Chapter V.

Lipids

A. Composition, Functions, and

Classification
B. Metabolism
 A. Composition, Functions,
and Classification
 Lipids are biomolecules of varying
chemical composition and may not be
described by a single type of functional
group.
 They are classified on the basis of their
solubility on non-polar solvents such as
ether, chloroform, benzene, and acetone.
 Roles / Functions of Lipids in
Biological Processes
 Energy Source
 Upon oxidation, each gram of lipid releases 9 kcal of energy (more
than twice that of carbohydrates)
 Energy Storage
 Most energy in our body is stored as triglycerides and adipocytes
 Cell Membrane Structural Components
 Phosphoglycerides, sphingolipids, and steroids make up the basic
structure of all cell membranes and function for molecular
movement and cell-to-cell communication
 Hormones
 Steroids and prostaglandins are chemical messengers that allow
body tissues to communicate with one another
 Vitamins Uptake / Absorption
 Lipid-soluble vitamins A, D, E, and K play in the major
role of critical biological processes such as vision and
blood clotting
 Vitamin Transport
 Dietary fat serves as carrier of fat-soluble vitamins.
Thus, a diet that is too low in fat can result into the
deficiency of the four lipid-soluble vitamins
 Protection
 Fats serve as shock absorber / protective layer for vital
organs
 Insulation
 Fats stored beneath the skin, called as subcutaneous fat,
serve to cushion / shield the body from extremely cold
temperatures
 Lipids
are divided into four main
groups:
 1.Fatty Acids (saturated, unsaturated)
2. Glycerides (neutral,
phosphoglycerides)
3. Nonglycerides (sphingolipids,
steroids, waxes)
4. Complex lipids (lipoproteins)
 1. Fatty Acids

 Fatty acids are long-chain monocarboxylic acids

 They generally contain an even number of
carbon atoms
 Fatty acids are classified either as saturated or
unsaturated
 Saturated fatty acids are composed of
hydrocarbons that are strictly single bonded to H
 Unsaturated fatty acids are made up of
hydrocarbons with one or more double bonds
 The general formula for saturated fatty
acid is CH3(CH2)nCOOH in which n in
biological systems is an even integer
 Eg. If n = 16, the result is an 18-carbon
saturated fatty acid commonly called as
stearic acid with formula CH3(CH2)16COOH
(known as condensed formula). It may also be
written as C17H35COOH (known as RCOOH
formula)
 Table 5.1.
Common Saturated Fatty Acids
Common IUPAC RCOOH Condensed
Name Name Formula Formula
Capric decanoic C9H19COOH CH3(CH2)8COOH
Lauric dodecanoic C11H23COOH CH3(CH2)10COOH
Myristic tetradecanoic C13H27COOH CH3(CH2)12COOH
Palmitic hexadecanoic C15H31COOH CH3(CH2)14COOH
Stearic octadecanoic C17H35COOH CH3(CH2)16COOH
Arachidic Eicosanoic C19H39COOH CH3(CH2)18COOH
 Table 5.2.
Common Unsaturated Fatty Acids
Common IUPAC RCOOH
Name Name Formula
Palmitoleic cis-9-hexadecenoic C15H29COOH
Oleic cis-9-octadecenoic C17H33COOH
Linoleic all cis-9,12,15-octadecatrienoic C17H31COOH
 Table 5.3
Melting Point of Common
Saturated and Unsaturated Fatty Acids
Saturated Melting Unsaturated Melting
Fatty Acids Point 0C Fatty Acid Point 0C
Capric 32 Palmitoleic 0
Lauric 44 Oleic 16
Myristic 54 Linoleic 5
Palmitic 63
Stearic 70
Arachidic 77
Observations on the Melting Points of
Saturated and Unsaturated Fatty Acids
 The melting points of saturated fatty acids increase with
increasing carbon number. Saturated fatty acids
containing ten or more carbons are solids at room
temperature (fats). Those which are liquid at room
temperature are called as oils.
 The melting point of a saturated fatty acid is higher than
that of an unsaturated fatty acid of the same chain
length.
 As in the case of saturated fatty acids, the melting points
of unsaturated fatty acids increase with increasing
hydrocarbon chain length.
 Percent Fatty Acid Present in Triglycerides
Fat or Oil Saturated Unsaturated
Palmitic Stearic Oleic Linoleic Other
Animal Origin
Butter 29 9 27 4 31
Lard 30 18 41 6 5
Beef 32 25 38 3 2

Vegetable Origin
Corn oil 10 4 34 48 4
Soybean 7 3 25 56 9
Peanut 7 5 60 21 7
Olive 6 4 83 7 -
Eicosanoids

 Eicosanoids are a group of hormone-like fatty acids that

are formed from precursor molecules such as
arachidonic, linoleic, and linolenic acids (essential fatty
acids)
 The name of the group is derived from the Greek word
“eikos” which means twenty, since substances belonging
to this group are all derivatives of twenty-carbon fatty
acids; they also contain more than one double bonds
 Eicosanoids include prostaglandins, leukotrienes, and
thromboxanes
Prostaglandins
 Originally isolated from the seminal fluid coming from the
prostate gland
 Consists of a 20-carbon skeleton that contains a 5-carbon
ring
 Involved in the following processes
 Stimulation of smooth muscles (eg. uterine contractions)
 Regulation of steroid biosynthesis
 Inhibition of gastric secretion
 Inhibition of hormone-sensitive lipases
 Inhibition of platelet aggregation
 Regulation of nerve transmission
 Sensitization to pain
 Mediation of the inflammatory response
Leukotrienes

 A group of fatty acids produced by certain white blood

cells and promotes either the constriction or dilation of
bronchi
Thromboxanes

 A group of fatty acids produced by platelets in the blood

and promote either constriction of the blood vessels and
aggregation of platelets or dilation of blood vessels and
prevention of untimely platelet aggregation
 2. Glycerides

 Glycerides are lipid esters that contain the

glycerol molecule and fatty acids
 Subdivided into two classes- the neutral
glycerides and the phosphoglycerides
Neutral glycerides

 Non-ionic, non-polar, and uncharged

 Occur as mono-, di-, and triglycerides
 Triglycerides are considered as the most
important of the neutral glycerides and are the
major component of fat cells
 Consists of a glycerol backbone joined to three fatty
units through ester bond
 It mainly functions for storage of energy and may lead
to the formation of adipose tissues
Phosphoglycerides

 Glycerides that contain a polar phosphate group

and non-polar fatty acid tails
 The phosphate / phosphoryl group ionizes in
solution, making the lipid charged
 Also known as phospholipids and are the most
abundant membrane lipids in the cell
 Eg. Phosphatidylcholine (lecithin) which is
amphiphatic and is also found in eggyolks and soy
beans; used as emulsifying agent in ice creams – aids
in the suspension of triglycerides in water
 3. Non-glyceride lipids

 Sphingolipids
 Not derived from glycerol
 Amphiphatic and is also a membrane lipid
 Derived from sphingosine, a nitrogen-containing
alcohol
 Eg. Sphingomyelins – insulate nerve tissue and
enable proper cerebral function and nerve
transmission
 Eg. Glycosphingolipid – found in membranes of
macrophages and brain cells
 Steroids
 Members of a large, diverse collection of lipids also known
as isoprenoids which are built from one or more 5-carbon
units known as isoprene
 Eg. Cholesterol – found in the membrane of most animal
cells, amphiphatic, and is involved in the regulation of the
fluidity of the membrane; increased concentration is
associated with atherosclerosis (hardening of the arteries)
 Plays an important role in the reproductive cycle (leads
on the formation of sex hormones such as progesterone,
testosterone)
 Medically used as contraceptive by inducing false
pregnancy
 Eg. Bile salts – cholesterol derivatives that are synthesized
in the liver and stored in the gall bladder
 Eg. Cortisone – involved in carbohydrate metabolism, and
in the treatment of certain diseases such as arthritis,
asthma, and GI disorders but may produce side effects
such as osteoporosis, peptic ulcers, headaches, and
convulsions
General structure of a steroid
 Waxes
 Very varied in sources and composition but mostly
with long chained fatty acids esterified to a long chain
alcohol
 Eg, paraffin wax – composed of a mixture of solid
hydrocarbons
 With extremely hydrophobic tails so that they are
insoluble in water
 Eg. Lanolin – protective coating for hair and skin
 Eg. Carnauba wax – used in automobile polishing
wax
 4. Complex Lipids

 Lipids that are bonded to other molecules

 The most common and important complex lipids are
plasma lipoproteins, which are responsible for the
transport of other lipids in the body
 Lipoprotein particles consist of a core of hydrophobic
lipids surrounded by amphiphatic proteins,
phospholipids, and cholesterol
 Four major classes
 Chylomicrons
 Very low-density lipoproteins (VLDL)
 Low-density lipoproteins (LDL)
 High-density lipoproteins (HDL)
Chylomicrons

 Density is less than 0.95 g / mL

 Carry triglycerides from the intestines to the
other tissues
Very low density lipoproteins

 Density is 0.95 – 1.019 g / mL

 The form of triglycerides which are
synthesized in the liver
 Carry energy-rich lipid molecules either to
tissues requiring energy or to adipose
tissues for storage
Low-density lipoproteins

 Density is 1.019 – 1.063 g / mL

 Richest in cholesterol, frequently carrying
40% of the plasma cholesterol
 They carry cholesterol from the liver to
peripheral tissues and help regulate
cholesterol levels in those tissue
 Mechanism of LDL uptake by the cell:
 LDL enters the cell by first binding to LDL receptors
embedded in the cell membrane
 The LDL-receptor complex is then uptaken by the cell
through a process called receptor-mediated endocytosis
 The entire LDL contained in the membrane portion will
be pulled inward until this membrane pinches away and
form a vesicle / endosome
 The endosome carrying the LDL then fuses with a
lysosome that secretes lysosyme which in turn digests
the complex and enables the release of the cholesterol
 When cholesterol concentration in the cell becomes
high, further cholesterol uptake is inhibited
 Hypercholesterolemia – a genetic disorder that
consists of the inability of the cell to uptake cholesterol
due to lack of gene that encodes for the synthesis of
LDL receptors. This results in the accumulation of
cholesterol in the plasma which may then lead to
atherosclerosis (hardening of the arteries)
High-density lipoproteins (HDL)
 Density is 1.063 – 1.210 g / mL
 They are bound to plasma cholesterol and transport
cholesterol in peripheral tissues as well as to the liver
 The liver uptakes these cholesterol through its liver
lipoprotein receptor molecules
 Once inside the liver, some of the cholesterol is used
for bile synthesis and secreted into the intestines, from
which, it is excreted
 HDL therefore ensures low concentrations of
cholesterol in the blood plasma
 Medical studies have revealed that a person with the
most liver lipoprotein receptors will be the least
affected by a high-cholesterol diet and has the least
likelihood of developing atherosclerosis
 In relation, people whose diet is high in saturated fats
have been found out to have high levels of cholesterol
in the blood while a diet high in unsaturated fatty acids
result in decreased cholesterol levels, a decrease in
LDL, and an increase in HDL levels.
 Thus, the current dietary recommendations include a
low-fat diet and the substitution of saturated / animal
fats with vegetable / unsaturated oils.
 B. Metabolism

 Lipid metabolism in humans consists of

 Digestion and Absorption of Dietary
Triglycerides
 Lipid Storage
 Fatty Acid Degradation
Digestion and Absorption
of Dietary Triglycerides
 Triglycerides are initially, and to a very limited
extent, become degraded by water soluble
lipases
 Most dietary fat arrives at duodenum, the first
part of the small intestine, in the form of fat
globules
 The fat globules stimulate the secretion of bile
(micelles of lecithin) from the gall bladder
 Bile salts (cholate and
chenodeoxycholate) emulsify the fat globules
into tiny droplets, increasing the molecules’
surface area, allowing them to be more easily
hydrolyzed by lipases
 A protein called colipase also binds to the
surface of the lipid droplets, helping the lipase
to stick to the surface of the molecule and
thereby hydrolyzing the ester bonds between
the glycerol and the fatty acids in a triglyceride
 In such action, two of the three fatty acids are
liberated and the monoglycerides and free fatty
acids produced mix freely with the micelles of
bile which are then readily absorbed through
the membranes of the intestinal epithelial cells
 Inside the epithelial cells, the monoglycerides and
fatty acids are then reassembled into triglycerides
and are combined with proteins to form chylomicrons
 The chylomicrons are secreted into small
lymphatic vessels and eventually arrive into the
bloodstream
 In the bloodstream, the triglycerides are once again
hydrolyzed to produce glycerol and free fatty acids
that are then absorbed by the cells
 If the body needs energy, these molecules are
degraded to produce ATP
 If the body does not need additional energy source
yet, these energy rich molecules are then stored
Lipid Storage
 Fatty acids are stored in the form of triglycerides
which are stored as fat droplets in the cytoplasm of
adipocytes that make up adipose tissues
 Each adipocyte contains a large fat droplet that
accounts for nearly the entire volume of the cell
 Other cells, such as those of the cardiac muscle,
contain few small fat droplets which are surrounded
by the mitochondria so that they may be easily
oxidized when additional energy source would be
needed
 Completely oxidized fatty acids release much more
energy than the oxidation of the same amount of
glycogen
Fatty Acid Degradation
 Occurs via the removal of two carbon fragments
(acetyl CoA) from the carboxyl end of the fatty
acid
 Referred to as β-oxidation which consists of
reactions with over-all form similar to the last
four reactions of the citric acid cycle
 Each round releases acetyl CoA and returns a
fatty acyl CoA molecule that has two fewer
carbons
 One molecule of FADH2 equivalent to 2 ATP
molecules, and one molecule of NADH,
equivalent to 3 ATP molecules are produced for
each cycle of β-oxidation
The Reactions of β-oxidation

 Activation
 Oxidation / dehydrogenation of fatty acid
 Hydration
 Oxidation / dehydrogenation of the
hydroxyl group of β-carbon
 Thiolysis
Activation

 Fatty acid reacts with coenzyme A,

utilizing ATP, and producing fatty acyl
CoA, through the formation of a thioester
bond
Oxidation / dehydrogenation
of fatty acid

 Fatty acyl CoA is oxidized /

dehydrogenated leading into the reduction
of FAD into FADH2 and resulting into the
formation of a carbon-carbon double bond
 FADH2 undergoes oxidative
phosphorylation yielding ATP molecules
Hydration

 The double bond in the fatty acyl CoA

reacts with water, removing the double
bond and introducing OH in the
hydrocarbon length of the fatty acyl CoA
Oxidation / dehydrogenation
of the hydroxyl group of β-carbon

 The hydroxyl group of the β-carbon is

dehydrogenated leading into the reduction
of NAD+ into NADH and resulting into an
oxidized fatty acyl CoA.
 NADH undergoes oxidative
phosphorylation to form 3 ATP molecules
Thiolysis

 Catalyzed by the enzyme thiolase, acetyl

CoA is cleaved from the fatty acid,
releasing the acetyl CoA and the fatty acyl
CoA
 The fatty acyl CoA is further oxidized by
cycling through reactions 2 to 5 until the
fatty acid carbon chain is completely
degraded to acetyl CoA
Summary of the no. of ATP molecules
produced in the complete oxidation of
stearic (octadecanoic)Acid
 Step 1 - 2 ATP
 Steps 2 – 5
 8 FADH2 x 2 ATP / FADH2 16 ATP
 8 NADH x 3 ATP / NADH 24 ATP
 9 acetyl CoA (to citric acid cycle)
 9 x 1 GTP x 1 ATP / GTP 9 ATP
 9 x 3 NADH x 3 ATP / NADH 81 ATP
 9 x 1 FADH2 x 2 ATP / FADH2 18 ATP
146 ATP