Lipid' Definition A substance that is relatively insoluble in water, and can be extracted from a cel

1
Todays topic - Lipids membranes (Chapter
8).
Lipid. Definition A substance that is
relatively insoluble in water, and can be
extracted from a cell with a non-polar solvent.
Some lipids Fatty acids.
Triacylglycerols. Phospholipids. Vitamins
A,D,E,K. Sphingolipids. Cholesterol.
2
Fatty acids (FAs).
Fatty acid
Carboxylic acids with chains of varying
lengths. 12 to 24 carbons are common, usually
even numbers. pKa is about 4, so negative charge
at physiological pH.
Fatty acid
3
Some common saturated fatty acids.
(saturated means no double bonds in carbon chain).
Laurate, 12 carbons. Myristate, 14
carbons. Palmitate, 16 carbons. Stearate, 18
carbons. Arachinate, 20 carbons.
palmitate
stearate
4
Some common unsaturated fatty acids.
Oleate (or oleic acid), an unsaturated fatty acid.
Linoleate (or linoleic acid), a polyunsaturated
fatty acid.
5
Unsaturated fatty acids can be either cis or
trans isomer around double bond. Large majority
of naturally occurring fatty acids are cis.
Trans have higher melting point than cis (trans
FAs pack together better, tend to form solids).
6
Triacylglycerols (TAGs).
Fatty acid
(FA)
(TAG)
7
Tristearin (a simple triacylglycerol).
8
A mixed triacylglycerol.
9
Fatty acids (FAs) and triacylglycerols (TAGs)
FAs and TAGs store a lot of energy in a small
volume. Denser energy storage than carbohydrates
(fats can be packed together tightly without
intervening water). Compare 38 kJ/g in fats
versus 16 kJ/g in carbohydrates. Difference is
because fats are more reduced (less oxidized)
than carbohydrates.
10
Fats in a typical human diet.
Animal fat. Example lard (pig fat)
The most abundant fatty acids in lard are
palmitic stearic acid.
palmitic acid
stearic acid
11
Vegetable oil.
Brassica rapum is the source of rapeseed oil.
Traditional plant breeding was used to create
this popular source of vegetable oil. Rapeseed
oil is marketed as Canola oil. The canola oil
name comes from Canada oil.
The most abundant fatty acids in canola oil are
oleic acid (60), linoleic acid (20) and alpha
linolenic acid (10). Saturated fatty acids are
only about 7 of canola oil.
oleic acid
linoleic acid
12
Omega-3 fatty acids
Canola oil contains a lot of omega-3 fatty acid
about 10 of the fatty acids in canola oil are
omega-3.
Omega-3 means the first double bond is on the
3rd carbon from the end of the chain.
alpha linolenic acid
Alpha linolenic acid is very abundant in canola
oil.
13
Essential fatty acids
The human body can make most of the fatty acid
types it needs. But you must have some omega-3
and omega-6 fatty acids in your diet.
alpha linolenic acid is an example of an omega-3
FA
gamma linoleic acid is an example of an omega-6 FA
The omega-3 and omega-6 FAs are precursors for a
number of important molecules. For example,
prostaglandins are hormones that are synthesized
from omega-6 fatty acids.
Prostaglandin E1
14
Notice that canola oil is liquid (unsaturated
fat), and lard is solid (mostly saturated fat).
15
There are many food applications where it is
desirable to have the texture of a solid fat,
with the inexpensiveness of a vegetable oil. For
example, think of Crisco, and the white stuff in
the middle of oreo cookies.
Vegetable oils can be made solid by chemically
hydrogenating some of their double bonds.
Hydrogenated vegetable oil has the perfect
texture for oreo cookie filling.
16
trans fat
cis fat
Hydrogenation results in a mixture of saturated
fatty acids, and fatty acids with some double
bonds, in a mixture of cis and trans
isomers. These latter are called trans
fats. Trans fats also occur in natural fats, but
only in very small amounts. Trans fats have the
unfortunate property of increasing risk for heart
disease. Most likely due to the human lipase
enzymes preference for breaking down cis fats,
and the tendency of trans fats to solidify at
human body temperature.
17
Lipids are the major component of membranes.
Membranes separate cells from their
environment. Also, membranes separate
intercellular regions (such as mitochondria,
vesicles, nucleus).
Lipid bilayer
18
Phospholipids that are commonly found in
membranes.
19
An example of a sphingolipid.
sphingosine
20
Examples of glycosylated sphingolipids.
21
Cholesterol is a lipid that is found in membranes.
22
Lipids in some membrane types.
23
Red squiggles are cholesterol.
24
Lipids in membranes are mobile.
25
Lipids in membranes are mobile.
Above a melting temperature, lipids in membrane
are fluid (liquid-like). Melting temp. depends
on chain length degree of saturation. Double
bonds prevent close packing, lower melting
temperature. Arctic fish have very high
amounts of unsaturated fatty acids, to keep their
membranes fluid.
26
(No Transcript)
27
A membrane-spanning helix contains mostly
hydrophobic amino acids (occurs in membrane
proteins).
28
(No Transcript)
29
Fluid means the membrane interior is
liquid-like (the lipids are mobile). Mosaic
means the membrane is a mosaic of different types
of components (phosphate groups, carboxylic
acids, proteins, sugars).
30
Fuzzy stuff on the surface is the sugar part of
the glycolipids.
31
Type B blood - terminal sugar is galactose. Type
A blood - terminal sugar is N-acetylated
galactose. Type O blood - terminal sugar is
neither of above.
32
Membranes are permeable to small non-polar
uncharged molecules (includes O2 and N2 and
CO2). Impermeable to ions and most other
water-soluble molecules these need specific
transporters to get across the membrane.
33
Ions such as Na and K can NOT pass through
lipid membranes (except through special pores)
34
Types of transport across membranes.
Passive transport - Molecules move down a
concentration gradient (from a region of high
concentration to low concentration).
Active transport - Molecules move across a
membrane against a concentration gradient (from a
region of low concentration to high
concentration). Active transport requires
energy, which is often provided by ATP hydrolysis
to ADP energy.
35
The red blood cell glucose transporter (only lets
glucose through, passive transport).
36
Uniport - specific for one type of
molecule. Symport - transports 2 molecules
together. Antiport - transports 2 molecules in
opposite directions.
37
Active transport requires energy (ATP
hydrolysis). Can work against a
concentration gradient. Example of active
transport Na/K pump (Na conc is
higher outside cells). 3 Na ions bind to
transporter protein inside cell. ATP
phosphorylates protein, causes conformational
change. The 3 Na ions are released outside
cell 2 K ions bound. Triggers
dephosphorylation of protein. Protein goes
back to original state K released inside
cell. This is an antiport two ions moving
in opposite directions through the some
transporter.
A good animation of the Na/K pump
google animation sodium potassium pump
38
Porins - Relatively simple transporters located
in bacterial outer membranes, mitochondria and
chloroplasts. Porin proteins are trimeric, a
group of 3 beta-barrels. Core of barrel has
narrow aqueous channel. Small molecules with MW
less than about 600 can pass through.
OmpF trimer view of one beta-barrel (from text)
The E. coli OmpF protein is a porin. OmpF stands
for outer membrane protein F.
39
Ion channels - Found in neurons and other
eukaryotic proteins, as well as bacteria.
A well-known ion channel is the potassium channel
(bacterial). Allows potassium to pass, but not
sodium.
The core of the potassium ion channel has an
arrangement of backbone carbonyl atoms that has
the correct geometry to coordinate potassium
ions, but not sodium.
40
Membrane potential - Many cells have a charge
imbalance across the membrane, typically excess
negative charge inside the cell, and excess
positive charge outside (due to different Na and
K inside and outside cell). This charge
imbalance results in a voltage across the
membrane. Typical animal cells have a membrane
potential of about 70 mVolts, due to difference
in Na and K inside and outside cells.
41
When an axon of a nerve cell is stimulated, Na
channels in the membrane open, allowing Na to
cross, and altering the membrane potential,
typically from -70 mV to 50 mV, within a
millisecond. This triggers the opening of a
nearby K channel, which returns the potential to
-70 mV, and stimulates other Na channels farther
along the neuron.
This propagating voltage change is called an
action potential. Action potentials propagate
rapidly along an axon (in milliseconds).
42
Axons are wrapped and insulated in a myelin
sheath. This is several layers of membrane
derived from another cell. The myelin sheath is
about 70 lipid, rich in sphingomyelin, and
relatively little protein. The myelin sheath
permits the action potential to propagate faster
more efficiently than it would along an
unwrapped axon. Multiple sclerosis results in a
deterioration of the myelin sheaths.
43
Several vitamins are lipids.
44
Vitamins.
Definition - Organic compound that are required
in small amounts.
Say a few words about the lipid vitamins (the
fat soluble vitamins).
Vitamin A Vitamin D Vitamin E Vitamin K
Lipid vitamins
Water soluble vitamins
B1, B2, B3, B5, B6, B7, B9, B12
(we will discuss water soluble vitamins later in
the course)
45
Vitamin A - Retinol
Retinol (vitamin A)
Sources in diet - Many plants, also meat,
especially liver. Vitamin A is fat soluble. You
can get too much, or too little if absorption is
a problem.
Some uses of vitamin A Vision (11-cis-retinol
bound to rhodopsin detects light in our eyes).
Regulating gene transcription (retinoic acid
receptors on cell nuclei are part of a system for
regulating transcription of mRNAs for a number of
genes).
46
Vitamin D refers to a group of similar
lipid-soluble molecules (major forms are D2 and
D3, also D1, D4, D5).
Vitamin D2 (ergocalciferol)
Vitamin D3 (cholecalciferol)
47
Vitamin D can be obtained in the diet, or derived
from cholesterol in a reaction that requires UV
light.
48
Vitamin D binds to a vitamin D binding protein
(VDP) for transport to target organs. Why is VDP
needed? Vitamin D is not active itself it is
modified to yield biologically active forms, such
as calcitriol. Calcitriol (derived from vitamin
D) is a transcription factor, influencing
expression of proteins involved in calcium
absorption and transport. Deficiency causes bone
loss. Vitamin D is also important for immune
system function.
49
Vitamin D production requires UV light
(sunlight). Sometime after the first humans
migrated north out of Africa about 50,000 years
ago, mutations appeared that reduced melanin
(pigment) production in the skin, permitting
vitamin D production with less sunlight. Disadvan
tages of less melanin production are skin that is
easily damaged by the sun, skin cancer risk, and
loss of folic acid due to UV damage. The
melanin-reducing mutations helped early humans
make vitamin D in northern europe in winter.
50
Human migration.
These groups have mutations resulting in the most
dramatic melanin deficiency.
Thousands of years ago.
Map from wikipedia.
51
In Texas, there is too much sun and plenty of
vitamin D, so I want my melanin back !