This tackles the topic on Lipids, generally. This include its uses, structures, metabolism and Chemical reactions involved with it. This is a great help for learners in Junior High School, senior high school and those who are majoring in Science.

1. Structure and Chemical
Reactions of LIPIDS
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2. LIPID STRUCTURE and Function
LIPIDS are organic compounds that are insoluble, or
only slightly soluble, in water and are extractable in
nonpolar solvents, such as chloroform.
Saponifiable lipids yield the salts of fatty acids when
they are hydrolyzed by heat and alkali; nonsaponifiable
lipids are not hydrolyzed by heat and alkali; they are the
neutral fats, such as cholesterol.
Lipids serve many physiologic functions:
a. As stored fat, they provide energy reserves.

3. LIPID STRUCTURE and Function
b. As important components of both extracellular and
intracellular membranes, they help separate cells
and the organelles within the cells.
c. As steroids, they appear in the body as cholesterol
(an important component of cell membranes) and
steroid hormones, such as testosterone and
estradiol.
d. As signal transducers, they mediate the response
from an extracellular signal into an intracellular
biochemical event.

4. LIPID STRUCTURE and Function
Fatty acids are energy reserves; the complete
oxidation of fatty acids to CO2 and water generates
adenosine triphosphate (ATP).
a. Besides being a source of energy reserves; fatty
acids are components of other lipids, including
triacylglycerols, phospholipids, and glycolipids;
derivatives of fatty acids are hormones (such as
prostaglandins) and intracellular signal
transducers (such as diocylglycerol).
b. Structurally, a fatty acid is a long hydrocarbon chain
with a terminal carboxyl group, having the general
structure CH3(CH2)n – COOH.

5. LIPID STRUCTURE and Function
c. Most higher plants and animals have fatty acids
with an even number of carbon atoms (usually
between 14 and 24).
d. In labeling the carbons of a fatty acid, the carbon
adjacent to the carboxyl carbon is called the α
carbon and the next carbon is the β carbon;
alternatively, carbon atoms may be numbered,
beginning with the carboxyl C as C-1.
e. Fatty acids are named either by naming the parent
hydrocarbon and adding the suffix –oate or by
some other common name.

6. LIPID STRUCTURE and Function
f. Fatty acids are either saturated (containing no double bonds) or unsaturated
(containing one or more double bonds, usually in the cis configuration); C16:0 denotes
a 16 – carbon saturated fatty acid, where 16 is the number of C atoms and 0 is the
number of double bonds; a 16 – carbon fatty acid with one double bond between
carbon 9 and 10 is written as either C16:1Δ9 or C16:1(9), where Δ9 or (9) denotes the
position of the unsaturated bond.

7. LIPID STRUCTURE and Function
Triacylglycerols, also called triglycerides, are the storage
form of fatty acids; they are located mainly in the
cytoplasm of adipose cells and liver cells.
a. Structurally, a triacylglycerol is three (tri) fatty acids
linked by their acyl groups in an ester linkage to
glycerol.
b. The carbon atoms of glycerol are numbered as
stereospecific numbers (sn) 1, 2, and 3 starting from
the top when glycerol is drawn in a Fischer projection
with the C-2 hydroxyl group projecting to the left.
c. If the fatty acid at C-1 differs from that C-3, then C-2 is
asymmetric; naturally occurring triacylglycerols have
the L configuration.

8. LIPID STRUCTURE and Function
Glycerophospholipids are sn glycerol 3 – phosphate with
fatty acids esterified at the C-1 and C-2 positions of
glycerol and with various other groups derived from
polar alcohols esterified at the phosphate group on C-3.
a. When only one fatty acid is esterified to glycerol 3-
phosphate sn 1 or sn 2, lysophosphatidate is formed;
glycerophospholipid is formed when a polar alcohol is
esterified to the phosphate group of phosphatidate.
b. Glycerophospholipids vary depending upon the fatty
acids esterified to the glycerol backbone and the
group esterified to the phosphate.
c. The fatty acids at C-1 are usually saturated, while
those at C-2 are usually unsaturated.

9. LIPID STRUCTURE and Function
d. Phosphatidylinositol, so named because the
carbohydrate inositol is bound to phosphatidate,
generates important signal transducers; the
phospholipids phosphatidylcholine,
phosphatidylethanolamine, and phosphatidylserine
are all named for the X group attached to the
phosphate of phosphatidate.
e. Glycerophospholipids are amphipathic because of
their polar “head group” (charged phosphate or
substituents bound to phosphate) and their two
nonpolar fatty acid “tail groups.”

10. LIPID STRUCTURE and Function
Sphingolipids contain sphingosine as the backbone
to which other groups are attached.
a. Sphingosine is a C18 amino alcohol with a single
unsaturated bond in the C18 chain.
b. Fatty acids form an amide linkage with the
amino group of sphingosine, forming a
ceramide.
c. Phosphate can be linked to the primary alcohol
of a ceramide to form a sphingophospholipid;
when phosphocholine is attached, the
compound formed is sphingomyelin, which is
the most abundant sphingolipid and the only
sphingolipid found in membranes.

11. LIPID STRUCTURE and Function
Glycolipids contain a carbohydrate molecule bound at
sn 3 to a lipid alcohol group through a glycosidic bond.
a. Glycolipids are classified as either glycerides (if
glycerol is the backbone) or glycosphingolipids (if
sphingosine is the backbone); most naturally
occurring glycolipids are glycosphingolipids.
b. Two important categories of glycosphingolipids are
cerebrosides and gangliosides; cerebrosides are
ceramides with either glucose or galactose attached
to a primary sphingosine hydroxyl group;
gangliosides are complex cerebrosides that contain
many carbohydrates (oligosaccharides), linked by a
glucose residue, attached to sphingosine.

12. LIPID STRUCTURE and Function
Steroids include various compounds with the same
general structure: a fused – ring system consisting
of three six – membered rings plus one five –
membered ring.
a. The most important steroids include sex
hormones and cholesterol.
b. Cholesterol, an important component of
membranes in animals, is not present in plants.
c. Structurally, cholesterol contains 27 carbon
atoms in four fused rings, with an eight –
member branched hydrocarbon chain at C-17, a
hydroxyl group at C-3, two non-ring methyl
groups designated C-18 and C-19 and an
unsaturation between C-5 and C-6.

13. LIPID STRUCTURE and Function
d. Cholesterol is a precursor of the steroid
hormones pregnenolone (C21) and
progestogens (C21); progestogens in turn are
precursors of glucocorticoids (C21),
mineralocorticoids (C21), and androgens (C19);
androgens are precursors of estrogens (C18).
e. Bile acids, which are polar derivatives of
cholesterol, are products of cholesterol
catabolism; two bile acids are glycocholate and
taurocholate.
f. Bile acids are synthesized in the liver, stored
and concentrated in the gallbladder, and
released into the small intestine to solubilize
dietary lipids.

14. LIPID STRUCTURE and Function

15. MEMBRANES
All cells have a cell membrane (also known as
the plasma membrane); in addition, eukaryotic
cells have membranes that encloses their
various organelles.
Membranes are dynamic structures that control
the space they enclose by selectively excluding
or including certain molecules.
a. Membranes may contain biologically active
molecules that are receptors for messenger
molecules, such as hormones and proteins.
b. Membranes may contain molecules that act
as signal transducers and other molecules
that serve as markers differentiating one cell
type from another.

16. MEMBRANES
Lipids provide the structural components of
membranes and account for the hydrophobicity
of membranes; phospholipids
(glycerophospholipids and
sphingophospholipids) and cholesterol are the
major lipid components of the membranes.
Proteins constitute from 20% to 80% of
membranes, depending upon the particular
membrane; intracellular (organelle)
membranes have a higher protein content than
cellular membranes.
Carbohydrates, as glycoproteins or glycolipids,
are a minor component of membranes.

17. MEMBRANES
Membrane phospholipids are arranged in a bilayer structure.
a. The polar head groups constitute the two outer surfaces
exposed to the aqueous environment, one facing the
exterior of the cell or organelle and the other facing the
interior.
b. The fatty acid tail groups project inward and form a
nonpolar environment shielded from water.
Membranes are fluid rather than static, a characteristic that
permits a cell or organelle to both adjust its shape and move;
the degree of fluidity in a membrane depends on the type of
fatty acids in the phospholipid bilayer.
a. Long – chain saturated fatty acids form an extended, more
rigid structure.
b. Short – chain fatty acids and unsaturated fatty acids
enhance membrane fluidity because the hydrocarbon tail
of an unsaturated fatty acids bends at the double bond,
allowing less ordered (more fluid) structure.

18. MEMBRANES
Membranes are asymmetric.
a. The carbohydrate residues of glycolipids and glycoproteins are
oriented so that they project to the exterior surface of the
plasma membrane.
b. Proteins in the membrane may move from location within the
membrane.
c. Peripheral, or extrinsic, proteins are on the membrane surface
and are easily dissociated from the membrane; integral or
intrinsic, proteins are difficult to dissociate from the
membrane; they are embedded within the membrane and may
project partially into the lipid bilayer or completely transverse
the membrane.
Membranes use noncovalent molecular interactions to achieve and
maintain their structure.
a. The nonpolar fatty acid tails are hydrophobic (repelled by
water) and attracted to each other by van der Waals attractive
forces.
b. The polar head groups are attracted to water through H-
bonding and ionic interactions with water molecules.

19. MEMBRANES
The fluid mosaic model of membrane accounts for the
mobility of the membrane proteins and the various degrees
of fluidity observed in membranes.
a. Membrane lipids serve two main functions: they provide a
permeability barrier, especially against hydrophilic
molecules, and they accommodate integral proteins (the
conformational bend produced by an unsaturated fatty
acid may permit protein insertion).
b. Both lipids and proteins are free to move and diffuse
within the membrane.
Molecules can move through a membrane by a variety of
mechanisms; the type of transport depends on the specific
molecule and the specific membrane.

20. MEMBRANES
a. In passive transport, a molecule moves across a
membrane from a region of higher concentration to
a region of lower concentration; because the
molecule is not moving against a concentration
gradient, the cell expends no energy.
(1) Simple diffusion is a type of passive transport in
which the molecule moves through an opening or
pore in the membrane following the concentration
gradient; small molecules, such as water or oxygen,
move directly through cell membranes via simple
diffusion.
(2)In facilitated diffusion, the molecule to be
transported binds to a carrier protein, which then
changes conformation to move the molecule across
the membrane.

21. MEMBRANES
b. In active transport, a molecule moves across the
membrane from a region of low concentration to a
region of high concentration; moving a molecule
against its concentration gradient requires energy
expenditure.
(1)The active transport of Na+1 to the outside of a cell
and K+1 inside of the cell are examples of ion
movement against the normal concentration
gradient.
(2)To facilitate the movement of these ions, a single
type of membrane protein both hydrolyzes ATP for
energy and transports the ion against its
concentration gradient; the ion movement
performed by this membrane protein is called the
sodium – potassium ion pump.

22. LIPID
METABOLISM
Lipids or their components
molecules are transported
throughout the body in
various forms.
a. Lipids can be found in
blood plasma complexed to
a various proteins (plasma
lipoproteins), such as
chylomicrons, very – low
density lipoproteins
(VLDL), low-density
lipoproteins (LDL) and
high-density lipoproteins.
b. Fatty acids can be bound to
plasma protein albumin.
The complete oxidation of a
fatty acid yields approximately
twice as much as ATP than
complete oxidation of a
carbohydrate; in animals, stored
fat contains much reservoir of
energy than a comparable
weight of stored glycogen.
Catabolism of fatty acids from
triacylglycerols provide the bulk
of energy animals extract from
lipids.
a. Fatty acids are catabolized
through a process called β
oxidation, so named because
oxidation occurs at β carbon.

23. LIPID
METABOLISM
b. Most of the reactions of β
oxidation occur in the
mitochondrial matrix; only
the initial reaction (the
activation of fatty acid)
occurs in the cytosol.
Catabolism of Fatty Acids
Triacylglycerols, stored in the
cytoplasm of adipose and liver
cells, are first hydrolyzed into
fatty acids and glycerol
through the action of specific
lipases that hydrolyze bonds at
sn1, sn2, and sn3 position of
triacylglycerols;
The glycerol released is
converted ultimately to
glyceraldehyde 3-phosphate,
which may be used in either
glycolysis or
gluconeogenesis. Fatty acids
released by lipases are first
“activated” by forming a
thioester bond with coenzyme A
(CoA) forming acyl CoA; acyl
CoA synthetase catalyzes this
reaction using two high –
energy bonds from hydrolysis of
ATP to adenosine
monophosphate (AMP) and
inorganic phosphate(PPi).

24. LIPID
METABOLISM
a. The activated fatty
acids are transported
from the cytosol
across the outer
mitochondrial
membrane and into
the intermembrane
space.
b. Carnitine, a
derivative of the
amino acid lysine,
transports the fatty
acids across the
mitochondrial
membrane and into
the matrix.
(1) At the outer surface of the
inner mitochondrial
membrane, the fatty acid
releases CoA, forms a bond
with carnitine, and crosses
the inner surface of the
inner mitochondrial
membrane as acyl
carnitine.
(2) On the matrix side of the
inner mitochondrial
membrane, the fatty acid
once again complexes with
another CoA to re-form
acyl CoA and releases
carnitine

25. LIPID METABOLISM
(3) The enzymes carnitine
acyltransferase I (on the outer
surface of the inner
mitochondrial membrane) and
carnitine acyltransferase II (on
the matrix side of the inner
mitochondrial membrane)
catalyze these reactions.
Inside the mitochondrial
matrix, the fatty acid is
catabolized in an energy-
producing process called β
oxidation.

26. LIPID METABOLISM
Inside the mitochondrial matrix, the fatty acid is
catabolized in an energy – producing process called β
oxidation.
a. The single bond between the α and the β carbon of acyl
CoA is oxidized to a trans double bond, forming β-enoyl
CoA; acyl CoA dehydrogenase, the enzyme that
catalyzes this reaction, requires oxidized flavin
adenine dinucleotide (FAD) as coenzyme; FAD is
reduced to FADH2 and then enters the respiratory
chain to produce 2 ATP molecules via oxidative
phosphorylation.
b. A molecule of water is added to the double bond,
forming β-L-hydroxyacyl CoA; the enzyme enoyl CoA
hydratase catalyzes the reaction.

27. LIPID METABOLISM
c. The new hydroxyl group of β-L-hydroxyacyl CoA is
oxidized to a carbonyl group, forming β-ketoacyl CoA; this
reaction catalyzed by β-hydroacyl CoA dehydrogenase
requires nicotinamide adenne dinucleotide (NAD+) as a
cofactor; NAD+ is reduced to NADH and then enters the
respiratory chain, producing 3 ATP molecules via
oxidative phosphorylation.
d. The enzyme β-ketothiolase, also called acetyl CoA
acetyltransferase or thiolase, catalyzes the cleavage of β-
ketoacyl CoA; this reaction requires a molecule of acetyl
CoA and produces acetyl CoA and acyl CoA that is two
carbons shorter than the original fatty acid molecule.
e. The shortened fatty acid chain repeats the β-oxidation
pathway until the fatty acid is completely oxidized to
acetyl CoA.

28. LIPID METABOLISM
Each cycle of β oxidation (except the last) produces one
molecule each of FADH2, NADH + H+1, and acetyl CoA; the
last cycle produces two molecules of CoA because the four-
carbon fatty acid is cleaved in half.
As an example, the catabolism of palmitate (C16:0)
generates 129 molecules of ATP as it is degraded in seven
rounds of β oxidation.
a. Eight molecules of acetyl CoA are produced directly
through β oxidation.
b. In the tricarboxylic acid (TCA) cycle and respiratory
chain, each acetyl CoA generates 12 molecules of ATP;
therefore 8 x 12 = 96 molecules of ATP are produced.

29. LIPID METABOLISM
c. Seven molecules of FADH2 are produced during β
oxidation of the entire palmitate molecule; in the
respiratory chain each FADH2 generates two molecules of
ATP; therefore 7 X 2 = 14 molecules of ATP are produced
from FADH2.
d. Seven molecules of NADH are produced during β
oxidation of the entire palmitate molecule; in the
respiratory chain each NADH generates 3 molecules of
ATP; therefore 7 x 3 = 21 molecules of ATP are produced.
e. Two high – energy bonds (ATP converted to AMP) are
expended in activation of fatty acid; therefore 96 + 14 +
21 – 2 = 129 molecules of ATP are produced by the
oxidation of one palmitate molecule.

30. LIPID METABOLISM
Catabolism of unsaturated fatty acid requires additional
enzymes.
a. Activation of unsaturated fatty acids and their
transport into mitochondria occur by the same
processes as for saturated fatty acids.
b. β oxidation proceeds as for saturated fatty acids until
the site of unsaturation is reached;
c. An isomerase then shifts the unsaturation to the
adjacent carbon and also converts it from a cis to trans
configuration.
d. The trans configuration of the double bond is a normal
substrate for the enzyme enoyl CoA hydratase and β
oxidation proceeds normally.

31. LIPID METABOLISM
e. If a fatty acid containing more than one unsaturated
(polyunsaturated) bond is oxidized, epimerase is also
needed.
In certain situations, acetyl CoA is used preferentially over
glucose as an energy source; during fasting and starvation, fat
is mobilized from adipose tissue and metabolized for energy;
in diabetes, glucose is not available for glycolysis because a
shortage of insulin prevents glucose entry into cells.
a. Both fasting and diabetes cause acetyl CoA (from the β
oxidation of fatty acids) to be used preferentially over
glucose as an energy source; when acetyl CoA is the
primary fuel oxidized; ketone bodies are produced.

32. LIPID METABOLISM
b. Acetyl CoA is present in the higher amounts than
oxoacetate, the compound it initially joins in the TCA
cycle; excess acetyl CoA forms acetoacetate, which is
spontaneously decarboxylated to acetone, and β-
hydroxybutyrate; these three compounds are called
ketone bodies.
c. Acetoacetate and β-hydroxybutyrate, previously
thought to be nonfunctional byproducts, are used as
energy sources by the heart and, in starvation or
diabetes, by the brain.
In normal, healthy states, any acetyl CoA not needed for
immediate energy production is used to synthesize fatty
acids, which are storage forms of energy for later use.

33. LIPID METABOLISM
Fatty Acid Synthesis
Fatty acid synthesis takes place in the cytosol of liver cells; two
preliminary steps are necessary before fatty acid synthesis can
begin.
a. Fatty acid synthesis begins with acetyl CoA in the cytosol;
acetyl CoA must somehow leave the mitochondria and be
transferred to the cytosol.
b. Acetyl CoA is produced in the mitochondria, both from β
oxidation of fatty acids and from pyruvate through the action
of the pyruvate dehydrogenase complex.
c. Acetyl CoA does not readily cross the mitochondrial
membrane; instead, it reacts with oxaloacetate to form citrate,
catalyzed by citrate synthase (a normal step in the TCA cycle);
this is the first preliminary step to fatty acid synthesis.

34. LIPID METABOLISM
d. Citrate is transported from the mitochondria into the cytosol
where it crosses the outer mitochondrial membrane and reacts
with CoA and ATP, forming acetyl CoA, oxaloacetate, adenosine
diphosphate (ADP), and inorganic phosphate (Pi); this reaction
is catalyzed by citrate lyase.
e. CO2, in the form of bicarbonate (HCO3
—1) is added to acetyl
CoA to form malonyl CoA; this reaction, catalyzed by acetyl CoA
carboxylase, is the second primary step to fatty acid synthesis.
(1)This reaction, the commitment step and the rate limiting step
of fatty acid synthesis, requires ATP, which is hydrolyzed to
ADP and Pi; manganese ions (Mn+2) and biotin are cofactors.
(2)Acetyl CoA carboxylase is allosterically activated by increased
concentrations of citrate and isocitrate, TCA cycle components
that signal that energy is available to be stored as fatty acids.

35. LIPID METABOLISM
(3) Acetyl CoA carboxylase is allosterically inhibited by the
ultimate product of fatty acid synthesis, palmitoyl CoA.
f. The synthesis of fatty acids is the successive addition of two –
carbon units to the malonyl CoA starting molecule; the usual
end product of fatty acid synthesis is palmitate, C16.
The reactions that convert malonyl CoA to a fatty acid are
catalyzed by fatty acid synthase, which in bacteria is a complex of
different proteins; in higher organisms, fatty acid synthase is a
large multienzyme complex contained in one protein.
a. Intermediate compounds in fatty acid synthesis are bound to
an acyl carrier protein (ACP), similar to the linkage of
intermediate compounds to CoA in fatty acid catabolism.

36. LIPID METABOLISM
b. To begin the reaction, acetyl CoA binds to a part of ACP; the
bonding of acetyl CoA to ACP to form acetyl ACP is catalyzed by
ACP acetyltransferase.
c. Malonyl, as malonyl CoA, is transferred to a different site on
the ACP forming malonyl-ACP and CoA; the reaction is
catalyzed by ACP-malonyltransferase.
d. The enzyme β-ketoacyl-ACP-synthase catalyzes the
condensation between one molecule each of malonyl-ACP and
acetyl-ACP, to form one molecule of acetoacetyl-ACP and
release one molecule each of ACP and CO2; the carbons from
the acetyl-ACP are always the two terminal carbons of the
growing fatty acid chain.

37. LIPID METABOLISM
e. In the first of two reduction reactions, acetoacetyl-ACP is
reduced to β-hydroxybutyryl-ACP; the reaction, catalyzed by
β-ketoacyl-ACP-reductase, requires the cofactor reduced
nicotinamide adenine dinucleotide phosphate (NADPH) and
H+1, which is subsequaently oxidized to NADP+.
f. β-hydroxybutyryl-ACP is dehydrated to crotonyl-ACP in a
reaction catalyzed by β-hydroxyacyl-ACP-dehydratase.
g. In the second reduction reaction, crotonyl-ACP is reduced to
butyryl-ACP; this reaction, catalyzed by β-enoyl-ACP-
reductase, requires the cofactor NADPH, which is
subsequently oxidized to NADP+.

38. LIPID METABOLISM
In subsequent rounds of fatty acid synthesis, two-carbon units that
are derived from malonyl-ACP (a three-carbon compound) are added
to the growing fatty acid chain until after seven cycles, the sixteen-
carbon compound palmitoyl-ACP deacylase and may be transferred
to CoA.
Fatty acids containing an odd number of carbon atoms are
synthesized by the same reactions; however, propionyl CoA (a three-
carbon compound) is used in place of acetyl CoA for condensation
with malonyl-ACP.
a. The enzyme ACP-acyltransferase can transfer any acyl groups,
not just acetyl groups.
b. The first condensation reaction yields a five – carbon
intermediate and CO2.
Production of fatty acids longer than palmitate involves the addition
of acetyl units; malonyl CoA is the donor of the two-carbon units.

39. LIPID METABOLISM
Production of unsaturated fatty acids occurs in the mitochondria
and requires NADH, O2, and cytochrome b5.
Humans cannot synthesize essential fatty acids and must therefore
obtain them from the diet.
a. Linoleate (C18:2), linolenate (C18:3), and arachidonate (C20:4) are
essential fatty acids.
b. Linoleate is considered the only true essential fatty acid,
because linolenate and arachidonate can be produced from it.

40. LIPID METABOLISM
Cholesterol Synthesis
Cholesterol synthesis occurs in the cytosol of cells; all
27 carbon atoms in cholesterol are derived from
acetate, in the form of acetyl CoA.
The two-carbon compound acetyl CoA is converted
into the five-carbon (C5) compound isopentenyl
pyrophosphate.
a. Acetyl CoA is first complexed with acetoacetyl
CoA, forming the C5 compound 3 – hydroxy-3-
methylglutaryl (HMG) CoA.
b. HMG CoA is converted to mevalonate by HMG CoA
reductase, this is the commitment step of
cholesterol synthesis.

41. LIPID METABOLISM
c. In three reactions that each use ATP, mevalonate is
converted into isopentynyl pyrophosphate, a C5
compound.
d. Isopentynyl pyrophosphate isomerizes to
dimethylallyl pyrophosphate; two molecules of
dimethylallyl pyrophosphate condense to form the
C10 compound geranyl pyrophosphate.
e. Geranyl pyrophosphate condenses with one
molecule of dimethylallyl pyrophosphate to form
the C15 compound farnesyl pyrophosphate.
f. Two molecules of farnesyl pyrophosphate
condense to form the C30 compound squalene.
g. Squalene is oxidized, forming an epoxide, which
cyclizes to form lanosterol.
h. Three carbon atoms are removed from lanosterol,
forming the C27 compound cholesterol.

42. 1. Differentiate saturated and
unsaturated fatty acids.
2. List the different types of lipids and
explain how each type is being
structurally formed.
3. Describe the function of lipids in the
structure of the cell membrane.
4. Trace reaction mechanisms of β
oxidation of fatty acids, fatty acid
synthesis and cholesterol synthesis.

43. Reference: