic acid) residue at the non reducing end of the polysaccharide. The reducing end of the polysaccharide is linked to sphingosine by a glycosidic bond. The ABO blood group heteropolysaccharides are part of gangliosides imbedded in the red blood cell membrane.

The complex lipids, the phosphoglycerides, plasmalogens, sphingomyelins, cerebrosides, globosides, and gangliosides, are all components of cellular membranes. The sphingomyelins, cerebrosides, and gangliosides, are especially rich in the plasma membranes of nervous tissue.

The Phospholipases

The phospholipases are enzymes specific for the hydrolysis of phosphoglycerides. Phospholipase A1

Ganglioside

H2C

HC

CH

CH

HC

CH2H2C

CH2H2C

CH2H2C

CH2H2C

CH2H2C

CH2H2C

CH3

HN

HO

C

C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

H

H

CH2C

CH2C

C

C CH2CH3

H

HH

H

ONHC

O OC

CH3

O

HC

CH

HOH2C OH

OH

OOH

NH

H2C

O

C

CH3

O

O

OH

OH

OH

CH3

OOH

OH

CH2OH

O

O

OH

OH

CH2OH

O

OOH

O

OH

CH2OH O

OHO


hydrolyzes the ester bond between carbon one of glycerol and the fatty acid. The fatty acid on C1 of glycerol is usually a saturated fatty acid. Phospholipase A2 hydrolyzes the ester bond between carbon two of glycerol and the fatty acid. This fatty acid is usually an unsaturated fatty acid. Phospholipase B is the least specific of the phospholipases, it will hydrolyze the bonds between the fatty acid on carbon one of glycerol and/or between the fatty acid on carbon two of glycerol. Phospholipase C is specific for the hydrolysis of the ester bond between carbon three of glycerol and the phosphate and Phospholipase D hydrolyzes the ester bond between phosphate and the polar alcohol.

_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_

O

H2C

CH

H2C

O

O

CH3

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

C

O

CH3H2C

CH2H2C

CH2H2C

CC

H2C

CH2

H2C

CH2

H2C

CH2

H2C

C

O

H

H

PO

O

OCH2

H2CN

CH3H3C

CH3

Phospholipase A1

Phospholipase A2

Phospholipase C

Phospholipase D

Phospholipase B


THE FAT SOLUBLE VITAMINS The Fat Soluble Vitamins and Cholesterol are isoprenoid compounds. Isoprene (terpene) is the common precursor of these molecules.

VITAMIN A is a 20 carbon terpene obtained directly from animal sources or by the oxidative cleavage of the 40 carbon molecule, β-carotene obtained from yellow-orange vegetables. The body is capable of converting β-carotene into Vitamin A and able to interconvert one form of Vitamin A into another.

There are three active forms of this vitamin, RETINOL, RETINAL, & RETINOIC ACID. Each form of the vitamin has a different function within the body.

Retinol regulates gene expression during cell differentiation. Retinal, the aldehyde, is part of the light sensitive compounds required for vision. Retinoic acid is required for the integrity of the skin and it plays a minor role in gene expression.

Nonsaponifiable Lipids

Fat SolubleVitamins

Vitamin AVitamin DVitamin EVitamin K

Eicosanoids

ProstaglandinsLeukotrienes

Thromboxanes

Bile AcidsBile Salts

Bile Esters

SteroidHormones

ProgestinsGlucocorticoids

MineralocorticoidsAndrogensEstrogens

Cholesterol

�-Carotene


H2CC

CH

CH2

CH3

Isoprene

VITAMIN D is a group of related nonsaponifiable lipids. VITAMIN D3, also called Cholecalciferol, is formed nonenzymatically in the skin from the steroid 7-dehydrocholesterol, an intermediate of cholesterol biosynthesis. The active form of vitamin D, 1,25-Dihydroxycholecalciferol, is formed from vitamin D3 by two hydroxylation reactions. 25-Dihydroxycholecalciferol is formed in the liver, transported to the kidney where it is hydroxylated to 1,25-Dihydroxycholecalciferol. The active vitamin maintains normal calcium ion concentrations in the blood by stimulating the uptake of Ca+2 from the intestine, the re-up by the kidney, and by stimulating the reabsorption of Ca+2 from bone.

VITAMIN E, or α-TOCOPHEROL is believed to function as a scavenger of oxygen radicals and other free radicals in tissues performing oxidative metabolism. Its antioxidant action prevents damage to the unsaturated fatty acids in biological membranes.

VITAMIN K is a lipid vitamin obtained from plants. It is a required coenzyme for the synthesis of several of the proteins involved in hemostasis, blood coagulation. Vitamin K is a coenzyme for Vitamin K Dependent Glutamyl Carboxylase. This enzyme catalyzes the addition of a carboxyl group to specific glutamate residues within selected proteins of the coagulation cascade. The product of this reaction is a γ-carboxyglutamate side chain. The 2 negative charges present on this modified amino acid are involved in Ca2+ ion binding and localization of the the hemostatic proteins to the site of damage.

H2C

OHHC

O

COH

O

Retinol Retinal

Retinoic Acid

CH2

HO

OH

HOVitamin D3

(Cholecalciferol)

1,25-Dihydroxycholecalciferol

O

HO Vitamin E (�-Tocopherol)


THE EICOSANOIDS

The Eicosanoids are a group of compounds synthesized from the 20 carbon (eicosa) polyunsaturated fatty acid arachidonate. These compounds include the PROSTAGLANDINS, the THROMBOXANES, and the LEUKOTRIENES. The eicosanoids are “local” hormones (autocoids and/or paracoids). They are synthesized and secreted by specific cell types and produce a response in the cell that synthesized them (autocoid) or in neighboring cells (paracoid). They are “local” hormones because they are produced, released, and cause their effects in a confined region of the body. They are not released into the blood stream to produce an

O

O

Vitamin K

HC

NH

C

H2C CH

C

C

O

O

O

O

OHC

NH

CO

H2C

H2C C

O

O

CO2O2 H

Vit K

Vitamin K DependentGlutamyl Carboxylase

OH

SCH2

HC

HN

CHN

H2C C

O

OH

O

CH2C

H2C

HC C

NH2O

O

OH

OH

OLeukotriene C

O

O

COOH

OHProstaglandin H2

OHO

COOH

OHThromboxane B2


organism wide effect. If they get into the blood stream, the liver destroys them in one pass. Eicosanoids mediate a variety of physiological responses and different eicosanoids can produce opposite effects in the same tissue. For example they can:

1. cause smooth muscle contractions. 2. cause smooth muscle relaxation. 3. inhibit the secretion of HCL by the stomach. (COX-1) 4. inhibit the use of fatty acids for energy. 5. inhibit blood clotting. (prostaglandins released from endothelial cells - COX-2) 6. stimulate blood clotting. (thromboxanes released from platelets - COX-1) 7. regulate reproductive processes 8. regulate the synthesis of steroids 9. regulate nervous transmission. 10. mediate the sensation of pain. (COX-2) 11. mediate the inflammatory response. (COX-2)

Many of the eicosanoids are involved in inflammation, some stimulating the inflammatory response others suppressing it. Aspirin is anti-inflammatory because it irreversibly inhibits the key enzymes involved in prostaglandin and thromboxane synthesis - Cyclooxygenase (COX-1 & COX-2). Aspirin was the first Non Steroidal Anti-Inflammatory Drug (NSAIDS) discovered. Some of the modern NSAIDS designed to treat the pain of arthritis (Vioxx, Celebrex, Naproxen) target COX-2. However, these drugs can have dangerous side effects.

CHOLESTEROL Cholesterol and the other steroids are all isoprenoid compounds. The characteristic four ring steroid nucleus is sequentially built up from isoprene precursors. Cholesterol contains a total of 27 carbon atoms and is very slightly polar due to the hydroxyl group on C-3. Cholesterol is an important component of cellular membranes. It is oxidized to the bile acids, bile salts, and bile esters needed for the emulsification and digestion of dietary lipids. The hydroxyl group on C3 is esterified with a fatty acid to form Cholesterol Esters. The cholesterol esters are formed in LIPOPROTEINS - the supramolecular complexes that function to transport lipids in the blood. Cholesterol esters are the storage form of cholesterol.

Cholesterol is the precursor for the steroid hormones. Pregnenolone is a 21 carbon derivative of cholesterol and the precursor to all of the other steroid hormones. The PROGESTINS (progesterone) are synthesized from pregnenolone by a single enzymatic step. This enzyme catalyzes the rearrangement of the Δ5 double bond to Δ4 and the oxidation of the hydroxyl group on C3 to a ketone group. The progestins are synthesized by the ovaries and participate in control of the menstrual cycle and maintenance pregnancy. Progesterone is the precursor for the synthesis of the ADRENAL CORTICOSTEROIDs and the ANDROGENS. Adrenal corticosteroids, synthesized by the adrenal cortex, include the GLUCOCORTICOIDS and the MINERALOCORTICOIDS. Glucocorticoids participate in the control of carbohydrate, lipid and amino acid metabolism. Mineralocorticoids regulate monovalent ion concentrations (Na+, K+, HCO3–, and Cl–) in the tissues and they are also anti-inflammatory agents. The androgens (testosterone) are produced primarily by the testes and to a lesser extent the ovaries. They mediate the development of the primary and secondary sexual characteristics in the male and they have non-reproductive effects. The non-reproductive effects include promoting an increase in muscle mass in the upper body, an increase in bone growth, an increase in blood volume, an increase in upper body fat deposition and a decrease in lower body fat deposition.


ESTROGENS are synthesized from the androgens. They are produced primarily by the ovaries and to a lesser extent the testes. They mediate the development of the primary and secondary sexual characteristics in the female.

The French Paradox (FYI)

A diet high in saturated fats (saturated triacylglycerols) has been implicated as a causative agent for coronary artery disease and stroke. It has been suggested that Americans limit the amount of fats, especially saturated fats, in their diets. The French diet is as rich or richer in saturated fats when compared to the American diet and yet the French have a lower incidence of cardiovascular disease – The French Paradox. Biochemists, nutritionists, and physicians looked closely at the diet of the French and noted that one of the major differences between this and the American diet is the amount of red wine consumed by the French. When red wine was examined it was found to contain relatively high concentrations of a group of

HO

Cholesterol {C27}

HO OH

OH

C O

OH

Bile Acid(Cholic Acid)

CH3C O

CH3

CH3

O

Progestins {C21}(Progesterone)

OH

CH3

CH3

O

Androgens {C19}(Testerone)

OHCH3

HO

Estrogens {C18}( -Estradiol)

CO CH2OH

CH3

CH3

O

OHHOGlucocorticoids {C21}

(Cortisol)

CO CH2OH

CH3

CH

O

OHO

Mineralocorticoids {C21}(Aldosterone)


Phytochemical compounds called Polyphenols. One of the more abundant polyphenols found in red wine was the molecule Resveratrol. Resveratrol can be found in high concentrations in the skins of red wine grapes, peanuts, mulberries, chocolate, several other fruits and nuts. The plant produces this compound as a fungicide, it destroys fungi that invade the fruit and cause it to rot. In animals Resveratrol, and the other polyphenols, have been shown to be antioxidants, anticoagulants, anti-inflammatory agents, to have anticancer effects and to increase high-density lipoprotein (HDL), the “good cholesterol”. The mechanism by which Resveratrol functions is open to debate. Several groups have postulated that this compound mimics the effects of the estrogens, binding to the estrogen receptor and stimulating the expression of the estrogen controlled genes. Others have postulated that Resveratrol specifically inhibits COX-1, inhibiting platelet aggregation and blood clotting. It has been difficult to isolate and purify these compounds because they are easily oxidized and destroyed by the oxygen in the air. Resveratrol has become available on the internet and in “health food stores” as a dietary supplement. However, its potency, bioavailability, and effectiveness is open to question.


OH

OH

HO

��

Documents

Lipids - Marquette University1. Describe the structural differences between fats and oils. 2. Describe the structural differences between saturated, monounsaturated, polyunsaturated,