Transcript Lipids

Power Point to Accompany
Principles and Applications of
Inorganic, Organic, and
Biological Chemistry
Denniston, Topping, and Caret
4th ed
Chapter 18
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
18-1
18.1 Lipids
• Lipids- a collection of organic
molecules united by solubility in
nonpolar solvents.
• Varying chemical composition
• Four main groups
18-2
Main Groups
1. Fatty acids
Saturated and unsaturated
2. Glycerides
Contain glycerol (HOCH2CHOHCH2OH)
3. Nonglycerides
Sphingolipids, steroids, waxes
4. Complex lipids
lipoproteins
18-3
Lipid Functions
• As an energy source, lipids provide 9
kcal of energy per gram.
• Triglycerides provide energy storage in
adipocytes.
• Phosphoglycerides, sphingolipids, and
steroids are part of cell membranes.
• Steroid hormones are critical intercell
messengers.
• Lipid soluble vitamins (A, E, D, E)
• Provide shock absorption and
insulation.
18-4
18.2 Fatty Acids
Lauric acid: a typical saturated fatty acid with
12 carbons in the chain (in salt form)
Fatty acid: 12-20 carbons, even # carbons, no
branching, nonpolar carbon chain, polar
COO- group (as anion).
O
2
H3C
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
C
CH2
O
Nonpolar hydrophobic tail
“Polar” hydrophilic head
18-5
Fatty Acids-2
An unsaturated fatty acid has one or more
carbon-carbon double bonds in the chain.
The first double bond is usually at the ninth
carbon. The double bonds are not
conjugated and are usually cis.
O
H
C C CH2 CH2 CH2 C
O
CH
CH2
CH CH2
2 CH2
H
2
CH2
CH2
CH2
CH2
CH3
2
Palmitoleic acid, salt form
Cis double bond results
in a bent chain and lower mp.
18-6
Fatty Acids-3
Stearic 18:0 (# of C and double bonds)
CH3(CH2)16COOH
Palmitoleic 16:1D9 (D9 position of double bond)
CH3(CH2)5CH=CH (CH2)7COOH
Linolenic
18:2D9,12
CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO
Arachidonic 20:4D5,8,11,14
CH3(CH2)3(CH2CH=CH)4(CH2)3 COOH
18-7
Fatty Acid Properties
Mp increases with carbon number.
Mp of saturated acid is higher than an
unsaturated acid of same carbon
number.
cis double bond prevents good
alignment of molecules in unsaturated
fatty acids. Lowers mp relative to
saturated or trans acid.
18-8
Fatty Acid Reactions-1
Esterification
O
O
H+
R C OH+HO R'
R C O R' + H2O
warm
Acid Hydrolysis
O
O
H+
R C O R' + H2O warm R C OH+HO R'
18-9
Fatty Acid Reactions-2
Saponification
O
R C O R' +NaOH
O
R C ONa + HO R'
Hydrogenation of Double Bonds
O
CH3 CH2 4CH CH CH2CH CH CH2 7 C OH
2 H2, Ni
O
CH3 CH2 16 C OH
18-10
Eicosanoids: Prostaglandins, etc.
Arichadonic acid (20 carbons) is the
eichosanoid presursor.
COO
arachadonic acid
Prostaglandins have hormonelike
activity.
In PGF2, PG stands for prostaglandin; F
for a particular group with OH on C-9;
and the 2 indicates two double bonds.
18-11
Prostaglandin Function
•
•
•
•
•
•
•
•
•
Stimulation of smooth muscle
Regulation of steroid biosynthesis
Inhibition of gastric secretion
Inhibition of hormone-sensitive lipases
Inhibition of platelet aggregation
Stimulation of platelet aggregation
Regulation of nerve transmission
Sensitization to pain
Mediation of inflammatory response
18-12
Aspirin and Prostaglandins
Aspirin inhibits prostaglandin synthesis
by acylating cyclooxygenase, an
enzyme necessary for prostaglandin
synthesis.
Acylated enzyme
arachadonic
acid
NH
cyclooxygenase-NH
cyclooxygenase-NH2
COO
O
+
O C CH3
PGH2
O
C CH3
-
COO
OH
18-13
18.3 Glycerides: Triacylglycerols
When all three alcohol groups of glycerol
form esters with fatty acids a neutral
triacylglycerol (triglyceride) is formed.
Triglycerides serve as energy storage in
adipose cells.
O
Glycerol
part
CH2O C R1
O
CH O C R2
O
CH2O C R3
Fatty acid
chains
18-14
Phosphoglycerides
Have hydrophobic and hydrophilic
domains.
Structural components of membranes
Emulsifying agents
Suspended in water they spontaneously
rearrange into ordered structures
Hydrophobic group to center
Hydrophilic group to water
(Basis of membrane structure)
18-15
Phosphoglycerides-2
When the third OH of glycerol is
esterified to a phosphoric acid or a
phosphoric acid ester instead of a
carboxylic acid, a phosphoacylglycerol
results.
O
O Phosphatidic acid
CH2O C R1
CH2O C R1
O
O
CH O C R2
CH O C R2
O
O
CH2O P OR
CH2O P OH
Phosphatidic ester
18-16
O
O
Phosphatidyl esters, egs.
R=
O
+
CH2 CH2 NH3
CH2O C R1 phosphatidylethanolamine
+
O
CH2 CH2 N(CH3)3
CH O C R2 phosphatidylcholine
(lecithin)
O
CH2O P OR
O
Lecithin has a polar head and is amphipathic.
It is the major phospholipid in pulmonary
surfactant and an emulsifying agent.
18-17
18.4 Nonglyceride Lipids: Sphingolipids
These lipids are based on sphingosine,
are found in plants and animals, and
are common in the nervous system.
CH
CH CH2 12 CH3
CH OH
CH NH2
CH2OH
18-18
Sphingolipids-2
CH
CH CH2 12 CH3
CH OH
A
ceramide
O
CH NH C R1 N-acylsphingosine
CH2OH
CH CH CH2 12 CH3
A sphingomyelin
O
Essential to cerebral function
CH NH C R1
and nerve transmission.
O
CH OH
+
CH2O P O CH2CH2N (CH3)3
O
18-19
Glycolipids or Glycosphingolipids
Frequently a glucose or galactose is bound to
the primary alcohol of a ceramide. The
compound is called a cerebroside. These
compounds are found in the cell
membranes of nerve and brain cells.
CH2 CH CH CH CH CH2 12 CH3
O NH OH
CH2OH
CO
O
H
A cerebroside
H
R1
OH H
HO
H
18-20
H OH
Glycolipids-2: Gangliosides
Gangliosides have oligosaccharide
groups with one or more sialic acid (Nacetylnuraminic acid) residues
attached. Names include M, D, T (#
residues) and subscripts for number of
sugars attached to the ceramide.
See the next slide for the structure of a
ganglioside associated with Tay-Sachs
an autosomal recessive disease
resulting in neurological deterioration.
18-21
Gangleoside GM2
CH2OH
HO
O
OH
NH
CO
CH3
O
H
CH3 C N
CH2OH
O O Sph
CH2OH OH
O
O O
OH
O
OH
-
R
OH
O COO
Sph=ceramide
R = CH OH
CH OH
CH2OH
18-22
Sphingolipid Storage Diseases
Disease
Sympt.
Sph. Lip
Enzyme
Tay-Sachs Blindness,
muscle
weakenss
Gaucher’s Liver and
spleen
enlarge, MR
Krabbe’s demyelation,
MR
Ganglioside b-hexoseGM2
aminidaseA
NiemanPick
Sphingomyelin
MR
Glucocerebroside
b-glucosidase
Galactocer- b-galactosebroside
idase
Sphingomyelinase
18-23
Steroids
Steroids are synthesized from the five
carbon isoprene unit and are part of a
diverse collection of lipids called
isoprenoids. They also fit into the
terpene classification.
O O
CH3
CH3
CH2 C CH CH2 CH2 C CH2CH2 O P O P O
O O
isoprene unit isopentenylpyrophosphate
18-24
Steroids-2
Steroid lipids are based on the ring system
shown below. The next slide shows some
examples of steroid sex hormones and of
cholesterol, a lipid very important in human
physiology.
17
12
13
11
16
D
C
1
9
10
14 15
2
8
B
A
3
7
5
6
4
18-25
Steroid Examples
CH3
CH CH2 CH2 CH2 CH(CH3)2
CH3
H
Cholesterol
CH3
OH
H
H
H
HO
CH3
CH3
H
C O
progesterone
CH3
O
CH3
CH3
O
testosterone
18-26
Wax Esters
Waxes are typically esters of fatty acids
and fatty alcohols. They protect the
skin of plants and fur of animal etc.
Examples of waxes include carnuba,
from the leaves of the Brasilian wax
palm, and beeswax.
O
CH3 CH2 24C O CH2 29 CH3
18-27
18.5 Complex Lipids
Lipoproteins
The term is most often used for
molecular complexes found in blood
plasma of humans.
Contain: neutral lipid core of cholesterol
esters and/or TAGs surrounded by a
layer of phospholopid, cholesterol, and
protein.
Classes: chylomycrons, VLDL, LDL, HDL
18-28
Lipoproteins-2
Chylomycrons: very large and very low
density; transport intestineadipose
VLDL: made in liver; transport lipids to
tissues; depleted one to LDLs.
LDL: carry cholesterol to tissues
HDL: made in liver; scavenge excess
cholesterol esters; “good cholesterol”
18-29
Atherosclerosis
Atheromas (plaque) impede blood flow.
Plaque: smooth muscle cells,
macrophages, cell debris
Macrophages fill with LDLs
Coronary artery disease a very common
consequence. High plasma
concentrations of LDLs correlate with
risk.
18-30
Membrane Receptors
The LDL receptor was discovered during
an investigation of familial
hypercholesterolemia.
When a cell needs cholesterol, it
synthesizes the receptor which
migrates to a coated region of the
membrane. The “captured” cholesterol
is absorbed by endocytosis. Failure to
make the receptor is the most common
problem encountered.
18-31
18.6 Membranes
Each type of cell has a unique
membrane composition with varying
percentages of lipids, proteins, and
some carbohydrates.
The currently accepted model of the
membrane is the fluid mosaic model of
a lipid bilayer.
Some examples follow on the next slide.
18-32
Composition of Some Membranes
Human
erythrocyte
Mouse liver
Mitochondrial (inner)
Spinach
lamellar
Protein % Lipid %
49
43
Carb. %
8
46
54
2-4
76
24
1-2
70
30
6
18-33
G Guidotti, Ann Rev Biochem, 41:731, 1972
Membrane Lipids
1. Fluidity
Lateral movement of phospholipids is
rapid. Flip-flop, from one side to
the other is rare.
Increasing percentage of unsaturated
fats leads to more fluidity.
See next slide.
18-34
A fluid membrane model
18-35
Membrane Lipids-2
2. Selective permeability
The hydrophobic nature of the
membrane makes it impenetrable to
the transport of ionic and polar
substances.
Membrane proteins regulate passage
of ionic and polar substances by
binding to the polar compound or by
providing a channel.
18-36
Membrane Lipids-3
3. Self-sealing capacity
A break in the membrane immediately
and spontaneously seals.
4. Asymmetry
Bulkier molecules occur more often in
the inner side of the membrane.
18-37
Membrane Proteins
Most membranes require proteins to carry out
their functions.
Integral proteins are embedded in and/or
extend through the membrane.
Peripheral proteins are bound to membranes
primarily through interactions with integral
proteins.
18-38
Membrane Transport
The cell membranes is responsible for the
controlled passage of molecules and ions
into and out of cells and organelles.
Binding of hormones and other biomolecules.
With passive transport, there is net movement
of solute to a region of lower concentration
(diffusion)
With facilitated diffusion, a membrane protein
(a permease) assists in diffusion. The
process still requires no energy and is
passive.
18-39
Membrane Transport-2
Passive transport (no direct energy
input)
Simple diffusion-molecules move
through a membrane down a
concentration gradient (toward lower
concentration).
Facilitated diffusion-molecules move
through protein channels in membrane.
18-40
Osmosis
Osmosis is the net flow of water through
a semipermeable membrane (ie. Cell
wall) from a region of low solute
concentration to a region of high solute
concentration.
Osmotic pressure is that which must be
applied to prevent flow of water across
the membrane.
18-41
Osmosis, cont.
If a cell has a higher osmotic
concentration than the surrounding
fluid, it’s fluid is said to be hypertonic.
Water flows into the cell and it may
burst or hemolyze.
If a cell has a lower osmotic concentration than the surrounding fluid, it’s
fluid is said to be hypotonic. Water
flows out og the cell and it shrinks or
crenates..
18-42
Membrane Transport-3
Facilitated diffusion
Chemically or voltage-regulated
e. g. acetyl choline binds to a receptor;
Na+ rushes into the cell causing
depolarization which in turn opens a
voltage gated channel for Na+.
Repolarizaton begins when a voltage+
+
gated K channel opens and K leave
the cell.
18-43
Membrane Transport-4
Facilitated diffusion (cont.)
A carrier protein binds to a molecule.
The protein changes conformation and
releases the molecule into the cell.
This process speeds diffusion but
cannot cause a net increase in solute
concentration over diffusion limits.
18-44
Membrane Transport-5
Active transport
Primary-energy provided by ATP
+
+
e. g. the Na -K pump (Next slide)
Secondary-concentration gradients
generated by primary active transport
are used to move substances across
membranes.
e. g. Na+ gradient (Na+-K+ pump) used
to transport glucose in kidney
tubules.
18-45
Sodium-Potassium Pump
Insert Fig 18.21
18-46
Membrane Transport-6
Cystic fibrous is a result of a missing or
defective plasma membrane
glycoprotein called cystic fibrosis
transmembrane conductance regulator
(CFTR) which functions as a chloride
channel in epithelial cells.
In CF, chloride is retained in the cells,
thick mucous forms due to osmotic
uptake of water in the cells. Chronic
pulmonary problems and infections
result.
18-47
The End
Lipids
18-48