Lipids (McMurry Ch.

27)

27.1 Waxes, fats & oils

27.2 Soap & detergents

27.3 Phospholipids & sphingolipids

27.4 Prostaglandins, thromboxanes, leukotrienes

27.5 - 27.6 Isoprenoids

Topics related to Part 1:

trans and natural fats, omega-3 fatty acids and inflammation, HDLs, LDLs &
cholesterol, lipid oxidation and antioxidants; COX activity & COX-1 and COX-2
inhibitors

The chemistry of lipids is all about how structure affects function. This
is generally the case with biomolecules (true of carbohydrates, peptides,
proteins)

Since the fats and oils are esters, their chemistry fits in well with the
previous chapters on carboxylic acid derivatives; reactions of these
molecules are similar

Other important lipids include prostaglandins, phospholipids, terpenes and

steroids

We will discuss information that is not covered in the textbook. Take careful
notes in class.

OWL homework* on this chapter is brief, and rather inadequate. Some

supplemental HW problems listed below from the McMurry textbook should help:

Chapter 27: 14, 17, 20, 22, 24, 25, 33, 35, 38, 46
Lipids: Structure, Function & Chemistry

1. Waxes (27.1)
Structure: Esters of long-chain fatty acids and long-chain alcohols
Function: Coatings, protection against environment
Example: Carnauba wax (palm leaves) : CH3(CH2)30-COO-(CH2)33CH3

2. Fatty acids & Triacylglycerols (Fats & Oils27.127.2)

Fatty acid behavior & micelle formation was introduced in Ch. 21
Structure of fats & oils: glycerol backbone esterified with three fatty acids
Function: Fatty acid storage, long-term source of energy, layer of insulation
Structure & composition: see Table 23.1, 23.2, more details to follow

3. Phospholipids & Sphingolipids (Section 27.3)

Structure: Glycerol or sphingosine backbone with phosphoesters, fatty acid
esters, amides and/or sugars attached
Function: Primary component of cell membranes

4. Prostaglandins & other eicosanoids (Section 27.4)

Structure: Derivatives of arachidonic acid, a 20-C fatty acid
Functions: Regulation of physiological processes, inflammatory response

5. Isoprenoids: Terpenoids & steroids (Essential oils, Hormones, Vitamins, etc.)

Structure: Hydrocarbon chain & ring structures composed of isoprene units
Functions: Many! Details in section 27.5 27.6

Physical properties of lipid classes: Behavior of lipids depends on polarity!

Intermolecular forces play a vital role in the function & behavior of lipids.

Hydrophobic = non-polar, comprised mainly of hydrocarbon chains, rings

Hydrophobic structures tend to aggregate together
Hydrophobic interactions = London dispersion forces

Hydrophilic = polar structures, comprised of polar and charged functional groups

such as OH, COOH, CHO, NH2, amides, -NR3+, COO-
These groups are attracted to and are soluble in water through
dipole-dipole forces and hydrogen bonding interactions.

Amphiphilic = Structures which have both nonpolar areas and polar or charged
areas. This will affect how these molecules aggregate together.
Fatty acids: Common long-chain carboxylic acids are shown in Table 27.1
Some key points about fatty acid structure & properties:

1) The number of C in the chain is always even - biosynthesis by condensation

of decarboxylated malonyl esters adds 2 C pieces to growing chain.

2) Saturated fatty acids of 12 - 20 C are common; overall shape = straight

3) Unsaturated fatty acids in nature are always cis (Z) isomers; puts a kink in
the chains & affects 3-D structure (trans-fatty acids only form synthetically)

4) As the number of double bonds increases (polyunsaturated) melting points

decrease
Triacylglycerols (TAG, aka triglycerides)
O

OH HOOC R1 O C R1
H 2C H 2C O
HC OH + HOOC R2 HC O C
R2
O
H2 C HOOC R3 H2 C
OH
O C
R3
Condensation of glycerol with three fatty acids produces a molecule of fat or oil

Some key points about structure and properties of triacylglycerols

1) TAG that are solid at room temperature are classified as fats (animal-based)
2) TAG that are liquid at room temp. are classified as oils (vegetable-based)
3) In general, the more unsaturated the fatty acids in a TAG, the less solid it is
4) Most liquid TAG come from plant sources (olives, corn, safflower)

5) Most solid or primarily saturated fats come from animal sources

6) 3-D structure of fatty acids affects packing which in turn affects melting point

Trans fatty acid is similar in shape to

a saturated fatty acid.

Unsaturated TAG doesnt pack as tightly due to shape

C=C double bonds in nature:
Natural fats contain fatty acids with
double bonds in the cis or Z
configuration.
Chemistry of TAG:

a) Saponification: Base-catalyzed hydrolysis gives glycerol + fatty acid salts

b) Hydrogenation: Rxn with H2/Pt converts unsaturated carbons to saturated

c) Catabolism: TAG undergo acid-catalyzed hydrolysis in stomach (digestion)

Fatty acids break down 2 C at a time to acetyl-CoA which enters citric acid cycle

(Figure 29.3)

d) Lipid peroxidation
and antioxidants

Polyunsaturated fatty acids are easily

oxidized by O2 or oxygen free radicals:

a peroxy radical

an alkyl hydroperoxide
Key point: Fatty acid oxidation contributes to cardiovascular disease.
Oxidation of LDL initiates formation of plaque (solid buildup) in blood vessels and
onset of atherosclerosis and heart disease.

Fatty acids are a major component of:

Lipoproteins, especially LDL (low-density lipoproteins)

Cell membranes; oxidation degrades membranes and makes them less fluid

Oils and fats in food

Oxidation of fatty acids causes rancidity - oxidative cleavage of unsaturated

fatty acids is common, leads to shorter chain aldehydes and acids.

Antioxidants are primarily compounds which react with free radicals (often by
forming a more stable free radical) and remove them from the site before damage
occurs.

Many substituted phenols are antioxidants because they form a stable phenoxyl
radical:

OH + R O + RH

Some common antioxidants:

Dietary fat and the human body

Fats and cholesterol (in the form of fatty acid esters) are carried through the
bloodstream and distributed to and from the tissues and organs by lipoproteins

LDL: Low density lipoproteins carry cholesterol from liver to rest of body
High LDLs tend to deposit more lipid in blood vessels
Lipids are subject to oxidation (see previous page)
High LDL levels raise risk of atherosclerosis and heart disease

HDL: High density lipoproteins carry cholesterol back to the liver

They tend to scavenge lipids left behind
High HDL levels lower cardiovascular disease risk

Effects of dietary fatty acids on serum cholesterol levels:

Mono (MUFA) and polyunsaturated (PUFA):

lower LDL/ raise HDL

Saturated fats:
raise both LDL and HDL

Trans-fats (processed food):

raise LDL
Omega-3-fatty acids (occur mainly in fish, nuts, seeds)

Good for your health!

1. Omega-3s are generally highly unsaturated, so they lower LDLs, raise HDLs

2. Omega-3s are thought to reduce inflammation throughout the body (see

prostaglandins)

Soaps: Fatty acid salts & their physical behavior

Saponification = base-catalyzed formation of carboxylate salts from fats & oils

NaOH
[CH3(CH2)nCOO]3-glycerol 3 CH3(CH2)nCOO- Na+ +
glycerol

Key behavior: Micelle formation (see Ch. 21 notes)

Charged "head" interacts with water while nonpolar "tail" is repelled by

water.

Tails interact with each other through London dispersion forces

("hydrophobic" interaction)
The resulting spherical formation is called a "micelle"

How soap works:

Since most dirt is oil-based, it is attracted to the center of the micelle and the soap
micelles therefore break up dirt particles (but remain soluble due to charged outer
layer)
Phospholipids, sphingolipids and the structure of cell membranes

Their major role is as a barrier between cells and their environment;

separating the cytoplasm and cellular structures from the extracellular fluid
and each other.

Both are classes of amphiphilic molecules, consisting of a charged or polar

head and nonpolar hydrocarbon tails

A typical phospholipid (or phosphoacylglycerol) has a glycerol backbone

with two fatty acid chains and a phosphate ester ending in a charged group
(usually an amine)

Lecithins (phosphatidylcholines) are one of the major components of cell

membranes: Fatty acid structure varies; in egg lecithin, R1 = palmityl R2 = oleoyl

Cephalins (phosphatidylethanolamine) & phosphatidylserine differ in amine

structure

Hydrolysis of a phospholipid produces:

glycerol
two fatty acids
phosphate
an amino alcohol

Sphingolipids differ from other phospholipids by having a sphingosine backbone

Phospholipid Bilayer of cell membrane

Phospholipids naturally arrange themselves in two layers with their hydrophobic

tails pointing inward and their charged ends facing aqueous environment.

Fatty acid ester composition varies; the more unsaturated the groups, the more
fluid and flexible the cell membrane.

Other components of cell membranes:

Cholesterol a steroid member of the terpenoid class of lipids which lends

rigidity to the animal cell membrane

Proteins Various proteins in the membrane function to facilitate transport

across the membrane (integral) or act as receptors for signaling molecules
(peripheral)

Carbohydrates Found on the surface of membranes as parts of

glycoproteins.
Some carbohydrate structures also function as receptors.
Sphingolipids

Occurrence: Sphingolipids are found mainly in nerve and brain cell membranes.
Sphingomyelins make up the myelin sheath surrounding nerves
Cerebrosides (glycolipids) are found in brain tissue
Several human genetic diseases result from faulty metabolism or abnormal
accumulation of sphingolipids in the body:

o Tay-Sachs disease Accumulation of glycolipids in the brain due to lack of

an enzyme (hexosaminidase A) required to metabolize glycolipids results in
severe brain damage.

o Niemann-Pick disease Similarly, lack of an enzyme required to metabolize

sphingomyelin (sphingomyelinase) results in overaccumulation in cells,
severe neurological damage & malfunction of liver and spleen.

o Multiple Sclerosis Breakdown of the myelin sheath due to attack by cells of

the immune system results in slowing of nerve impulses, eventual paralysis.

A sphingolipid structure:
Normally, sphingolipids are metabolized to
their components: sphingosine, fatty
acids, sugars, phosphocholine, etc.

Sphingolipids exhibit bilayer-formation like

phospholipids; overall amphiphilic
behavior

Predict the products of base-catalyzed hydrolysis of this phospholipid:

Prostaglandins and other eicosanoids: Biosynthesis and Functions

Linoleic acid arachidonic acid

Arachidonic acid is converted through a series of enzymatic and free radical
rxns to prostaglandins (Fig. 27.5).
Prostaglandins and related compounds regulate a wealth of physiological
processes

1) Prostaglandins structural features

Precursors:

Biosynthesis: The enzyme endoperoxide synthase (consisting of

cyclooxygenase and hydroperoxidase) converts arachidonic acid to PGH2, the
precursor of all prostaglandins
Functions and physiological effects: Regulation of blood pressure and
reproductive functions; induce inflammation, fever and pain; inhibit platelet
aggregation
Prostaglandins, COX-1 and 2, and Inflammation

Most non-steroidal antiinflammatory drugs (NSAIDS) like aspirin and ibuprofen

work by blocking the action of cyclooxygenase, thereby inhibiting prostaglandin
production
2) Prostacyclin Also made from PGH2
but contains a fused bicyclic structure

Functions:
Opposite of thromboxanes

3) Thromboxanes Also produced from PGH2

but contain a 6-membered oxane ring

Functions: Platelet aggregation, clotting, constriction of blood vessels

4) Leukotrienes Synthesized directly from arachidonic acid; 3 conjugated C=C

bonds but no ring structure

Effects: Smooth muscle contraction, allergic response, lung constriction, swelling