Biochemistry Mary K. Campbell PowerPoint by William H. Brown Beloit College Copyright © 1999 by...

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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6-2Copyright (c) 1999 by Harcout Brace & CompanyAll rights reserved

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)


O

A major component of carnauba wax

(the Brazilian wax palm)


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

Biochemistry Mary K. Campbell PowerPoint by William H. Brown Beloit College Copyright © 1999 by...

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