Lipid Metabolism

By Fadilah Nor Laili Lutfia, M.Biotech.

Lipid
• The lipids are a heterogeneous group of compounds, including fats,
oils, steroids, waxes, and related compounds.

(1) relatively insoluble in water and

(2) soluble in nonpolar solvents such as ether and chloroform.
Lipid
Lipids are important dietary
constituents not only because
of their high energy value but
also because of the fat-soluble
vitamins and the essential
fatty acids contained in the fat
of natural foods.
• Fatty acids occur mainly as esters in natural fats and oils but do occur in the
unesterified form as free fatty acids, found in the plasma.
• Fatty acids that occur in natural fats are usually straight-chain derivatives
containing an even number of carbon atoms. The chain may be saturated
(containing no double bonds) or unsaturated (containing one or more
double bonds).
• The most frequently used systematic nomenclature names the fatty acid
after the hydrocarbon with the same number and arrangement of carbon
atoms, with -oic being substituted for the final.
• Thus, saturated acids end in -anoic, eg, octanoic acid, and unsaturated
acids with double bonds end in -enoic, eg, octadecenoic acid (oleic acid)
LIPIDS ARE CLASSIFIED AS SIMPLE OR
COMPLEX
1. Simple lipids: Esters of fatty acids with various alcohols.

a. Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state.
b. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols.

2. Complex lipids: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid.

a. Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue.
b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and carbohydrate.
c. Other complex lipids: Lipids such as sulfolipids and aminolipids. Lipoproteins may also be placed in this
category.

3. Precursor and derived lipids: These include fatty acids, glycerol, steroids, other alcohols, fatty
aldehydes, and ketone bodies, hydrocarbons, lipid-soluble vitamins, and hormones.
1. TRIACYLGLYCEROLS (TRIGLYCERIDES)* ARE THE MAIN
STORAGE FORMS OF FATTY ACIDS

• The simplest lipids constructed from fatty acids are the

triacylglycerols, also referred to as triglycerides.

• Triacylglycerols are composed of three fatty acids each in ester

linkage with a single glycerol
• In most eukaryotic cells,
triacylglycerols form an oily
droplets in the aqueous cytosol,
serving as depots of metabolic fuel.
• In vertebrates, specialized cells
called adipocytes, or fat cells, store
large amounts of triacylglycerols
• Triacylglycerols are also stored as
oils in the seeds of many types of
plants, providing energy
• In some animals, triacylglycerols stored under the skin serve not only
as energy stores but as insulation against low temperatures.
• Most natural fats, such as those in vegetable oils, dairy products, and
animal fat, are complex mixtures of simple and mixed triacylglycerols.
These contain a variety of fatty acids differing in chain length and
degree of saturation
• Vegetable oils such as corn (maize) and olive oil are composed largely
of triacylglycerols with unsaturated fatty acids and thus are liquids at
room temperature.
2. STRUCTURAL LIPIDS IN MEMBRANES

• The biological membranes is a double layer of lipids. Membrane lipids

are amphipathic: one end of the molecule is hydrophobic, the other
hydrophilic.
3. LIPIDS AS SIGNALS, COFACTORS, AND PIGMENTS

1. Storage lipids (80% of the mass of an adipocyte) : lipid fuels are

stored until oxidized by enzymes
2. Structural lipids (5-10% of the dry mass of most cells) : impermeable
barriers around cells and cellular compartments

smaller amounts, have active

roles in the metabolic traffic as
metabolites and messengers
• Prostaglandins (PG) contain a five-carbon ring originating from the
chain of arachidonic acid. Their name derives from the prostate gland,
Some prostaglandins stimulate contraction of the smooth muscle of
the uterus during menstruation and labor.
• Steroids are oxidized derivatives of sterols. Steroid hormones move
through the bloodstream (on protein carriers) from their site of
production to target tissues.
Overview of
Metabolism

Figure 1. Outline of the pathways for the catabolism

of dietary carbohydrate, protein, and fat. All the
pathways lead to the production of acetyl-CoA, which is
oxidized in the citric acid cycle, ultimately yielding ATP
in the process of oxidative phosphorylation.
Digestion, Mobilization, and Transport of Fats
Dietary Fats Are Absorbed in the Small Intestine
Mobilization of triacylglycerols stored in adipose tissue.
1. The hormone binds its receptor in the adipocyte
membrane
2. Stimulates adenylyl cyclase, via a G protein, to
produce cAMP. This activates PKA, which
phosphorylates
3. The hormone-sensitive lipase
4. Perilipin molecules on the surface of the lipid
droplet. Phosphorylation of perilipin permits
hormonesensitive lipase access to the surface of the
lipid droplet
5. It hydrolyzes triacylglycerols to free fatty acids.
6. Fatty acids leave the adipocyte, bind serum albumin
in the blood, and are carried in the blood; they are
released from the albumin
7. Enter a myocyte via a specific fatty acid transporter.
8. In the myocyte, fatty acids are oxidized to CO2, and
the energy of oxidation is conserved in ATP, which
fuels muscle contraction and other energy requiring
metabolism in the myocyte.
Figure
Transport and fate of major
lipid substrates and
metabolites. (FFA, free
fatty acids; LPL, lipoprotein
lipase; MG,
monoacylglycerol; TG,
triacylglycerol; VLDL, very
low density lipoprotein.)
FATTY ACID CATABOLISM
Fatty Acids Are Activated and Transported
into Mitochondria

Conversion of a fatty acid to a fatty

acyl–CoA.
Fatty acid activation by formation of
the fatty acyl–CoA derivative occurs in
two steps.
In step 1 , the carboxylate ion
displaces the outer two ( and )
phosphates of ATP to form a fatty
acyl–adenylate
In step 2 , the thiol group of coenzyme
A carries out nucleophilic attack on the
enzyme-bound mixed anhydride,
displacing AMP and forming
the thioester fatty acyl–CoA.
Fatty acid entry into mitochondria via the acyl-
carnitine/ carnitine transporter
Oxidation of Fatty Acids

Four step :

1.Dehydrogenation
2.Hydration
3.Dehydrogenation
4.Thiolisis
Stages of fatty acid oxidation.

Stage 1: A long-chain fatty acid is oxidized to yield acetyl

residues in the form of acetyl- CoA.

Stage 2: The acetyl groups are oxidized to CO2 via the

citric acid cycle.

Stage 3: Electrons derived from the oxidations of stages 1

and 2 pass to O2 via the mitochondrial respiratory chain,
providing the energy for ATP synthesis
Total of ATP

Palmitoyl-CoA + 7CoA + 7FAD + 7NAD + 7H2O

8 acetyl-CoA + 7FADH2 + 7NADH + 7H

8 acetyl-CoA = 8 x 10 ATP = 80 ATP

7 FADH2 = 7 x 1,5 ATP = 10,5 ATP
7 NADH = 7 x 2,5 ATP = 17,5 ATP
= 108 ATP
Activated Fatty Acid = -2 ATP
Total = 106 ATP
Oxidation of a unsaturated fatty acid

Oleic acid as oleoyl-CoA (9), is the example used here.

Oxidation requires an additional enzyme, enoyl-CoA
isomerase, to reposition the double bond, converting the
cis isomer to a trans isomer, a normal intermediate
in oxidation.
Formation of ketone bodies from acetyl-CoA.
• When acetyl-CoA accumulates, thiolase catalyzes the
condensation of two acetyl-CoA molecules to
acetoacetyl-CoA, the parent compound of the three
ketone bodies.
• The reactions of ketone body formation occur in the
matrix of liver mitochondria.
Biosyntesis Of Fatty Acid
Biosyntesis Of Fatty Acid
The acetyl-CoA carboxylase
reaction. Acetyl-CoA carboxylase has
three functional regions: biotin carrier
protein (gray); biotin carboxylase,
which activates CO2 by attaching it to a
nitrogen in the biotin ring in an ATP-
dependent and transcarboxylase,
which transfers activated CO2 (shaded
green) from biotin to acetyl-CoA,
producing malonyl-CoA.
Addition of two carbons to a
growing fatty acyl chain:
a four-step sequence.
Each malonyl group and acetyl
(or longer acyl) group is
activated by a thioester that
links it to fatty acid synthase,
1. Condensation of an activated
acyl group (an acetyl group
from acetyl-CoA is the first acyl
group) and two carbons derived
from malonyl-CoA, with
elimination of CO2 from the
malonyl group, extends the acyl
chain by two carbons.
2. the -keto group is reduced to
an alcohol,
3. elimination of H2O creates a
double bond,
4. the double bond is reduced
to form the corresponding
saturated fatty acyl group.
The triacylglycerol cycle
Biosynthesis of
Triacylglycerols
Biosyntesis Of Phospholipid
In general, the assembly of
phospholipids

1. Synthesis of the backbone molecule

(glycerol or sphingosine)

2. Attachment of fatty acid(s) to the

backbone through an ester or amide
linkage

3. Addition of a hydrophilic head group

to the backbone through a
phosphodiester linkage

4. Alteration or exchange of the head

group to yield the final phospholipid
product.
Origin of the polar head groups of
phospholipids in E. coli.
Biosynthesis of Sphingolipids
Biosynthesis of Cholesterol
1 Synthesis of Mevalonate from 2
Acetate