Lipid Chemistry

Dr T.B.Nyambo
Department of Biochemistry
School of Medicine
MUCHS
29 September 2005
 Lipid chemistry
The word lipid originated from a Greek
word lipos meaning fat.
Lipids are a class of heterogeneous
group of substances of biological origin
that are soluble in organic solvents such
as chloroform but are only sparingly
soluble, if any at all in water.
 They are amphipathic: form bilayers
and micelles in aqueous solution.
.
 Function of Lipids
The have six main functions in the body mainly:
They serve as structural components of
biological membranes.
They provide energy reserves, predominantly
in the form of triacylglycerols.
Both lipids and lipid derivatives serve as
vitamins and hormones.
 Function of Lipids
Lipophilic bile acids aid in lipid solubilization
Insulation
Cushioning.(shock absorbers)
Signal transduction.
Sleep induction lipids such as a fatty acid primary
amide called oleamide.(cis-9-Octadecenamide )
Endogenous cannabinoids. Such as Anandamide(N-
arachidonoylethanolamine)
 Classification of Lipids
1.Simple Lipids
Triglycerides, neutral fats: Found in adipose
tissue, butterfat, lard, fish oils, olive oil, corn
oil, etc. Esters of three molecules of fatty
acids plus one molecule of glycerol; the fatty
acids may be different.
Waxes: beeswax, head oil of sperm
whale.Composed of esters of fatty acids with
alcohol other than glycerol; of industrial and
medicinal importance.
 Classification of Lipids
2.Compound Lipids
Phospholipids (phosphatides): Found chiefly in animal
tissues. Substituted fats, consisting of phosphatidic acid;
composed of glycerol, fatty acids, and phosphoric acid bound in
ester linkage to a nitrogenous base.
Lecithin: Found in brain, egg yolk, and organ meats.
Phosphatidyl choline.Phosphatide linked to choline; a lipotropic
agent; important in fat metabolism and transport; used as
emulsigying agent in the food industry.
Cephalin: Occurs predominantly in nervous tissue.
Phosphatidyl ethanolamine; phosphatide linage to serine or
ethanolamine; plays a role in blood clotting.

Plasmalogen: Found in brain, heart, and muscle. Phosphatidal

ethanolamine or choline; phosphatide containing an aliphatic
aldehyde.
 Classification of lipids
2.Compound Lipids
Sphingomyelin: Found in nervous tissue, brain, and
red blood cells. Sphingosine-containing phosphatide.
Glycolipids:
Cerebroside: myline sheaths of nerves, brain, and other
tissues. Yields on hydrolysis of fatty acids, sphingosine,
galactose (or glucose).
Ganglioside: brain, nerve tissue, and other selected tissues,
notably spleen; contains a ceramide linked to hexose
(glucose or galactose), neuraminic acid, sphingosine, and
fatty acids.
Sulfolipid: white matter of brain, liver, and testicle; also
plant chloroplast. Sulfur-containing glycolipid; sulfate present
in ester linkage to galactose.
Proteolipids: brain and nerve tissue. Complexes of protein
and lipids having solubility properties of lipids
 Classification of Lipids
3.Terpenoids and Steroids
Terpenes: Found in essential oils, resin acids, rubber, plant
pigments. Large group of compounds made up of repeating
isoprene units; Vitamin A of nutritional interest; fat soluble
Vitamin E and K, which are also related chemically to
terpenes.
Sterols:
Cholesterol: found in egg yolk, dairy products, and animal
tissues. A consituent of bile acids and a precursor of
Vitamin D.
Bile acids
Ergosterol: found in plant tissues, yeast, and fungi.
Converted to Vitamin D2 on irradiation.
7-dehydrocholesterol: found in animal tissues and
underneath skin. Converted to D3 on irradiation.
Androgens and estrogens: (Sex hormones) Found in
ovaries and testes.
Adrenal corticolsteroids: adrenal cortex, blood.
 Terpenoids
.
 Classification of Lipids
4. Derived lipids
Fatty acids: occur in plant and animal foods.
Obtained from hydrolysis of fats; usually
contains an even number of carbon atoms
and are straight chain derivatives.May be
saturated or unsaturated
Eicosanoids: Prostaglandins, Thromboxanes
and Leukotrienes - oxidized derivatives of C-
20 fatty acids
 Classification of common phospholipids, glycolipids, and
triacylglyerides

.
 Fatty acid Nomenclature

There are three ways of naming unsaturated fatty

acids.
The first one is the symbolic nomenclature. Which is
given as as a: b (x, y, z) where a is the number of carbon
atoms in the chain, b is the number of double bonds,
and x, y, and z are the positions of the start of the
double bonds counting from the carboxyl end (C1)
Saturated fatty acids contain only C-C bonds.
Whereas monounsaturated fatty acids contain one
C=C bond.
The polyunsaturated fatty acids contain more than one
C=C.double bonds which are usual in the cis position
 Cis and Trans types
.
 Saturation Vs Unsaturation
Multiple Sites of Unsaturation are
Polyunsaturated Fatty Acids
Single Sites of Unsaturated are
Monounsaturated Fatty Acids.
Linoleic and Linolenic are essential fatty
acids in the human diet (Arachidonic Acid
can be synthesized from Linolenic acid.
 Nomenclature of fatty acids
The second way to name fatty acids is by using the
systematic name, which refers to the IUPAC
nomenclature. ]
This nomenclature gives the number of carbon
atoms for example, hexadecanoic acid is indicated
as thus16:0. If the fatty acid is unsaturated, the base
name reflects the number of double bonds as shown
in octadecatrienoic acid for 18:3 9,12,15)which has
three double bonds at C9, 12 and 15
.Another method is to refer to the common name for
example, palmitoleic, stearic oleic acid etc.
 Fatty acids

Fatty acids consist of a hydrocarbon chain with

a carboxylic acid at one end.
A 16-carbon fatty acid: CH3(CH2)14-COO-
Non-polar- CH3(CH2)14-COO - polar
A16-carbon fatty acid, with one cis double bond
between carbon atoms 9 and 10 may be
represented as 16:1 cis9.
Double bonds in fatty acids usually have the
cis configuration. Most naturally occurring fatty
acids have an even number of carbon atoms.
 Fatty acid Nomenclature
Another alternative to the symbolic
representation of fatty acids, in which the
carbon atoms are numbered.
We use the Greek alphabet (, , , ) to
identify the location of the double bonds in
unsaturated fatty acids.
The "alpha" carbon is the carbon closest to the
carboxyl group (carbon number 2), and the
"omega" is the last carbon of the chain because
omega is the last letter of the Greek alphabet.
 Nomenclature
.
 Examples of fatty acids with their common names
14:0 myristic acid
16:0 palmitic acid
18:0 stearic acid
18:1 cis9 oleic acid
18:2 cis 9,12 linoleic acid
18:3 cis 9,12,15 linonenic acid
20:4 cis 5,8,11,14 arachidonic acid
20:5 cis 5,8,11,14,17 eicosapentaenoic acid (an
omega-3 fatty acid because of double bond 3 C
from distal end)
 Melting Point is Proportional to chain length

Symbol common name systematic name structure mp(C)

.
12:0 Lauric acid dodecanoic acid CH3(CH2)10COOH 44.2

14:0 Myristic acid tetradecanoic acid CH3(CH2)12COOH 52

16:0 Palmitic acid Hexadecanoic acid CH3(CH2)14COOH 63.1

18:0 Stearic acid Octadecanoic acid CH3(CH2)16COOH 69.6

20:0 Arachidic aicd Eicosanoic acid CH3(CH2)18COOH 75.4

 Unsaturation lowers the melting point
Melting
# of carbon
Fatty acid Structure point
atoms
(C)

.
Myristic CH3(CH2)12COOH
14 54
acid

Palmitic CH3(CH2)14COOH
16 63
acid

Stearic acid 18 CH3(CH2)16COOH 70

Oleic acid 18 CH3(CH2)7CH=CH(CH2)7COOH 4

Linoleic CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH
18 -5
acid

Linolenic CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7C
18 -11
acid OOH
 Fatty acids

.
 Hydrogenation of Vegetable Oils

Vegetable oils (liquids) are generally less

expensive to produce than animal fats (solids).
Some of the carbon-carbon double bonds and
can be reduced with hydrogen to make them
chemically identical to the triacylglycerols in
animal fats.
Such products melt above room temperature.
 Eicosanoids
Arachidonic acid is a precursor of a large number of
fatty acid derivatives often present in tiny
concentrations.
These derivatives have profound effects on cellular
physiological or pathophysiological reactions. Due to
their diversity, these compounds have been classified
according to the type of their enzymatic formation.
Thus, the term prostanoids relates strictly to the
products of the cyclooxygenase pathway and includes
prostaglandins, prostacyclins, and thromboxanes.
The lipoxygenase products include leukotrienes,
lipoxins, and various peroxy- or hydroxy-fatty acid
derivatives
 Structure of Arachadonic Acid in
Hairpin conformation
.
 Eicosanoids

.
 Prostaglandins and Leucotriens
.
 Glycerol is the Building Block of TAGs
. H2C OH

HC OH

H2C OH

GLYCEROL
(C3H8O3)
 Stereochemistry of Glycerol
Glycerol is an achiral molecule.
Can it be chiral?? Orient glycerol with the OH on C2 pointing to
the left. Then replace the OH of C1 with OD, where D is
deuterium. Now the two alcohol substituents on C1 and C3 are
not identical and the resulting molecule is chiral.
By rotating the molecule such that the H on C2 points to the back,
and assigning priorities to the other substituents on C2 as
follows: OH =1, DOCH2 =2, and CH2OH = 3, it can be seen
that the resulting molecule is in the S configuration. Hence we
say that C1 is the proS carbon. Likewise, if we replaced the OH
on C3 with OD, we will form the R enantiomer. Hence C3 is the
proR carbon. This shows that in reality we can differentiate
between the two identical CH2OH substituents. We say that
glycerol is not chiral, but prochiral.
 Stereochemistry of Glycerol
.
 Nomenclature of Triacylglycerol
Triacylglycerols consist of the trihydric alcohol glycerol
esterified, almost invariably, with long-chain fatty acids.
When the two primary hydroxyl groups are esterified with
different fatty acids, the resulting triacylglycerol can be
asymmetric and thus can display "optical activity", although
this is usually too low to be measured.
The conventional D/L or R/S systems could designate such
enantiomers without ambiguity with simple molecules
The conventional D/L or R/S systems is not applicable for
complex mixtures of triacylglycerols found in nature.
Such problems can be avoided if the stereochemistry of
triacylglycerols and other glycerolipids is described by the
"stereospecific numbering" (sn) system as recommended by
a IUPAC-IUB commission.
 Fischer projection of a natural L-glycerol

The secondary
hydroxyl group is
shown to the left of
C-2; the carbon
atom above this
then becomes C-1
while that below
becomes C-3, and
the prefix sn is
placed before the
stem name of the
compound. The
term triacyl-sn-
glycerol rather
than triglyceride.
 Triacylglycerol(TAG)
.
 Triacylglycerol
.
 DI- AND MONOACYLGLYCEROLS
.
 Common glycerophospholipids
.

37
 Glycerophospholipids
.

An ester linkage forms when a hydroxyl

reacts with a carboxylic acid, with loss of water.
 Phosphatidate

In phosphatidate, fatty acids are esterified to the hydroxyls on C1 and C2,

while the C3 hydroxyl is esterified to phosphate
 Glycerophospholipids

In most glycerophospholipids (phosphoglycerides), the phosphate is in turn esterified to

an alcohol of one of the following polar head groups: serine, choline, ethanolamine,
glycerol, or inositol (designated X at right) The two fatty acids tend to be non-
identical. They may differ in length and/or the presence or absence of double bonds.
Phosphatidylcholine, with choline as polar head group

.
Phosphatidylinositol, with inositol as polar head group

.
 Ether linkages(Plasmalogens)
.
 Platelet Activating Factor (PAF)
One of the most potent alkyl ether plasmalogens is
platelet activating factor (PAF: 1-O-1'-enyl-2-acetyl-
sn-glycero-3-phosphocholine) which is a choline
plasmalogen in which the C-2 (sn2) position of
glycerol is esterified with an acetyl group insted of a
long chain fatty acid.
PAF functions as a mediator of hypersensitivity,
acute inflammatory reactions and anaphylactic
shock. PAF is synthesized in response to the
formation of antigen-IgE complexes on the surfaces
of basophils, neutrophils, eosinophils, macrophages
and monocytes.
 PAF
.
 Glycerophospholipid

Each glycerophospholipid has: a polar region [glycerol, carbonyl oxygens of

fatty acids, phosphate,and the polar head group (designated X above)]
two non-polar hydrocarbon tails of fatty acids
 Sphingosine
.
 The amino group of sphingosine can form an amide
bond with a fatty acid carboxyl, to yield a ceramide.

.
 Sphingomyelin,

Sphingomyelin, a ceramide with a phosphocholine or

phosphoethanolamine head group, is a common
constituent of plasma membranes. Sphingomyelin, with
a phosphocholine head group, is comparable in size and
shape to the glycerophospholipid phosphatidyl choline
 Cerebroside

A cerebroside is a sphingolipid (ceramide) with a monosaccharide

such as glucose or galactose as polar head group .A ganglioside is a ceramide
with a polar head group that is a complex oligosaccharide, including the acidic
sugar derivative sialic
 Cerebroside(a) and Ganglioside(b)
.
 GM1

.
 Nomenclature of Gangliosides
For convenience they are abbreviated by a
short-hand nomenclature system proposed by
Svennerholm in which:
M, D and T refer to mono-, di- and
trisialogangliosides, respectively
numbers 1, 2, 3, etc refer to the order of
migration of the gangliosides on thin-layer
chromatography.
To indicate variations within the basic
structures, further subscripts are added, e.g.
GM1a, GD1b
 Sphingosine-1-phosphate (S1P)

In addition to being a precursor for sphingolipid synthesis,

sphingosine and its phosphorylated derivative sphingosine-1-phosphate
(S1P) have antagonistic roles as cell signals, in regulation of cell growth.
S1P is a ligand for plasma membrane G-protein coupled receptors (GPCRs),
 Cholesterol

Cholesterol, an important constituent of cell membranes,

has a rigid ring system and a short branched hydrocarbon tail
Cholesterol is largely hydrophobic.
But it has one polar group, a hydroxyl, making it amphipathic.
 Cholesterol
.
 Nomenclature of cholesterol
.
 Cholesterol esters

.
 Carbon numbering in cholesterol

.
 WAX
.
 WAX

Waxes are characterized by having varying mixtures of

chain length. The carboxylic acid generally even
numbers between 16 and 36 carbons atoms.
The alcohol moiety is generally between even
numbers 24 and 36 carbons. Beeswax is is a good
example.
Beeswax is produced by glands under the abdomen of
bees, which they use to construct the honeycomb. It is
recovered as a by-product when the honey is
harvested and refined. It contains a high proportion of
wax esters (35 to 80%).
61