Download The Lipids

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
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©Kevin R. Siebenlist, 2015
IV.
V.
functions of the molecule.
Describe the function and specificity of the Phospholipases.
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.
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©Kevin R. Siebenlist, 2015
O
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Caprate (Capric Acid) - 10 carbons, 0 double bonds - 10:0
O
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Laurate (Lauric Acid) - 12 carbons, 0 double bonds - 12:0
O
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Myristate (Myristic Acid) - 14 carbons, 0 double bonds - 14:0
O
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Palmitate (Palmitic Acid) - 16 carbons, 0 double bonds - 16:0
O
H2
C
H2
C
H 3C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Stearate (Stearic Acid) - 18 carbons, 0 double bonds - 18:0
O
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Arachidate (Arachidic Acid) - 20 carbons, 0 double bonds - 20:0
O
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Lignocerate (Lignoceric Acid) - 24 carbons, 0 double bonds - 24:0
O
H2
C
H2
C
H3C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
Cerotate (Cerotic Acid) - 26 carbons, 0 double bonds - 26:0
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©Kevin R. Siebenlist, 2015
O
H
H
C
C
C
H2
H2
C
C
H2
H2
C
C
C
H2
C
H2
O
CH 2
H 2C
Palmitoleate
(Palmitoleic Acid)
16 carbons, 1 double bond
between C9 & C10 - 16:19
CH 2
H 2C
CH 2
H 3C
O
H2
C
H
H
C
C
CH 2
CH 2
H 2C
H
C
C
C
H2
CH2
H2C
O
Oleate
(Oleic Acid)
18 carbons, 1 double bond
between C9 & C10 - 18:19
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
Linoleate (Linoleic Acid)
18 carbons, 2 double bonds
between C9 & C10 and C12 & C13 - 18:29,12
CH2
H2C
CH3
H
H
H
C
C
H2
CH2
CH2
C
H2
H2
C
C
H2
C
C
H2
O
H2
C
C
H
H2
C
-Linolenate (Linolenic Acid)
18 carbons, 3 double bonds between
C9 & C10, C12 & C13, and C15 & C16 - 18:39,12,15
C
H
O
H2
C
C
C
C
C
H2
CH2
C
H
C
H2
O
H2
C
C
H
C
H2
H2
C
CH 2
H 3C
H
C
H2
H2
C
CH 2
H 2C
H 2C
O
H2
C
C
CH3
H
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©Kevin R. Siebenlist, 2015
H
H
H
C
O
C
C
H2
C
H2
C
H2
C
H2
C
C
O
CH2
C
H
CH2
H
H2
C
H2
C
C
C
C
H2
C
H2
CH3
H
γ-Linolenate (Linolenic Acid)
18 carbons, 3 double bonds between
C6 & C7, C9 & C10, and C12 & C13 - 18:3Δ6,9,12
H
H
C
C
H
C
O
H2
C
C
H2
C
CH2
H2
C
C
H
CH2
H2C
H2
C
C
H
O
C
H2
H2
C
C
H2
CH3
C
C
C
H
H
H
Arachidonate (Arachidonic Acid)
20 carbons, 4 double bonds between
C5 & C6, C8 & C9, C11 & C12,
and C14 & C15 - 20:4Δ5,8,11,14
Fatty acids can be SATURATED (no carbon-carbon double bonds), MONOUNSATURATED (one carboncarbon 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.
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©Kevin R. Siebenlist, 2015
“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.
H
H2
C
H2
C
H3C
C
H2
H2
C
C
H2
O
H2
C
C
C
C
H2
H2
C
C
H2
H2
C
C
C
H2
C
H2
O
H
H
H2
C
H3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
O
H2
C
C
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
O
H
H
H2
C
H2
C
H3C
C
H2
H
H2
C
C
C
H2
O
H2
C
C
C
C
H
H
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
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 bond are conjugated.
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 “pretty” crystalline matrix.
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©Kevin R. Siebenlist, 2015
H3C
CH2
H2C
CH2
H2C
CH2
H
C
H
C
H2
C
C
H
C
H2
C
C
H2
H2
C
C
H2
H2
C
O
C
H2
C
H
O
O
H
H
C
C
H
H2
C
H
C
H
C
C
H2
H3C
O
C
C
H2
C
C
C
H2
C
H2
C
H2
C
H2
H2
C
H2
C
H2
C
H
H
H
H
H2
C
H3C
C
C
C
C
C
C
H
H
H
H
O
H2
C
C
H2
C
H2
C
C
H2
C
H2
C
C
C
H2
C
H2
O
H
O
C
H2C
H3C
CH2
CH2
H2C
H
C
C
CH2
C
H
C
H
C
H2C
C
C
H
H
7
O
H2C
H
H
H2C
C
H
C
H
C
H
©Kevin R. Siebenlist, 2015
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,Ntrimethylethanolamine. Inositol is a six carbon cyclic polyalcohol. Glycerol is the second most
abundant precursor of the saponifiable lipids.
OH
O
H2
C
H 2C
CH
OH
HO
C
HO
CH
H 2C
CH 2
H2
C
O
C
H2
H2
C
NH 3
HO
NH 3
Ethanolamine
OH
Choline
Serine
Glycerol
OH
OH
OH
C
C
H
C
H
H
H
OH
C
H
C
C
OH
OH
H
N
CH 3
C
H 2 CH
3
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.
OH
H2
C
HO
CH
NH 3
H2
C
H
C
CH
C
H
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
Sphingosine
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.
8
©Kevin R. Siebenlist, 2015
H2
C
H2
C
HO
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
H2
C
H2
C
HO
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
H
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
C
HO
C
H
C
H2
C
H2
C
H2
C
H2
C
H2
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
CH 3
H2
C
H
C
HO
C
H
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
YZ YZ YZ YZ YZ YZ YZ YZ YZ YZ YZ
Saponifiable Lipids
Waxes
Triacylglycerols
Gangliosides
Glycerol Lipids
Phosphoglycerides
Sphingolipids
Ether Lipids
(Plasmalogens)
Sphingomyelins
Glycosphingolipids
Globosides
Cerebrosides
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©Kevin R. Siebenlist, 2015
The WAXES
O
O
Spermaceti CH3(CH2)14COO(CH2)15CH3
O
O
Beeswax CH3(CH2)24COO(CH2)29CH3
O
O
Carnuba Wax CH3(CH2)30COO(CH2)33CH3
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.
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).
H2
C
O
C
H2C
O
HC
O
H2
C
C
O
H2C
O
C
H2
C
H2
C
C
H2
C
H2
C
H2
H2
C
H2
C
H2
C
C
H2
C
H2
C
H2
H2
C
H2
C
H2
C
C
H2
C
H2
C
H2
H2
C
H2
C
H2
C
C
H2
C
H2
C
H2
H2
C
H2
C
H2
C
C
H2
C
H2
C
H2
H2
C
H2
C
H2
C
C
H2
C
H2
H2
C
H2
C
C
H2
C
H2
C
H2
C
H2
CH3
H2
C
H2
C
H2
C
C
H2
C
H2
H2
C
C
H2
H2
C
C
H2
C
H2
CH3
CH3
O
10
©Kevin R. Siebenlist, 2015
CH 3
H 2C
H2
C
O
C
H 2C
O
CH
H2
C
C
H2
O
O
H 2C
C
C
H2
H2
C
CH 2
H 2C
C
C
H
H2
H2
H2
H2
H
C
C
C
C
C
C
C
CH 3
H2
H2
H2
C
H2
C
H2
H2
C
H2
C
H2
C
C
H2
CH 2
H 2C
H2
C
C
H2
C
H2
O
C
H2
H2
C
C
O
H2
C
CH 2
H 2C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
H
H3C
C
C
H2
H
C
H2C
H
C
C
H2
C
O
C
H2C
O
CH
O
H2C
O
C
O
C
H2
H2
C
C
O
C
H2
H2
C
H2
C
H2
C
C
H2
H2
C
C
H2
C
H2
H2
C
H2
C
C
H2
H2
C
C
H2
C
H2
H2
C
H2C
C
H2
H
C
H
C
H2 H H2
H2
H2
H2
CH3
C
C
C
C
C
C
C
C
C
C
H2
H2
H2
H2
H H2
H
C
C
H2
C
H2C
CH2
H2C
CH2
H2C
CH2
H2C
11
CH3
©Kevin R. Siebenlist, 2015
When a monounsaturated and / or a polyunsaturated triacylglycerol is partially hydrogenated, saturated and /
or “TRANS FATS” result.
H
O
H2
C
C
O
H2
C
C
H2
H 2C
C
H2
C
H 2C
O
C
H2
H2
C
O
CH
C
H2
C
C
H2
C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H
H2
C
H2
C
C
H2
C
H2
H2
C
C
C
H2
H2
C
C
H2
O
H2
C
H2
C
H2
C
C
H2
C
H2
H2
C
C
H2
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
CH 3
CH 3
O
H
O
H2
C
C
O
H2
C
C
H2
H 2C
C
H 2C
O
C
H2
H2
C
C
H2
H2
C
C
C
C
H2
C
H2
C
H2
C
C
H2
H
H2
C
H2
C
H2 O
H2
H2
H2
C
C
C
C
C
C
C
C
H2
H2
H2
H
O
C
H2
H2
C
O
CH
C
H2
H2
C
C
H2
H2
C
C
H H2
C
C
C
H2
H2
C
C
H2
C
C
H2
H2
C
C
H H2
C
H2
H2
C
CH 3
CH 3
H2
C
C
H2
C
H2
CH 3
H
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
O
O
P
H 2C
O
CH 2
Phosphatidate
O
H 2C
H 2C
H 2C
CH
O
H 2C
C
O
H2
C
O
C
O
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
CH 3
H2
C
C
H2
C
H2
12
CH 2
C
C
H
H2 H
H2
H2
H2
H2
C
C
C
C
C
C
C
C
C
CH 3
H2
H2
H2
H2
©Kevin R. Siebenlist, 2015
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.
CH3
H2C
Phosphatidylcholine
(Lecithin)
O
H2
C
O
H2C
H3C
N
P
O
CH2
O
HC
CH3
O
H2C
CH3
C
C
O
H2
C
H2
C
C
H2
C
H2
O
H2
C
O
H2
C
H2
C
C
H2
C
H2
H2
C
C
H2
CH2
H2C
H2C
H2
C
C
H2
C
H2
CH2
C
H
C
H2 H H2
H2
H2
H2
C
C
C
C
C
C
C
C
C
CH3
H2
H2
H2
H2
PHOSPHATIDYLETHANOLAMINE is formed when ethanolamine is esterified to the phosphate.
H
O
H2
C
H 2C
O
P
O
C
CH 2
O
CH
NH 3
C
O
H2
C
H2
C
O
O
H 2C
H
C
O
C
H2
H2
C
C
H2
C
H2
H
C
H
H 2C
C
H 2C
C
C
H 2C
C
H 2C
C
H
C
H
H2
C
C
H2
C
H2
CH 3
H2
H2
H2
H2
H2
H2
H2
H
H
C
C
C
C
C
C
C
C
C
C
C
C
C
CH 3
H2
H2
H2
H2
H2
H2
Phosphatidylethanolamine
PHOSPHATIDYLSERINE is made by attaching the side chain hydroxyl group of the amino acid serine to
phosphatidate.
13
©Kevin R. Siebenlist, 2015
H
O
H2
C
O
H
C
C
O
P
O
O
O
C
CH 2
CH
NH 3
H2
C
O
C
C
H2
O
H 2C
H2
C
O
C
O
H2
C
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
C
H2
C
H2
C
C
H 2C
C
H2
C
H
H 2C
H2
C
H
C
H2
CH 3
C
H2
H2 H
H2
H2
H2
C
C
C
C
C
C
C
CH 3
H2
H2
H2
C
H2
Phosphatidylserine
PHOSPHATIDYLINOSITOL is formed by adding inositol.
OH
OH
H
C
C
OH
C
H
OH
H
H
C
C
H
C
O
O
H
P
H 2C
CH
H 2C
H2
C
O
O
C
O
H2
C
C
O
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 2
H 2C
OH
O
C
H2
H2
C
C
H2
H2
C
C
H2
C
H2
CH 2
C
C
H2
C
CH 2
H 2C
Phosphatidylinositol
CH 2
O
CH 3
H 2C
H
H
H2
C
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
PHOSPHATIDYLGLYCEROL is formed when a second molecule of glycerol is attached.
HO
C
H2
C
H
H
O
OH
O
C
H2
P
O
O
HC
O
H2C
O
H2
C
O
C
C
O
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
H
C
Phosphatidylglycerol
CH2
H2
C
C
H2
C
H2
C
H2C
C
C
H2C
H
H2
C
C
H2
C
H2
CH3
H2 H H2
H2
H2
C
C
C
C
C
C
C
CH3
H2
H2
H2
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.
14
©Kevin R. Siebenlist, 2015
OH
H2
C
H2
C
O
CH
C
H 2C
O
O
O
P
O
C
H2
C
H2
O
O
P
O
H2
C
CH
O
O
H 2C
H
CH 2
H 2C
CH 2
H 2C
H 2C
CH 2
H 2C
H 2C
CH 2
H 2C
H 2C
CH 2
H 2C
CH 3
H 3C
CH 2
CH 2
H 2C
H 2C
C
C
H
CH 2
CH 2
C
CH 2
H 2C
H 2C
Diphosphatidylglycerol
(Cardiolipin)
CH 2
CH 2
CH 2
CH 2
CH 2
CH 2
CH 2
O
H 2C
H 2C
H 2C
H 2C
C
CH 2
CH 2
CH 2
O
H 2C
H 2C
H 2C
O
C
CH 2
CH 2
H 2C
O
H2
C
O
CH
C
CH 2
H 2C
O
H
CH 2
H 2C
C
CH 2
H
H 2C
CH 2
H 2C
H 2C
CH 2
CH 2
H 2C
H 3C
CH 3
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.
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.
15
©Kevin R. Siebenlist, 2015
H 3C
CH 3
N
H 2C
O
O
P
O
CH 3
CH 2
H 2C
O
Ether Lipid
H 2C
H2
C
O
H2
C
C
H 2C
H2
C
O
C
H2
H2
C
C
H2
O
H 2C
P
O
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
H2
C
C
H2
H
H2
C
H
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
CH 3
N
O
H2
C
C
H2
H 3C
O
CH 2
H 2C
CH
CH 3
H 2C
CH 2
CH 3
CH 2
O
Platelet Activating Factor
H 2C
CH
O
C
H 2C
H2
C
H2
C
C
H2
O
O
CH 3
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
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.
H 3C
N
H 2C
O
O
P
O
CH 3
CH 3
CH 2
O
H 2C
Plasmalogen
H 2C
H 2C
CH
H2
C
O
C
H 2C
H
C
O
CH 3
H 2C
CH 2
O
C
H
H2
C
H2
C
C
H2
C
H2
H2
C
H2
C
C
H2
C
H2
H2
C
H2
C
C
H2
C
C
H2
C
C
H2
16
CH 2
H
C
H2
H
H2
C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
CH 3
©Kevin R. Siebenlist, 2015
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.
OH
H2
C
H 3C
H2
C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
H2
H
Ceramide
H
H 3C
C
H2
H2
C
CH
C
H2
C
H
C
C
H
C
H2
H2
C
C
H2
H2
C
C
C
H2
C
H2
O
CH 2
C
OH
CH
NH
H2
C
C
H
CH 2
CH 2
H
C
H
C
C
H2
C
H
SPHINGOMYELINS contain a phosphate group in ester linkage to C-1 of the sphingosine moiety of
ceramide. A choline molecule is usually esterified to the phosphate. On occasion ethanolamine can be
found linked to the phosphate.
OH
H2
C
H 3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H
H
H 3C
C
H2
H
C
C
H2
CH
C
H
C
C
H
CH 2
C
CH 2
C
CH 2
C
O
C
H2
H2
C
C
H2
H2
C
C
H2
O
H 2C
C
C
H2
P
O
NH
H2
C
O
H2
C
CH
H
C
H
H2
C
O
CH 2
N
H 3C
CH 3
CH 3
Sphingomyelin
H
The Phosphoglycerides, Plasmalogens, and Sphingomyelins are, as a group, called the PHOSPHOLIPIDS since
17
©Kevin R. Siebenlist, 2015
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.
H 2 COH
O
OH
H2
C
H 3C
H2
C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
C
H2
H2
C
C
H2
H
C
C
H2
CH
CH
C
H
H2
C
H 3C
H2
C
CH 2
C
C
H
O
OH
C
H2
H2
C
C
H2
H2
C
C
H2
Cerebroside
C
C
H2
O
CH 2
C
H2
C
C
H
C
H2
OH
NH
H
OH
H2
C
H
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 Nacetylgalactosamine
OH
H2
C
H3C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
H
C
C
H2
C
H
C
H
H3C
H2
C
C
H2
H
CH2
C
C
C
H
C
H2
C
C
H2
H2
C
C
H2
H2
C
C
H2
O
O
C
C
C
C
H2
CH2OH
H2
C
HN
H
H2
C
H
C
C
OH
C
C
O
CH2OH
O
CH2OH
C
OH
CH2
C
OH
C
H
Globoside
O
O
O
C
C
C
C
OH
OH
OH
C
C
NH
O
C
C
CH3
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.
18
©Kevin R. Siebenlist, 2015
CH 3
O
O
C
O
C
NH
O
H
C
CH 2 OH
OH
O
CH 2 OH
CH
HO
O
HOH 2 C
OH
O
OH
OH
H2C
H 2C
O
O
OH
CH 2 OH
OH
O
HC
H
N
HO
CH 2
CH
NH
H 2C
OH
C
O
CH
O
CH 3
H 2C
CH 2
OH
CH 2
H 2C
OH
OH
CH 2
HC
O
CH 3
C
O
O
OH
O
O
OH
Ganglioside
H 2C
CH 2
H 2C
CH 2
H
C
CH 2
C
H 2C
CH 2
H
CH 2
C
H 2C
H 2C
CH 2
H
C
CH 2
H
C
H
C
H 2C
H
CH 2
CH 3
H 2C
CH 3
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
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.
19
©Kevin R. Siebenlist, 2015
Phospholipase D
H 3C
CH 3
N
H 2C
O
O
P
CH 3
CH 2
O
CH
H2
C
O
O
H 2C
C
O
H 2C
Phospholipase A2
H 2C
Phospholipase B
CH 2
Phospholipase C
O
C
H2
C
O
C
H2
H2
C
C
H2
CH 3
H 2C
H 2C
H2
C
H2
C
C
H2
C
H2
H2
C
C
H2
H2
C
C
H2
C
C
C
H2
CH 2
H
H2 H
H2
H2
H2
H2
C
C
C
C
C
C
C
C
C
CH 3
H2
H2
H2
H2
Phospholipase A1
_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_)_
Nonsaponifiable Lipids
Cholesterol
Fat Soluble
Vitamins
Eicosanoids
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Prostaglandins
Leukotrienes
Thromboxanes
Bile Acids
Bile Salts
Bile Esters
Steroid
Hormones
Progestins
Glucocorticoids
Mineralocorticoids
Androgens
Estrogens
THE FAT SOLUBLE VITAMINS
The Fat Soluble Vitamins and Cholesterol are isoprenoid compounds.
Isoprene (terpene) is the common precursor of these molecules.
20
CH 3
CH 2
C
H 2C
C
H
Isoprene
©Kevin R. Siebenlist, 2015
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.
-Carotene
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.
H2
C
H
C
OH
O
Retinol
Retinal
O
C
OH
Retinoic Acid
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.
OH
HO
CH 2
Vitamin D3
(Cholecalciferol)
HO
1,25-Dihydroxycholecalciferol
VITAMIN E, or α-TOCOPHEROL is believed to function as a scavenger of oxygen radicals and other free
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radicals in tissues performing oxidative metabolism. Its antioxidant action prevents damage to the
unsaturated fatty acids in biological membranes.
O
Vitamin E (-Tocopherol)
HO
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 γcarboxyglutamate 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.
O
Vitamin K
O
O
NH
HC
O
C
H2
C
H2
C
O
Vitamin K Dependent
Glutamyl Carboxylase
NH
HC
C
O
Vit K
O
C
H2
C
C
O
C
O
CH
O
CO2
O2
H
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
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.
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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)
O
COOH
COOH
HO
O
O
OH
OH
Prostaglandin H2
Thromboxane B2
OH
O
OH
S
CH 2
O
Leukotriene C
HC
O
C
H
N
C
H2
C
H2
C
C
OH
O
HN
O
H2
C
H
C
C
OH
NH 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.
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Cholesterol {C27}
HO
H 3C
OH
Bile Acid
(Cholic Acid)
C
Progestins {C21}
(Progesterone)
O
OH
Androgens {C19}
(Testerone) CH
O
CH 3
OH
O
Glucocorticoids {C21}
(Cortisol) HO
CH 2 OH
CH 3
C
OH
CH 3
3
O
O
CH 3
Estrogens {C18}
(-Estradiol)
C
CH 3
OH
HO
O
CH 3
OH
O
Mineralocorticoids {C21}
(Aldosterone) HO
O
CH
CH 2 OH
C
CH 3
HO
O
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
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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
Phytochemical compounds called Polyphenols.
OH
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 HO
fungi that invade the fruit and cause it to rot. In
OH
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.
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