Transcript 06 Lipids

Biochemistry
Mary K. Campbell
PowerPoint by
William H. Brown
Beloit College
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6
Lipids and
Membranes
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6-2
6 Lipids
• Lipids: a heterogeneous class of naturally
occurring organic compounds classified together
on the basis of common solubility properties
• they are insoluble in water, but soluble in aprotic
organic solvents, including diethyl ether, chloroform,
methylene chloride, and acetone
• Lipids include
• triacylglycerols, phosphodiacylglycerols,
sphingolipids, glycolipids, lipid-soluble vitamins, and
prostaglandins
• cholesterol, steroid hormones, and bile acids
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6-3
6 Fatty Acids
• Fatty acid: a long, unbranched chain carboxylic
acid, most commonly of 12 - 20 carbons, derived
from hydrolysis of animal fats, vegetable oils, or
phosphodiacylglycerols of biological membranes
• In the shorthand notation for fatty acids
• the number of carbons and the number of double
bonds in the chain are shown by two numbers,
separated by a colon
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6-4
6 Fatty Acids
Unsaturated
Saturated
Car bon A toms/
Double Bonds
12:0
14:0
16:0
18:0
20:0
16:1
18:1
18:2
18:3
20:4
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Comm on
Name
laur ic acid
myr istic acid
palm itic acid
stearic acid
arachidic acid
palm itoleic acid
oleic acid
linoleic acid
linolenic acid
arachidonic acid
mp
(°C)
44
58
63
71
77
-0.5
16
-5
-11
-49
6-5
6 Fatty Acids
• Among the fatty acids most abundant in plants
and animals
• nearly all have an even number of carbon atoms, most
between 12 and 20, in an unbranched chain
• the three most abundant are palmitic (16:0), stearic
acid (18:0), and oleic acid (18:1)
• in most unsaturated fatty acids, the cis isomer
predominates; the trans isomer is rare
• unsaturated fatty acids have lower melting points than
their saturated counterparts; the greater the degree of
unsaturation, the lower the melting point
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6-6
6 Triacylglycerols
• Triacylglycerol (triglyceride): an ester of glycerol
with three fatty acids
• natural soaps are prepared by boiling triglycerides
(animal fats or vegetable oils) with NaOH, in a reaction
called saponification (Latin, sapo, soap)
O
O
CH2 O- CR
R'CO- CH
Na OH, H2 O
O
CH2 O- CR''
A tr iacylglycerol
(a tr iglycer ide)
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RCO2 - Na +
CH2 OH
HOCH
+
R'CO2 - Na +
CH2 OH
R''CO2 - Na +
1,2,3-Pr opanetriol
Sodium
(Glycerol, glycer in)
Soaps 6-7
6 Soaps
• Soaps form water-insoluble salts when used in
water containing Ca(II), Mg(II), and Fe(III) ions
(hard water)
2 CH3 ( CH2 ) 1 4 CO2
-
Na
+ +
Ca
2+
A sodium soap
(soluble in water as micelles)
-
2+
+ 2 Na
[ CH3 ( CH2 ) 1 4 CO2 ] 2 Ca
Calcium salt of a fatty acid
(insoluble in water)
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+
6-8
6 Phosphoacylglycerols
• Phosphoacylglycerols (phosphoglycerides) are
the second most abundant group of naturally
occurring lipids
• found almost exclusively in plant and animal
membranes, which typically consist of 40% -50%
phosphoacylglycerols and 50% - 60% proteins
• the most abundant phosphoacylglycerols are derived
from phosphatidic acid, a molecule in which glycerol is
esterified with two molecules of fatty acid and one of
phosphoric acid
• the three most abundant fatty acids in phosphatidic
acids are palmitic acid (16:0), stearic acid (18:0), and
oleic acid (18:1)
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6-9
6 Phosphoacylglycerols
• A phosphatidic acid
stearic acid
O
CH2 -O- P-O O
OO CH
O CH2
palm itic acid
O
glycerol
• further esterification with a low-molecular weight
alcohol gives a phosphoacylglycerol
• among the most common of these low-molecularweight alcohols are
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6-10
6 Phosphoacylglycerols
Name and For mula
Name of Phospholipid
ethanolamine
- OCH 2 CH 2 N H 2
phosphatidylethanolam ine
(cephalin)
choline
phosphatidylcholine
(lecithin)
ser ine
- OCH 2 CHCO2
phosphatidylserine
+
- OCH 2 CH 2 N ( CH 3 ) 3
N H3
+
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6-11
6 Phosphoacylglycerols
inositol
-O
HO
glycerol
OH
HO
phosphatidylinositol
OH
OH
phosphatidylglycer ol
OH
- OCH2 CHCH2 OH
phosphatidylglycer ol
diphosphophaticylglycer ol
OH
O
O
(car diolipin)
- OCH2 CHCH2 OPOCHOCR3
O - CH2 OCR4
O
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6-12
6 Phosphoacylglycerols
• A lecithin
stear ic acid
choline
O
O
+
O P OCH2 CH2 N( CH 3 ) 3
O
CH
2
O CH
O CH2
palm itic acid
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glycerol
O
6-13
6 Waxes
• Esters of long-chain fatty acids and alcohols
• from the Old English word weax = honeycomb
O
O
CH3 ( CH 2 ) 1 4 CO( CH2 ) 3 0 CH3 CH3 ( CH2 ) 3 0 CO( CH2 ) 3 3 CH3
A major component of beeswax
A major component of
(honeycom bs)
car nauba wax
(the Br azilian wax palm)
O
CH 3 ( CH2 ) 1 4 CO( CH2 ) 1 5 CH3
A major component of
sper macetti wax
(head of the sper m whale)
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6-14
6 Sphingolipids
( CH2 ) 1 2 CH3
( CH2 ) 1 2 CH3
O
HO
HO
( CH2 ) 1 2 CH3
N H2
OH
HO
Sphingosine
O
N HCR
N HCR
OOPOCH 2 CH 2 N( CH3 ) 3
+
O
A sphingom yelin
OH
A cer amide
(an N-acylsphingosine)
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6-15
6 Glycolipids
• Glycolipid: a compound in which a carbohydrate
is bound to an -OH of the lipid
• many glycolipids are derived from ceramides
( CH2 ) 1 2 CH3
a unit of
-D-glucopyranose
HO
O
N HCR
H OH
HO
HO
HO
O
H
H
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OH
H
a -glucoside
bond
6-16
6 Steroids
• Steroids: a group of plant and animal lipids that
have this tetracyclic ring structure
C
A
D
B
• The features common to the ring system of most
naturally occurring steroids are illustrated on the
next screen
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6-17
6 Steroids
CH3
H
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H
CH3
H
H
6-18
6 Cholesterol
H3 C
H3 C
H
H
H
HO
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6-19
6 Androgens
• Androgens - male sex hormones
• synthesized in the testes
• responsible for the development of male secondary
sex characteristics
H3 C
H3 C
OH
H
H
H
H3 C
H3 C
H
O
O
H
H
H
HO
Testosterone
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Andr oster one
6-20
6 Estrogens
• Estrogens - female sex hormones
• synthesized in the ovaries
• responsible for the development of female secondary
sex characteristics and control of the menstrual cycle
CH3
H3 C
H3 C C= O
H
H3 C OH
H
H
H
H
H
O
H
HO
Pr ogester one
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Estr adiol
6-21
6 Biological Membranes
• In aqueous solution, phosphoglycerides
spontaneously form into a lipid bilayer, with a
back-to-back arrangement of lipid monolayers
(Figure 6.8)
• polar head are in contact with the aqueous
environment
• nonpolar tails are buried within the bilayer
• the major force driving the formation of lipid
bilayers is hydrophobic interaction
• the arrangement of hydrocarbon tails in the interior
can be rigid (if rich in saturated fatty acids) or fluid
(if rich in unsaturated fatty acids)
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6-22
6 Biological Membranes
• the presence of cholesterol increases rigidity
• with heat, membranes become more disordered; the
transition temperature is higher for more rigid
membranes; it is lower for less rigid membranes
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6-23
6 Membrane Proteins
• Functions: transport substances across
membranes, receptor sites, and sites of enzyme
catalysis
• Peripheral proteins
• bound by electrostatic interactions
• can be removed by raising the ionic strength
• Integral proteins
• bound tightly to the interior of the membrane
• removed by treatment with detergents or
ultrasonification
• removal generally denatures them
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6-24
6 Fluid Mosaic Model
• Fluid: there is lateral motion of components in
the membrane;
• proteins, for example, “float” in the membrane and can
move along its plane
• Mosaic:components in the membrane exist side-
by-side as separate entities
• the basic structure is that of a lipid bilayer with
proteins, glycolipids, and steroids such as cholesterol
embedded in it
• no complexes, as for example, lipid-protein complexes,
are formed
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6-25
6 Membrane Transport
Passive transport
• driven by a concentration gradient
• simple diffusion: a molecule or ion moves through an
opening created by a channel protein
• facilitated diffusion: molecule or ion is carried across a
membrane by a carrier protein
• Active transport
• a molecule or ion is moved against a concentration
gradient
• see the Na+/K+ ion pump (Figs 6.19 - 6.20)
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6-26
6 Membrane Receptors
• Membrane receptors
• generally oligomeric proteins
• binding of a biologically active substance to a receptor
initiates an action within the cell
• see the low-density-lipoprotein (LDL) receptor (Fig.
6.21)
• see the Neuromuscular Junction (Figs 6.22-6.24)
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6-27
6 Lipid-Soluble Vitamins
• Vitamins are divided into two broad classes on
the basis of their solubility
• those that are lipid-soluble (and hence classified as
lipids)
• those that are water-soluble
• The lipid-soluble vitamins include A, D, E, and K
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6-28
6 Vitamin A
• Vitamin A, or retinol, occurs only in the animal
world
CH3
CH3
CH3
CH2 OH
CH3
CH3
Retinol (Vitamin A)
• Vitamin A is found in the plant world in the form of a
provitamin in a group of pigments called carotenes
(tetraterpenes)
• enzyme-catalyzed cleavage of -carotene followed by
reduction gives two molecules of vitamin A
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6-29
6 Vitamin A
CH3
CH3
site of
cleavage
CH3
H3 C
CH3
- Car otene
CH3
H3 C
CH3
CH3
CH3
enzym e-catalyzed cleavage
and r eduction in the liver
CH3
CH3
CH3
CH2 OH
CH3
CH3
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Retinol (Vitam in A)
6-30
6 Vitamin A
• The best understood role of Vitamin A is its
participation in the visual cycle in rod cells
• the active molecule is retinal (vitamin A aldehyde),
which forms an imine with an -NH2 group of the protein
opsin to form the visual pigment called rhodopsin
• the primary chemical event of vision in rod cells is
absorption of light by rhodopsin followed by
isomerization of the 11-cis double bond to the 11-trans
configuration
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6-31
6 Vitamin A
CH3
CH 3
11-12 cis configuration
11
12
CH3
CH3
CH=N-ops in
H3 C
light
CH3
CH3
CH3
CH3
11
CH=N-ops in
12
CH3
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6-32
6 Vitamin D
• A group of structurally related compounds that
play a role in the regulation of calcium and
phosphorus metabolism
• the most abundant form in the circulatory system is
vitamin D3
HO
Vitamin D3
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6-33
6
HO
Cholecalciferol
(Vitamin D
3)
Cholester ol
oxidation
HO
UV
7-Dehydr ocholester ol
HO
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6-34
6
OH
Cholecalciferol
Vitamin D
3)
HO
1, 25-Dihydr oxycholecalcifer ol
OH
liver
O2
OH
HO
25-Hydr oxycholecalcifer ol
kidney
O2
HO
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6-35
6 Vitamin E
• Vitamin E is a group of compounds of similar
structure; the most active is a-tocopherol
OH
H3 C
CH3
H3 C
O
H3 C
four isopr ene units beginning
here and ending at the ar omatic r ing
CH3
CH3
Vitamin E a-Tocopher
(
ol)
CH3
CH3
• an antioxidant; traps HOO• and ROO• radicals formed
as a result of oxidation by O2 of unsaturated
hydrocarbon chains in membrane phospholipids
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6-36
6 Vitamin K
• The name of this vitamin comes from the German
word Koagulation, signifying its important role in
the blood-clotting process
isopr ene units
O
CH33
O
Vitamin K
1
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2
O
CH33
Menadione
O
(a synthetic
vitamin K analog)
6-37
O
C
6
H
O
CH2 - CH
CH2 - CH
CO2 -
C O
O
Car boxylated glutam ate
side chain binding
calcium ion
Glutamate side
chain of pr othr om bin
CO2
CO2 -
vit. K
Ca
Ca 2 +
CH2 - CH
CO2 Car boxylated glutam ate
side chain of pr othr ombin
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6-38
6 Prostaglandins
• Prostaglandins: a family of compounds that have
the 20-carbon skeleton of prostanoic acid
7
9
5
1
3
8
6
4
2
12
14
16
18
CO2 H
10
11
13
15
17
19
20
Pr ostanoic acid
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6-39
6 Prostaglandins
• Prostaglandins are not stored in tissues as such,
but are synthesized from membrane-bound 20carbon polyunsaturated fatty acids in response
to specific physiological triggers
• one such polyunsaturated fatty acid is arachidonic acid
9
11
8
12
6
14
5
CO2 H
15
Ar achidonic acid
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6-40
6 Prostaglandins
• among those synthesized from arachidonic acid are
O
CO2 H
HO
HO
PGE2
HO
CO2 H
HO
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HO
PGF2 a
6-41
6 Prostaglandins
• Research on the involvement of PGs in
reproductive physiology has produced several
clinically useful derivatives
• 15-Methyl-PGF2a is used as a therapeutic abortifacient
extr a methyl gr oup
at car bon-15
HO
CO2 H
15
HO
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HO CH3
15-Methyl-PGF2 a
6-42
6 Prostaglandins
• the PGE1 analog, misoprostol, is used for prevention of
ulceration associated with the use of aspirin-like
nonsteroidal antiinflammatory drugs (NSAIDs)
O
CO2 H
15 16
HO
PGE1
HO H
O
CO2 CH3
HO
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HO
15
CH3
16
Misopr ostol
6-43
6 Leukotrienes
• Leukotrienes: derived from arachidonic acid
• found in white blood cells (leukocytes)
• an important property is constriction of smooth
muscles, especially in the lungs
HO H
CO2 H
H S
L-cysteine CH 2 CH 2 CHCO2 Leukotr iene C
NH 2
(its synthesis and release is
trigger ed by aller gic reactions)
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6-44
6 Thromboxanes
• derived from arachidonic acid
• contain a four-membered cyclic ether within a sixmembered ring
• induce platelet aggregation and smooth muscle
contraction
H
O
H
CO2 H
O
OH
Thr om boxane A
2
(a potent vasoconstr ictor)
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6-45
6
End
Chapter 6
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6-46