Mary K. Campbell
PowerPoint by
William H. Brown
Beloit College
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6
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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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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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Carbon Atoms/
Double Bonds
12:0
14:0
16:0
18:0
20:0
16:1
18:1
18:2
18:3
20:4
Common
Name lauric acid myristic acid palmitic acid stearic acid arachidic acid palmitoleic acid oleic acid linoleic acid linolenic acid arachidonic acid
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(°C)
-0.5
16
-5
-11
-49
44
58
63
71
77
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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
• 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
CH
R' CO- CH
2
O- CR
O
CH
2
O- CR' '
A triacylglycerol
(a triglyceride)
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Na OH, H
2
O
CH
2
OH
HOCH +
CH
2
OH
1,2,3-Propanetriol
(Glycerol, glycerin)
RCO
2
-
Na
+
R' CO
2
-
Na
+
R' ' CO
2
-
Na
+
Sodium
Soaps
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Soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions
( hard water )
2 CH
3
( CH
2
CO
2
-
Na
+
)
1 4
A sodium soap
(soluble in water as micelles)
+ Ca
2 +
[ CH
3
( CH
2
)
1 4
CO
2
-
]
2
Ca
Calcium salt of a fatty acid
(insoluble in water)
2 +
+ 2 Na
+
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• 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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A phosphatidic acid stearic acid
O
O
O
CH
2
-O- P-O
-
O
-
CH
O CH
2 glycerol
O palmitic acid
• 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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Name and Formula ethanolamine
- OCH
2
CH
2
N H
2 choline
- OCH
2
CH
2
+
N ( CH
3
)
3 serine
- OCH
2
CHCO
2
+
N H
3
-
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Name of Phospholipid phosphatidylethanolamine
(cephalin) phosphatidylcholine
(lecithin) phosphatidylserine
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inositol phosphatidylinositol
OH
-O OH
HO
HO OH glycerol
OH
- OCH
2
CHCH
2
OH phosphatidylglycerol phosphatidylglycerol
OH O O
- OCH
2
CHCH
2
OPOCHOCR
3
O
-
CH
2
OCR
4
O diphosphophaticylglycerol
(cardiolipin)
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A lecithin choline stearic acid palmitic acid
O
O
O P OCH
2
-
CH
2
O
CH
2
+
N( CH
3
)
3
O CH
O
O CH
2 glycerol
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6-13

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• Esters of long-chain fatty acids and alcohols
• from the Old English word weax = honeycomb
O O
CH
3
( CH
2
)
1 4
CO( CH
2
(honeycombs)
)
3 0
CH
3
A major component of beeswax
O
CH
3
( CH
2
)
3 0
CO( CH
2
)
3 3
A major component of
CH carnauba wax
(the Brazilian wax palm)
3
CH
3
( CH
2
)
1 4
CO( CH
2
)
1 5
A major component of
CH spermacetti wax
(head of the sperm whale)
3
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( CH
2
)
1 2
CH
3
HO
N H
2
OH
Sphingosine
HO
( CH
2
)
1 2
CH
3
( CH
2
)
1 2
CH
3
O
HO
N HCR
O
O
-
N HCR
OPOCH
2
O
CH
2
N( CH
+
3
A sphingomyelin
)
3
OH
A ceramide
(an N-acylsphingosine)
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Glycolipid : a compound in which a carbohydrate is bound to an -OH of the lipid
• many glycolipids are derived from ceramides
( CH
2
)
1 2
CH
3 a unit of
 -D-glucopyranose
HO
H
OH
O
N HCR
H
O
HO
HO
O
H a  -glucoside bond
H
OH
H
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Steroids : a group of plant and animal lipids that have this tetracyclic ring structure
A B
C D
• The features common to the ring system of most naturally occurring steroids are illustrated on the next screen
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6
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CH
3
H
CH
3
H
H
H
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HO
H
3
C
H
3
C
H
H H
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Androgens - male sex hormones
• synthesized in the testes
• responsible for the development of male secondary sex characteristics
H
3
C
H
3
C
OH
H
H H
3
C
H
3
C
H
O
H H H H
O HO
Testosterone Androsterone
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Estrogens - female sex hormones
• synthesized in the ovaries
• responsible for the development of female secondary sex characteristics and control of the menstrual cycle
H
3
C
H
3
C
CH
3
C= O
H
H
H
3
C
OH
H
H H H
O
Progesterone
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H
HO
Estradiol
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•
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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• 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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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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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 sideby-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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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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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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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

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Vitamin A, or retinol, occurs only in the animal world
CH
3
CH
3
CH
3
CH
2
OH
CH
3
CH
3
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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CH
3
CH
3
CH
3 site of cleavage H
3
C
H
3
C
CH
CH
3
3
CH
3

Carotene
CH
3
CH
3
CH enzyme-catalyzed cleavage and reduction in the liver
3
CH
3
CH
3
CH
2
OH
CH
3
CH
3
Retinol (Vitamin A)
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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 -NH
2 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
CH
3
CH
3
CH
3
11-12 cis configuration
CH
3
11
12
CH=N-opsin
H
3
C
CH
3
CH
3
CH
3 light
CH
3
11
12
CH
3
CH=N-opsin
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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 D
3
HO
Vitamin D
3
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6
Cholecalciferol
(Vitamin D
3
)
HO
Cholesterol oxidation
HO
HO
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7-Dehydrocholesterol
UV
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OH
Cholecalciferol
Vitamin D
3
)
1, 25-Dihydroxycholecalciferol
OH
HO
O
2 liver
HO
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HO
25-Hydroxycholecalciferol
OH
O
2 kidney
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Vitamin E is a group of compounds of similar structure; the most active is a
-tocopherol
OH
H
3
C CH
3 four isoprene units beginning here and ending at the aromatic ring
H
3
C
O
H
3
C
CH
3
CH
3
CH
3
CH
3
Vitamin E ( a -Tocopherol)
• an antioxidant; traps HOO• and ROO• radicals formed as a result of oxidation by O
2 of unsaturated hydrocarbon chains in membrane phospholipids
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The name of this vitamin comes from the German word Koagulation, signifying its important role in the blood-clotting process isoprene units
Vitamin K
1
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Menadione
(a synthetic vitamin K analog)
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H
CH
2
- CH
CO
2
-
Glutamate side chain of prothrombin
CO
2
CO
2
vit. K
CH
2
- CH
CO
2
-
Carboxylated glutamate side chain of prothrombin
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O
C O
CH
2
- CH Ca
C O
O
Carboxylated glutamate side chain binding calcium ion
Ca
2 +
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Prostaglandins : a family of compounds that have the 20-carbon skeleton of prostanoic acid
9
8
7
6
5
4
3
2
1
CO
2
H
10
11
12
14 16
13 15 17
Prostanoic acid
18
19
20
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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 8
6 5
CO
2
H
11 12 14 15
Arachidonic acid
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• among those synthesized from arachidonic acid are
O
CO
2
H
HO
PGE
2 HO
HO
CO
2
H
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HO
HO
PGF
2 a
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Research on the involvement of PGs in reproductive physiology has produced several clinically useful derivatives
• 15-Methyl-PGF
2a is used as a therapeutic abortifacient extra methyl group at carbon-15
HO
CO
2
H
15
HO
HO CH
3
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15-Methyl-PGF
2 a
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• the PGE
1 analog, misoprostol, is used for prevention of ulceration associated with the use of aspirin-like nonsteroidal antiinflammatory drugs (NSAIDs)
O
CO
2
H
15 16
HO
HO H
PGE
1
O
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HO
CO
2
CH
3
HO CH
3
15
16
Misoprostol
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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
CO
2
H
L-cysteine
Leukotriene C
(its synthesis and release is triggered by allergic reactions)
H S
CH
2
CH
2
CHCO
2
-
NH
2
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• derived from arachidonic acid
• contain a four-membered cyclic ether within a sixmembered ring
• induce platelet aggregation and smooth muscle contraction
H
O
CO
H O
OH
Thromboxane A
2
(a potent vasoconstrictor)
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2
H
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