Lec 4 Lipids

7/30/2019 Lec 4 Lipids

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Introduction Definition: water insoluble compounds

Most lipids are fatty acids or ester of fatty acid They are soluble in non-polar solvents such as petroleum

ether, benzene, chloroform Functions

Energy storage Structure of cell membranes Thermal blanket and cushion

Precursors of hormones (steroids and prostaglandins) Types:

Fatty acids Neutral lipids Phospholipids and other lipids


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Fatty acids Carboxylic acid derivatives of long chain hydrocarbons

Nomenclature (somewhat confusing)

Stearate stearic acid C18:0

n-octadecanoic acid

General structure:

(CH2)nCH3 COOH

n is almost always even

n = 0 : CH3COOH n = 1 : propionic aci


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Fatty acids Common fatty acids

n = 4 butyric acid (butanoic acid)

n = 6 caproic acid (hexanoic acid)n = 8 caprylic acid (octanoic acid)

n = 10 capric acid (decanoic acid)


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Fatty acids common FAs:

n = 12: lauric acid (n-dodecanoic acid; C12:0)n = 14: myristic acid (n-tetradecanoic acid; C

14:0)

n = 16: palmitic acid (n-hexadecanoic acid; C16:0)

n = 18; stearic acid (n-octadecanoic acid; C18:0)

n = 20; arachidic (eicosanoic acid; C20:0)

n= 22; behenic acid

n = 24; lignoceric acid

n = 26; cerotic acid


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Less common fatty acids

iso isobutyric acid

anteiso

odd carbon fatty acid propionic acid hydroxy fatty acids ricinoleic acid,

dihydroxystearic acid, cerebronic acid

cyclic fatty acids hydnocarpic, chaulmoogricacid

R

H3C

H3C H3C

R

CH3

(CH2)12-CO2H (CH2)10-CO2H

chaulmoogric acid hydnocarpic acid


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H3C

CH3 CH3 CH3 CH3

COOH

PHYTANIC ACID

A plant derived fatty acid with 16 carbons and branches at C 3, C7, C11 and

C15. Present in dairy products and ruminant fats.

A peroxisome responsible for the metabolism of phytanic acid is defective

in some individuals. This leads to a disease called Refsums disease

Refsums disease is characterized by peripheral polyneuropathy, cerebellar

ataxia and retinitis pigmentosa


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(CH2)10H3C C C (CH2)4 COOH

TARIRIC ACID

CHH2C (CH2)4 C C C C (CH2)7 COOH

ERYTHROGENIC ACID

Less common fatty acids

These are alkyne fatty acids


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Fatty acids Fatty acids can be classified either as:

saturated or unsaturated

according to chain length: short chain FA: 2-4 carbon atoms

medium chain FA: 6 10 carbon atoms

long chain FA: 12 26 carbon atoms

essential fatty acids vs those that can be biosynthesized in the

body: linoleic and linolenic are two examples of essential fatty acid


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Unsaturated fatty acids Monoenoic acid (monounsaturated)

H3C

HOOC

Double bond is alwayscis in natural fatty acids.

This lowers the melting

point due to kink in

the chain


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Unsaturated fatty acids Dienoic acid: linoleic acid

(CH2)4CH3 CH=CH CH2 CH=CH (CH2)7 COOH

cis

linoleic acid


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Unsaturated fatty acidsVarious conventions are in use for indicating the

number and position of the double bond(s)

HC CH(CH2)7COOH(CH2)7H3C

1918

10

18:1,9 or9

18:1

H3C CH2CH 2CH2CH2CH2CH2CH2CH CH( CH2)7COOH

191017n

2 3 4 5 6 7 8 9 10 18

9, C18:1 or n-9, 18:1


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Unsaturated fatty acids Polyenoic acid (polyunsaturated)

COOH

CH3


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Unsaturated fatty acids Monoenoic acids (one double bond):

16:1, 9 7: palmitoleic acid (cis-9-hexadecenoic acid

18:1, 9 9: oleic acid (cis-9-octadecenoic acid)

18:1, 9 9: elaidic acid (trans-9-octadecenoic acid)

22:1, 13 9: erucic acid (cis-13-docosenoic acid)

24:1, 15 9: nervonic acid (cis-15-tetracosenoic acid)


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Unsaturated fatty acids Trienoic acids (3 double bonds)

18:3;6,9,12 6 : g-linolenic acid (all cis-6,9,12-octadecatrienoicacid)

18:3; 9,12,15 3 : a-linolenic acid (all-cis-9,12,15-octadecatrienoic acid)

Tetraenoic acids (4 double bonds) 20:4; 5,8,11,14 6: arachidonic acid (all-cis-5,8,11,14-

eicosatetraenoic acid)


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Unsaturated fatty acids

Pentaenoic acid (5 double bonds) 20:5; 5,8,11,14,17 3: timnodonic acid or EPA

(all-cis-5,8,11,14,17-eicosapentaenoic acid)*

Hexaenoic acid (6 double bonds) 22:6; 4,7,10,13,16,19 3: cervonic acid or DHA

(all-cis-4,7,10,13,16,19-docosahexaenoic acid)*

Both FAs are found in cold water fish oils


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Typical fish oil supplements


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Properties of fats and oils fats are solids or semi solids

oils are liquids

melting points and boiling points are not usuallysharp (most fats/oils are mixtures)

when shaken with water, oils tend to emulsify

pure fats and oils are colorless and odorless (color

and odor is always a result of contaminants) i.e.butter (bacteria give flavor, carotene gives color)


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Examples of oils Olive oil from Oleo europa (olive tree)

Corn oil fromZea mays

Peanut oil fromArachis hypogaea Cottonseed oil from Gossypium

Sesame oil from Sesamum indicum

Linseed oil from Linum usitatissimum

Sunflower seed oil from Helianthus annuus Rapeseed oil from Brassica rapa

Coconut oil from Cocos nucifera


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Non-drying, semi-drying and drying oils based on the ease of autoxidation and

polymerization of oils (important in paints andvarnishes)

the more unsaturation in the oil, the more likelythe drying process Non-drying oils:

Castor, olive, peanut, rapeseed oils

Semi-drying oils Corn, sesame, cottonseed oils

Drying oils Soybean, sunflower, hemp, linseed, tung, oiticica oils


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Fatty acid reactions salt formation

ester formation

lipid peroxidation

RCO2H RCO2-Na+

NaOH(a soap)

R'OH + RCO2H RCO2R'-H20

R

R'

H H

R R'

OOH

O2

non-enzymatic

very reactive


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Soaps

Process of formation is known as saponification Types of soaps:

Sodium soap ordinary hard soap

Potassium soap soft soap (shaving soaps are potassium

soaps of coconut and palm oils) Castile soap sodium soap of olive oil

Green soap mixture of sodium and potassium linseed oil

Transparent soap contains sucrose

Floating soap contains air

Calcium and magnesium soaps are very poorly water soluble(hard water contains calcium and magnesium salts theseinsolubilize soaps)


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Lipid peroxidation a non-enzymatic reaction catalyzed by oxygen

may occur in tissues or in foods (spoilage) the hydroperoxide formed is very reactive and leads to

the formation of free radicals which oxidize proteinand/or DNA (causes aging and cancer)

principle is also used in drying oils (linseed, tung,walnut) to form hard films


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Hydrogenated fats hydrogenation leads to either saturated fats and or

trans fatty acids

the purpose of hydrogenation is to make the oil/fatmore stable to oxygen and temperature variation(increase shelf life)

example of hydrogenated fats: Crisco, margarine


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Neutral lipids Glycerides (fats and oils) ;glycerides

Glycerol

Ester of glycerol - mono glycerides, diglycerides andtriglycerides

Waxes simple esters of long chain alcohols

CH2OH

CH2OH

OHH OH

OH

OH

glycerol is a prochiral molecule


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GLYCERIDES

O

OH

OH

R

O

O

OH

O

R

O

R

O

O

O

R

O

R

O

OR

O

MONOGLYCERIDE DIGLYCERIDE TRIGLYCERIDE

Function: storage of energy in compact form and cushioning


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WAXES

simple esters of fatty acids (usually saturated with longchain monohydric alcohols)

H3C (CH 2)14 C

O

O CH 2 (CH 2)28-CH 3

long chain alcohol

fatty acid

Beeswaxalso includes some free alcohol and fatty acids

Spermaceticontains cetyl palmitate (from whale oil)useful for

Pharmaceuticals (creams/ointments; tableting and granulation)

Carnauba waxfrom a palm tree from brazila hard wax used on

cars and boats


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Bees wax

Spermaceti source

Carnauba wax source


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Waxes

(CH2)14H3C CH2-OH cetyl alcohol

(CH2)24H3C CH2-OH hexacosanol

(CH2)28H3C CH2-OH triacontanol (myricyl alcoh

Examples of long chain monohydric alcohols found in waxes


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Phospholipids the major components of cell membranes

phosphoglycerides

O R

O R'

O

P

O

O

O

O-

X

Ofatty acids (hydrophobic tail)

glycerol

phosphate

Phospholipids are generally composed of FAs, a nitrogenous base, phosphoric

acid and either glycerol, inositol or sphingosine


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O R

O R'

O

P

O

O

O

O-

X

Ofatty acids (hydrophobic tail)

glycerol

phosphate

X = H (phosphatidic acid) - precursor to other phospholipids

X = CH2-CH2-N+(CH3)3 phosphatidyl choline

X = CH2-CH(COO-)NH3

+phosphatidyl serine

X = CH2-CH2-NH3+

phosphatidyl ethanolamine


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Phosphatidyl inositol

Commonly utilized in cellular signaling


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Sphingolipids

OH

NH2

OH

NH2

OH

HO Rlong chain hydrocarbon

attach fatty acid here

attach polar head group here

sphingosine

Based on sphingosine instead of glycerol


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Sphingomyelin (a ceramide)

NH

O

HO R

PO

O-

O

N(CH3)+

R'

O

usually palmitic acid

phosphatidyl choline (also can be ethanolami

It is a ubiquitous component of animal cell membranes, where it is by far the most

abundant sphingolipid. It can comprise as much as 50% of the lipids in certain tissues,

though it is usually lower in concentration than phosphatidylcholine


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Ether glycerophospholipids Possess an ether linkage instead of an acyl group at the

C-1 position of glycerol PAF ( platelet activating factor)

A potent mediator in inflammation, allergic response and inshock (also responsible for asthma-like symptom

The ether linkage is stable in either acid or base

Plasmalogens: cis a,b-unsaturated ethers

The alpha/beta unsaturated ether can be hydrolyzed more easily


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Ether glycerophospholipids

H2C CH

O

CH2

O

O

P

O

-O O

C O

CH3

CH2

CH2

N

CH3

CH3

CH3

platelet activating factor or PAF

H2C CH

O

CH2

O

O

P

O

-O O

C O

CH2 CH2 N

CH3

CH3

CH3

A choline plasmalogen

H

H


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glycolipids

NH

O

HO R

R'

O

SUGAR polar head is a suga

beta linkage

There are different types of glycolipids: cerebrosides, gangliosides,

lactosylceramides


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GLYCOLIPIDS Cerebrosides

One sugar molecule Galactocerebroside in neuronal membranes Glucocerebrosides elsewhere in the body

Sulfatides or sulfogalactocerebrosides A sulfuric acid ester of galactocerebroside

Globosides: ceramide oligosaccharides Lactosylceramide

2 sugars ( eg. lactose) Gangliosides

Have a more complex oligosaccharide attached Biological functions: cell-cell recognition; receptors for

hormones


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Gangliosides complex glycosphingolipids that consist of a ceramide

backbone with 3 or more sugars esterified,one of thesebeing a sialic acid such as N-acetylneuraminic acid

common gangliosides: GM1, GM2, GM3, GD1a, GD1b, GT1a,GT1b, Gq1b


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Ganglioside nomenclature letter G refers to the name ganglioside

the subscripts M, D, T and Q indicate mono-, di-, tri,and quatra(tetra)-sialic-containing gangliosides

the numerical subscripts 1, 2, and 3 designate thecarbohydrate sequence attached to ceramide


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Ganglioside nomenclature Numerical subscripts:

1. Gal-GalNAc-Gal-Glc-ceramide

2. GalNAc-Gal-Glc-ceramide

3. Gal-Glc-ceramide


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O

CH 2OH

H OH

H

OH

OH

O

O

CH 2OH

H NH

H

OH

O

CH 2OH

H OH

H

H

O

CH 2OH

H OH

H

H

OH H

O

H

O

O

CH 2HC

HC

NH

C O

R

HO

C

C

O

O

C O

CH 3

NH

H

CHOH

CHOH

OH

CH 2OH

H

H

COO-C

O

H3C

H

H

H

H

D-Galactose

N-Acetyl-D-galactosamine D-galactose D-glucose

N-acetylneuraminidate (sialic acid)

A ganglioside (GM1)


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Cardiolipids

C

H2C O

O

H2C O P

O

OH

O

C

O

R1

C

O

R2

CH2 C

OH

H

CH2 O P O

OH

O

CH2

C OH

CH2O

C

O

R3

C

O

R4

H

glycerolglycerol

glycerol

A polyglycerol phospholipid; makes up 15% of total lipid-phosphorus

content of the myocardiumassociated with the cell membrane

Cardiolipids are antigenic and as such are used in serologic test for

syphilis (Wasserman test)


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Sulfolipids also called sulfatides or cerebroside sulfates

contained in brain lipids

sulfate esters of cerebrosides present in low levels in liver, lung, kidney, spleen,

skeletal muscle and heart

function is not established


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Lipid storage diseases also known as sphingolipidoses

genetically acquired

due to the deficiency or absence of a catabolic enzyme

examples: Tay Sachs disease

Gauchers disease

Niemann-Pick disease

Fabrys disease

http://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htm
http://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htmhttp://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htmhttp://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htmhttp://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htm


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Genetic defects in ganglioside metabolism leads to a buildup of gangliosides (ganglioside GM2) in

nerve cells, killing them

NAcGal Gal Gal Glu

NAcNeu

enzyme that hydrolyzes here (beta hexosaminod

is absent in Tay-Sachs disease


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Tay-Sachs disease a fatal disease which is due to the deficiency of

hexosaminidase A activity accumulation of ganglioside GM2 in the brain of

infants mental retardation, blindness, inability to

swallow a cherry red spot develops on the macula

(back of the the eyes) Tay-Sachs children usually die by age 5 and

often sooner


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Genetic defects in globoside metabolism Fabrys disease:

Accumulation of ceramide trihexoside in kidneys of patientswho are deficient in lysosomal a-galactosidase A sometimes

referred to as ceramide trihexosidase Skin rash, kidney failure, pains in the lower extremities

Now treated with enzyme replacement therapy: agalsidasebeta (Fabrazyme)


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Genetic defects in cerebroside metabolism Krabbes disease:

Also known as globoid leukodystrophy Increased amount of galactocerebroside in the white matter of the brain Caused by a deficiency in the lysosomal enzyme galactocerebrosidase

Gauchers disease: Caused by a deficiency of lysosomal glucocerebrosidase Increase content of glucocerebroside in the spleen and liver Erosion of long bones and pelvis Enzyme replacement therapy is available for the Type I disease

(Imiglucerase or Cerezyme) Also miglustat (Zavesca) an oral drug which inhibits the enzyme

glucosylceramide synthase, an essential enzyme for the synthesis ofmost glycosphingolipids


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Miglustat (Zavesca)


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Genetic defects in ganglioside metabolism Metachromatic leukodystrophy

accumulation of sulfogalactocerebroside (sulfatide) in the centralnervous system of patient having a deficiency of a specific

sulfatase mental retardation, nerves stain yellowish-brown with cresyl

violet dye (metachromasia)

Generalized gangliosidosis

accumulation of ganglioside GM1 deficiency of GM1 ganglioside: b-galactosidase

mental retardation, liver enlargement, skeletal involvement


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Niemann-Pick disease principal storage substance: sphingomyelin which

accumulates in reticuloendothelial cells

enzyme deficiency: sphingomyelinase

liver and spleen enlargement, mental retardation


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Blood groups

determined by various glycolipids on RBCs

A antigens

B antigens

H antigens

AcN Gal

L-Fucose

Ac

N Glu-sphingosine

Gal Gal NAc-Glu-sphingosine

L-Fucose

Gal NAc--Glu-sphingosine

L-Fucose

not recognized by anti-A or anti-B antibodies

(found on type O blood cells)


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Cholesterol and cholesterol esters

CH3

CH3

H

OH

H3C

HH

hydrophillic

hydrophobic

OR

O

usually palmitate

drawn this way


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STEROID NUMBERING SYSTEM

A B

C D1

2

3

45

6

7

89

10

11

12

13

14 15

16

17

18

19


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STEREOCHEMISTRY OF STEROIDSCH3 CH3H

H

H

H

CH3CH3

HH

H

H

H

H

CH3

OH

CH3

O

O

HO

H

H

H

CH3

H

CH3


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Cholesterol sources, biosynthesis

and degradation diet: only found in animal fat

biosynthesis: primarily synthesized in the liver fromacetyl-coA; biosynthesis is inhibited by LDL uptake

degradation: only occurs in the liver


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HO

HH

H

O

HH

H

R

O

usually palmitate

The hydroxyl at C-3 is hydrophilic; the rest of the

molecule is hydrophobic; also 8 centers of asymmetry


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HO

HH

Functions: -serves as a component of membranes of cells (increases or

moderates membrane fluidity

-precursor to steroid hormones

-storage and transportcholesterol esters


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Functions of cholesterol serves as a component of membranes of cells

(increases or moderates membrane fluidity)

precursor to steroid hormones and bile acids

storage and transport cholesterol esters


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Prostaglandins and other

eicosanoids (prostanoids) local hormones, unstable, key mediators of

inflammation

derivatives of prostanoic acid

COOH

20

8

12

prostanoic acid

9

1115

O


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O R

O

O

P

O

O

O-

X

O

COOH

CH3

phospholipase A2 (enzyme that hydrolyzes

at the sn-2 position - inhibit

indirectly by corticosteroids

H20

prostaglandin synthase

(also k nown as cyclooxygenase)

O

O

COOH

OH

very unstable

bond

PGH2

COX is inhibibited by

aspirin and other NSAIDs


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O

O

COOH

OH

PGH2

COOH

OH

O

HO

COOH

OHHO

HO

PGE2 PGF2akey mediator of inflammation

O

R1

O

R1

O

R1 R

HO


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R2 R2

PGA PGB

1

R2

PGC

R1

R2

O

PGD

R1

R2

O

HO

R1

R2

HO

HO

R1

R2

O

O

PGE PGFa PGG and PGHR2

HO

O

R1

R1

R2

O

PGJ

R1

R2

O

O

PGK

PGI

O

O

R1

R2 O

R1

R2HO

OH

TXA TXB

SUBSTITUTION PATTERN OF PROSTANOIDS


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Prostacyclins, thromboxanes and

leukotrienes PGH2 in platelets is converted to thromboxane A2

(TXA2) a vasoconstrictor which also promotesplatelet aggregation

PGH2 in vascular endothelial cells is converted toPGI2, a vasodilator which inhibits plateletaggregation

Aspirins irreversible inhibition of platelet COXleads to its anticoagulant effect


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Functions of eicosanoids Prostaglandins particularly PGE1 block gastricproduction and thus are gastric protection agents

Misoprostol (Cytotec) is a stable PGE1 analog that

is used to prevent ulceration by long term NSAIDtreatment

PGE1 also has vasodilator effects Alprostadil (PGE1) used to treat infants with

congenital heart defects Also used in impotance (Muse)


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Functions of eicosanoids PGF2a causes constriction of the uterus

Carboprost; Hebamate (15-Me-PGF2a) inducesabortions

PGE2 is applied locally to help induce labor at term


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Examples of drugs derived from prostaglandins


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C5H11

HS

Cys

gGlu

OH

COOH

LEUKOTRIENE F 4 (LTF4)

C5H11

HS

Cys

OH

COOH

Gly

gGlu

LEUKOTRIENE C 4 (LTC4)

Leukotrienes are derived from arachidonic acid via the enzyme5-lipoxygenase which converts arachidonic acid to 5-HPETE

(5-hydroperoxyeicosatetranoic acid) and subsequently by

dehydration to LTA4

peptidoleukotrienes

Leukotrienes

Leukotrienes


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C5H

11

HS

Cys

OH

COOH

LEUKOTRIENE E 4 (LTE4)

C5H11

HS

Cys

OH

COOH

Gly

LEUKOTRIENE D 4 (LTD4)

Leukotrienes are synthesized in neutrophils, monocytes, macrophages,

mast cells and keratinocytes. Also in lung, spleen, brain and heart.A mixture of LTC4, LTD4 and LTE4 was previously known as the

slow-reacting substance of anaphylaxis

peptidoleukotrienes

Leukotrienes


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C5H11

COOH

O

LEUKOTRIENE A 4 (LTA4)C5H11

HO

COOH

OH

LEKOTRIENE B 4 (LTB4)

Non-peptidoleuktrienes: LTA4 is formed by dehydration of

5-HPETE, and LTB4 by hydrolysis of the epoxide of LTA4

Leukotrienes


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Biological activities of leukotrienes

1. LTB4 - potent chemoattractent- mediator of hyperalgesia- growth factor for keratinocytes

2. LTC4 - constricts lung smooth muscle

- promotes capillary leakage1000 X histamine

3. LTD4 - constricts smooth muscle; lung- airway hyperactivity

- vasoconstriction4. LTE4 - 1000 x less potent than LTD4

(except in asthmatics)


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Leukotriene receptor antagonists

Montelukast

(Singulair)

Zafirlukast

(Accolate)


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Lipid-linked proteins Lipid-linked proteins (different from lipoproteins)

lipoproteins that have lipids covalently attached to them

these proteins are peripheral membrane proteins


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Lipid-linked proteins 3 types are most common:

Prenylated proteins

Farnesylated proteins (C15 isoprene unit)

Geranylgeranylated proteins (C20 isoprene unit)

Fatty acylated proteins

Myristoylated proteins (C14)

Palmitoylated proteins (C16)


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Lipid-linked proteins glycosylphosphatidylinositol-linked proteins (GPI-

linked proteins)

occur in all eukaryotes, but are particularly abundant in

parasitic protozoa located only on the exterior surface of the plasma

membrane



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Prenylated proteins


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y p

GPI-linked proteins


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Lipoproteins particles found in plasma that transport lipidsincluding cholesterol

lipoprotein classes chylomicrons: take lipids from small intestine through lymph

cells

very low density lipoproteins (VLDL)

intermediate density lipoproteins (IDL)

low density lipoproteins (LDL)

high density lipoproteins (HDL)

Terpenes


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Lipoprotein

class

Density

(g/mL)

Diameter

(nm)

Protein %

of dry wt

Phosphol

ipid %

Triacylglycerol

% of dry wt

HDL 1.063-1.21 515 33 29 8

LDL 1.019

1.063

1828 25 21 4

IDL 1.006-1.019 25 - 50 18 22 31

VLDL 0.951.006 30 - 80 10 18 50

chylomicrons < 0.95 100 - 500 1 - 2 7 84

Composition and properties of human lipoproteins

most proteins have densities of about 1.31.4 g/mL and lipid aggregates usually

have densities of about 0.8 g/mL

Lipoprotein structure


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Lipoprotein structure


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LDL molecule


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The apolipoproteins major components of lipoproteins often referred to as aproteins

classified by alphabetical designation (A thru E)

the use of roman numeral suffix describes theorder in which the apolipoprotein emerge fromachromatographic column

responsible for recognition of particle by receptors


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HELICAL WHEEL PROJECTION OF A PORTION OF

APOLIPOPROTEIN A-I


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LIPOPROTEINS spherical particles with a hydrophobic core (TG and

esterified cholesterol)

apolipoproteins on the surface large: apoB (b-48 and B-100) atherogenic

smaller: apoA-I, apoC-II, apoE

classified on the basis of density and electrophoreticmobility (VLDL; LDL; IDL;HDL; Lp(a)


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Apoproteins of human lipoproteinsA-1 (28,300)- principal protein in HDL

90 120 mg% in plasma

A-2 (8,700) occurs as dimer mainly in HDL 30 50 mg %

B-48 (240,000) found only in chylomicron


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Apoproteins of human lipoproteins C-1 (7,000) found in chylomicron, VLDL, HDL

4 7 mg %

C-2 (8,800) - found in chylomicron, VLDL, HDL

3 8 mg % C-3 (8,800) - found in chylomicron, VLDL, IDL, HDL

8 15 mg %

D (32,500) - found in HDL 8 10 mg %

E (34,100) - found in chylomicron, VLDL, IDL HDL 3 6 mg %


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Major lipoprotein classes chylomicrons

density


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Major lipoprotein classesVLDL

density >1.006

diameter 30 - 80nm

endogenous triglycerides

apoB-100, apoE, apoC-II/C-III

prebeta in electrophoresis


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Major lipoprotein classes IDL (intermediate density lipoproteins)

density: 1.006 - 1.019

diameter: 25 - 35nm

cholesteryl esters and triglycerides

apoB-100, apoE, apoC-II/C-III

slow pre-beta


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Major lipoprotein classes HDL (high density lipoproteins)

density: 1.063-1.210

diameter: 5-12nm

cholesteryl esters and phospholipids

apoA-I, apoA-II, apoC-II/C-III

alpha (electrophoresis)


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Major lipoprotein classes LDL (low density lipoproteins)

density: 1.019 - 1.063

diameter: 18-25nm

cholesteryl esters

apoB-100

beta (electrophoresis)

< 130 LDL cholesterol is desirable, 130-159 is borderlinehigh and >160 is high

Photograph of an arterial plaque


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The LDL receptor characterized by Michael Brown and Joseph

Goldstein (Nobel prize winners in 1985)

based on work on familial hypercholesterolemia

receptor also called B/E receptor because of itsability to recognize particles containing both aposB and E

activity occurs mainly in the liver

receptor recognizes apo E more readily than apo B-100


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Representation of the

LDL receptor


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Terpenes simple lipids, but lack fatty acid component

formed by the combination of 2 or more moleculesof 2-methyl-1,3-butadiene (isoprene)

monoterpene (C-10) made up of 2 isoprene units

sesquiterpene (C-15) made up of 3 isoprene units

diterpene (C-20) made up of 4 isoprene units


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Monoterpenes

limonene

CHO

citronellal

OH

menthol camphene

Monoterpenes are readily recognized by their characterisitic flavors

and odors ( limonene in lemons, citronellal in roses and geraniums,

pinene in turpentine and menthol from peppermint


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Sesquiterpenes

bisabolene

HO

eudesmol


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Diterpenes

CH 2OH

HO

H

H

OH

COOHC

O

CH 3

O

phytol gibberelic acid

CH 3 CH 3H3C

CH 3

CH 3

O

H

All-trans-retinal


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Triterpenes

Triterpenes are C-30 compounds are addition products of 2 sesquiterpenes;

Both squalene and lanosterol are precursors of cholesterol and other steroids

HO

H

squalene lanosterol


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Other terpenes tetraterpenes (C-40) are not as common as mono,

di, and triterpenes include the carotenoids such as beta-carotene

(precursor of vitamin A) and lycopene found in

tomatoes usually colorful compounds due to highly conjugated

system

polyisoprenoids or polyprenols consist of

numerous isoprene adducts (8 22) examples include dolichol phosphate, undecaprenylalcohol (bactoprenol) and the side chains of vitamins K,

vitamin E and coenzyme Q

Lec 4 Lipids

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