Biological Macromolecules

Lipids
MBmedSc. Nguyen Duong Duc Anh

Office: A1.404
Email: [email protected]

BM090IU – Biology for Biomedical Engineering

Learning Outcomes
1. Understand the chemistry of fatty acids and triglycerides and their
functions as energy storage.
2. Understand the chemistry of phospholipids, sphingolipids, and steroids
and their functions as membrane structures.
3. Understand the chemistry of exemplary signaling lipids
Storage Lipids
Fatty Acid
• Carboxylic acids with hydrocarbon
chains between 4 and 36 carbons.
• Almost all natural fatty acids are
unbranched and have even number
of carbons in their backbone.
• Classifications:
❑ Saturated
❑ Monounsaturated
❑ Polyunsaturated
Saturated Fatty Acids
• Saturated = further addition of hydrogen
to the carbon backbone is impossible.
• No double or triple bonds. The backbone
is usually unbranched and adopted an
extended linear conformation.
• Melting point increases and water
solubility decreases with higher number
of carbons.
Unsaturated Fatty Acids
• Hydrocarbon chains contain one or more
C=C double bonds.
• In plants and fish, most double unsaturated
fatty acids are in cis conformation.
• Cis conformations created kinks that
prevent fatty acids from packing tightly and
regularly
→ Easily disrupted so low melting point.
Trans-Fatty Acids
• Naturally occurring in ruminant animal or
products of partial hydrogenation of
vegetable oil.
• Trans Fatty acids adopt an extended
conformation and can pack more
regularly.
• Higher melting point. Tends to be solid at
room temperature.
• Increased risk of cardiovascular disease.
Trans-Fatty Acids
• In some animals (cattle, sheep, goats, etc.), a specialized organ called the
rumen allows bacterial growth that breaks down otherwise indigestible
plant materials.
• Trans-fat is found naturally in ruminant animals and is the result of this
fermentation.
Annotation of Fatty Acids

a:b Δc

Number of Number of Position of

carbons double bonds double bonds

18:2 Δ9,12 (linoleic acid)

Triacylglycerol
• Triacylglycerol (formerly triglycerides) are
esters of glycerol and three fatty acids.
• Hydrophobic and insoluble in water →
form droplets inside cells.
• Function: storage of fatty acids, energy,
and thermal insulation.
Triacylglycerol as Energy Source
• Oxidation of fatty acids into CO2 and H2O
generates energy for cellular activity.

• Each carbon in triglycerides generates

more energy than carbons in glycogen.

• Not hydrated. So relatively lower weight.

• Glycogen: short-term storage. Lipid: long-

term storage
Understanding Checkpoint
1. Draw fatty acids with the following backbones notations. All double
bonds are in cis configurations:
a. 18:3 Δ9,12,15
b. 18:1 Δ9
c. 20:1 Δ11
d. 20:0
Rank the previous four fatty acids in terms of melting points and explain
your reasoning.

2. Lipase is an enzyme that hydrolyze the ester bonds in triacylglycerides. In

an experiment where lipase is added to a sample of cream, how would
you tell if this reaction is happening?
Structural Lipids
of Membranes
Biological Membrane Overview
• Biological membranes are
phospholipid bilayers acting as barriers
to polar and hydrophobic molecules.
• Consisting of two hydrophilic surfaces,
and a hydrophobic core.
• Major components:
1. Glycerophospholipids
2. Galactolipids & Sulpholipids
3. Ether lipids
2. Sphingosines
3. Sterols
Phospholipids
• Phosphatidic acids are esters of glycerol and:
1. Two fatty acids
2. And a phosphate groups
• Amphipathic: one hydrophobic end and one hydrophilic end. Thus, can self-
assemble into a bilayer in aqueous environment.
• Intermediate in the synthesis of other phospholipids and triacylglycerols.
Phospholipids
• Most phospholipids in membranes are derivatives of phosphatidic acids.
• The commonest phospholipid types have choline group covalently linked
to the phosphate group. (also called phosphatidylcholine)
• The two fatty acids chains are often unsaturated.
Phospholipids
Sphingolipids
• Another common form of phospholipids used sphingosine, a long-chained
amino alcohol, as the backbone instead of glycerol.
• Many sphingolipids is present on cell surface and participate in in cell-cell
recognition. The ABO blood antigens are an example of glycated
sphingolipids.
Steroids
• Core structures: 4 fused rings (3 six-
member rings and 1 five-member ring).
• Sterols are a sub-category of steroids,
where C3 has an –OH group.
• Cholesterol is the most common sterols
in animal membranes. Containing a long
alkyl side chains.
→ Amphipathic. Almost planar and rigid
molecules.

How would this molecule be oriented

in a phospholipid membrane?
Cholesterol: Structural Roles
• Rigid ring structures → restrict membrane mobility and disruption at high
temperature.
• Cholesterol acts as a spacer between alkyl chains of phospholipids →
increase mobility within the membrane and prevent crystallization of fatty
acids at low temperature
Self-Assembly of Lipid Aggregates
• Amphipathic molecules in aqueous environment favor self-assembly in
such away that:
• Hydrophobic regions are kept close to each other
• Hydrophilic regions are pointed towards water
• The types of aggregates dependent on the shape of the lipids.

Fatty acids Phospholipids

Monolayer
• Fatty acids or monoglyceride molecules are wedge-shaped (conical)
• The most stable form of packaging is as a one-layer sphere with no
aqueous interior. Called Micelles.

Remember that the tails are hydrophobic (water-fearing)

Bilayers
• Phospholipid molecules are more cylindrical
in shapes.
• Packed with higher stability as a flat bilayer
surface.
• Bilayers fold back to form a hollow sphere
with aqueous cavity
Understanding Checkpoint
Q1. Explain the functions of cholesterol in membrane structure.

Q2. Another function of cholesterol is to transport fatty acids in the form of

cholesteryl ester.
a. Draw a schematic diagram of cholesteryl ester, indication the
location of ester bond.
b. Can cholesteryl ester form monolayer or bilayer aggregates on its
own in aqueous environment.
Signaling and
Cofactor Lipids
Eicosanoids
• eikos- “twenty”. Eicosanoids are lipids with signaling function synthesized
from a 20-carbon fatty acid. E.g. Prostaglandins and Thromboxane
• Variety of functions: inflammation, pain, fever, blood clot, etc.
• NSAIDs (e.g. aspirin, ibuprofen) relieve pain by inhibiting synthesis of
specific eicosanoids.
Steroids
• Many hormones (signaling molecules)
in the body are steroids.

• Good fat solubility so easily diffusing

across cell membranes.

• By definition, hormones need to be

transported in blood plasma. Look at
the structures and discuss their
difference to cholesterol.

Fat-soluble hormones
 Lipid-Soluble Vitamins
• Vitamins: organic molecules required for health* but cannot be sufficiently
or reliably synthesized in the body. Mostly taken through diets.
• Lipid-soluble vitamins include vitamin A, D, E, and K. Excess is stored in fat
tissues.
• Vitamins either serve as precursors for hormones or cofactors.

*This definition is written from a human-centered perspective.

Examples: Vitamin D

UV RADIATION
Revision Questions
Revision Questions
Q1. Compare and contrast glycogen and triglycerides in terms of their energy
storage functions.

Q2. Cis-oleic acid (18:1 Δ9) melts at 13.4oC while its hydrogenated products
stearic acid melts at 69.4oC.
a. Explain the melting point difference.
b. Make a rough prediction of melting point of trans-oleic acid relative
to cis-oleic acid and stearic acid.
Revision Questions
Q3. Peptides hormones bind to receptors on cell
membrane, while steroid hormones bind to
receptors inside the cells. Explain how this
difference occurs.
Q4. What type of aggregates does the following
lipids form in aqueous environment and why
a. Phosphatidic acid
b. Triacylglycerol
c. Arachidonic acid
Arachidonic acid
 THANK YOU!
“There is no such thing as a dumb question.”
Carl Sagan