Download Lipids (McMurry Ch. 27)

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 & Oils—27.1–27.2)
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+, – COOThese 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
H 2C
HC
H2 C
OH
OH
OH
+
HOOC
R1
HOOC
R2
HOOC
R3
H 2C
C
O
HC
O
C
O
O
H2 C
O
R1
R2
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)
2)
3)
4)
TAG that are solid at room temperature are classified as fats (animal-based)
TAG that are liquid at room temp. are classified as oils (vegetable-based)
In general, the more unsaturated the fatty acids in a TAG, the less solid it is
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 doesn’t 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
Some common antioxidants:
O
+ RH
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-3’s are generally highly unsaturated, so they lower LDLs, raise HDLs
2. Omega-3’s 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
3 CH3(CH2)nCOO- Na+ +
[CH3(CH2)nCOO]3-glycerol
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