BiochemistryBiochemistryMary K. CampbellMary K. Campbell
PowerPoint byPowerPoint byWilliam H. BrownWilliam H. BrownBeloit CollegeBeloit College
Copyright © 1999 by Harcourt Brace & CompanyAll rights reserved.Requests for permission to make copies of any part of the work should be mailed to:Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777
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Lipids and Lipids and MembranesMembranes
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LipidsLipids• LipidsLipids: 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 AcidsFatty Acids• Fatty acidFatty 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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Fatty AcidsFatty Acids
20:418:318:218:116:1
20:018:016:014:012:0
Carbon Atoms/Double Bonds
mp(°C)
Common Name
-49-11-516-0.5
7771635844
arachidonic acidlinolenic acidlinoleic acidoleic acidpalmitoleic acid
arachidic acidstearic acidpalmitic acidmyristic acidlauric acid
Saturated
Unsaturated
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Fatty AcidsFatty 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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TriacylglycerolsTriacylglycerols• Triacylglycerol (triglyceride)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)
A triacylglycerol(a triglyceride)
CH2 O-CR
O
O
O
CH2 O-CR''
NaOH, H2O
CH2 OH
CH2 OH 1,2,3-Propanetriol(Glycerol, glycerin)
+
RCO2-Na+
SodiumSoaps
HOCH
R'CO-CH
R'CO2-Na+
R''CO2-Na+
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SoapsSoaps• Soaps form water-insoluble salts when used in
water containing Ca(II), Mg(II), and Fe(III) ions (hard waterhard water)
+
+
A sodium soap(soluble in water as micelles)
Calcium salt of a fatty acid(insoluble in water)
2CH3 (CH2)1 4 CO2- Na+ Ca2 +
[CH3 (CH2)1 4 CO2- ]2Ca2 + 2Na+
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PhosphoacylglycerolsPhosphoacylglycerols• PhosphoacylglycerolsPhosphoacylglycerols (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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PhosphoacylglycerolsPhosphoacylglycerols• A phosphatidic acid
• further esterification with a low-molecular weight alcohol gives a phosphoacylglycerol
• among the most common of these low-molecular-weight alcohols are
CH2
CH
CH2-O-P-O-
O
O
O
O
O
O-
glycerol
palmitic acid
stearic acid
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PhosphoacylglycerolsPhosphoacylglycerols
Name and Formula Name of Phospholipid
ethanolamine
+choline phosphatidylcholine(lecithin)
phosphatidylethanolamine(cephalin)
serine phosphatidylserine
NH3+
-OCH2 CHCO2-
-OCH2 CH2N(CH3)3
-OCH2 CH2NH2
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PhosphoacylglycerolsPhosphoacylglycerolsinositol phosphatidylinositol
HO-O
OHOH
OHHO
-OCH2 CHCH2OH
glycerol
phosphatidylglycerol
OHphosphatidylglycerol
-OCH2 CHCH2OPOCHOCR3
OH
O-
O
CH2OCR4
O
O
diphosphophaticylglycerol(cardiolipin)
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PhosphoacylglycerolsPhosphoacylglycerols• A lecithin
CH2
CH
CH2
O
O
O
O
O P OCH2CH2N(CH3)3
O
O-
+
palmitic acid
stearic acid
glycerol
choline
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WaxesWaxes• Esters of long-chain fatty acids and alcohols
• from the Old English word weax = honeycomb
CH3(CH2)14CO(CH2)30CH3
O
A major component of beeswax(honeycombs)
CH3(CH2)30CO(CH2)33CH3
O
A major component of carnauba wax
(the Brazilian wax palm)
CH3(CH2)14CO(CH2)15CH3
O
A major component ofspermacetti wax
(head of the sperm whale)
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SphingolipidsSphingolipids
OH
(CH2)12CH3
HO
NH2
Sphingosine
OH
(CH2)12CH3
HO
NHCR
A ceramide(an N-acylsphingosine)
OPOCH2CH2N(CH3)3
(CH2)12CH3
HO
NHCR
A sphingomyelin
O
OO
O-
+
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GlycolipidsGlycolipids• GlycolipidGlycolipid: a compound in which a carbohydrate
is bound to an -OH of the lipid• many glycolipids are derived from ceramides
O
(CH2)12CH3
HO
NHCRO
O
H
HO
H
HO
H
HOH
H
OH
a β-glucosidebond
a unit ofβ- -D glucopyranose
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SteroidsSteroids• SteroidsSteroids: a group of plant and animal lipids that
have this tetracyclic ring structure
• The features common to the ring system of most naturally occurring steroids are illustrated on the next screen
A B
C D
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SteroidsSteroids
HCH3
HH
CH3
H
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CholesterolCholesterol
H3C
HO
H3C
H H
H
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AndrogensAndrogens• Androgens - male sex hormones
• synthesized in the testes• responsible for the development of male secondary
sex characteristics
AndrosteroneTestosteroneO
HOH
H
H3C H
H
H3C H3C
H
HH3C
H
O
HO
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EstrogensEstrogens• Estrogens - female sex hormones
• synthesized in the ovaries• responsible for the development of female secondary
sex characteristics and control of the menstrual cycle
Progesterone Estradiol
H3 C
H
HH3 C
H
C=OH
O
CH3
OH
HO
H
H
H
H3 C
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Biological MembranesBiological 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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Biological MembranesBiological 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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Membrane ProteinsMembrane Proteins• FunctionsFunctions: 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 Mosaic ModelFluid Mosaic Model• FluidFluid: there is lateral motion of components in
the membrane; • proteins, for example, “float” in the membrane and can
move along its plane
• MosaicMosaic: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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Membrane TransportMembrane TransportPassive transportPassive transport
• driven by a concentration gradient • simple diffusionsimple diffusion: a molecule or ion moves through an
opening created by a channel protein• facilitated diffusionfacilitated diffusion: molecule or ion is carried across a
membrane by a carrier protein
• Active transport 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 ReceptorsMembrane 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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Lipid-Soluble VitaminsLipid-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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Vitamin AVitamin A• Vitamin A, or retinol, occurs only in the animal
world
• 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 β-carotene followed by reduction gives two molecules of vitamin A
CH3
CH3
CH3
CH3CH3CH2OH
Retinol (Vitamin A)
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Vitamin AVitamin Asite of cleavage
β-Carotene
enzyme-catalyzed cleavage and reduction in the liver
CH3
CH3
CH3
CH3 CH3
CH3 CH3CH3
CH3
H3C
H3C
CH3
CH3
CH3CH3
CH2OH
Retinol (Vitamin A)
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Vitamin AVitamin 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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Vitamin AVitamin A
CH3
CH3
CH3
CH3CH3CH=N-opsin
11
12
CH3
CH3
CH3H3C
CH3
CH=N-opsin
1112
11-12 cis configuration
light
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Vitamin DVitamin 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
Vitamin D3
HO
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Cholecalciferol(Vitamin D3)
CholesterolHO
7-DehydrocholesterolHO
UV
oxidationHO
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CholecalciferolVitamin D3)
HO
HO
25-Hydroxy-cholecalciferol
HO
OH
OH
OH
1, 25-Dihydroxy-cholecalciferol
liver
kidney
O2
O2
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Vitamin EVitamin E• Vitamin E is a group of compounds of similar
structure; the most active is -tocopherol
• an antioxidant; traps HOO• and ROO• radicals formed as a result of oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids
four isoprene units beginning here and ending at the aromatic ring
Vitamin E (- )Tocopherol
H3C
H3C
H3C
CH3
OH
OCH3 CH3
CH3
CH3
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Vitamin KVitamin K• The name of this vitamin comes from the German
word Koagulation, signifying its important role in the blood-clotting process
Vitamin K1
isoprene units
2
O
O
CH3
O
O
CH32
O
O
CH3
O
O
CH3
Menadione(a synthetic
vitamin K analog)
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CH2-CH
CO2-
vit. K
CO2
H
CH2-CH
CO2-
CO2-
Glutamate side chain of prothrombin
Carboxylated glutamateside chain of prothrombin
Carboxylated glutamate side chain binding calcium ion
Ca2+
CH2-CH
C
C
O
O
Ca
O
O
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ProstaglandinsProstaglandins• ProstaglandinsProstaglandins: a family of compounds that have
the 20-carbon skeleton of prostanoic acid
Prostanoic acid
192018
1716
1514
13
78
9
10
1112
65
43
21CO2H
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ProstaglandinsProstaglandins• Prostaglandins are not stored in tissues as such,
but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers• one such polyunsaturated fatty acid is arachidonic
acid
Arachidonic acid1514
89
11 12
6 5CO2H
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ProstaglandinsProstaglandins• among those synthesized from arachidonic acid are
PGF2
HO
CO2 H
HO
CO2 H
HO
HOHO
O
PGE2
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ProstaglandinsProstaglandins• Research on the involvement of PGs in
reproductive physiology has produced several clinically useful derivatives• 15-Methyl-PGF2a is used as a therapeutic abortifacient
15
15-Methyl-PGF2
extra methyl group -15at carbon
CO2 H
HO
HOHO CH3
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ProstaglandinsProstaglandins• the PGE1 analog, misoprostol, is used for prevention of
ulceration associated with the use of aspirin-like nonsteroidal antiinflammatory drugs (NSAIDs)
1615
Misoprostol
15 16
CO2 CH3HO
O
HO
CH3
HO HHO
OCO2 H
PGE1
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LeukotrienesLeukotrienes• Leukotrienes: derived from arachidonic acid
• found in white blood cells (leukocytes)• an important property is constriction of smooth
muscles, especially in the lungs
L-cysteine
Leukotriene C(its synthesis and release is
triggered by allergic reactions)
NH2
H S
HO H
CO2 H
CH2CH2CHCO2-
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ThromboxanesThromboxanes• derived from arachidonic acid• contain a four-membered cyclic ether within a six-
membered ring• induce platelet aggregation and smooth muscle
contraction
(a potent vasoconstrictor)Thromboxane A2
CO2 HO
OH
O
H
H
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EndEndChapter 6Chapter 6