Lipids (McM chapt 27)Naturally occuring, lipophilic comp.

•Wax, fat oils•Soaps•Phopholipids•Prostaglandins•Terpenoids•Stereoids

Wax, fat, oils: Derivatives of fatty acids (carboxylic acids)

O

OH

Ex saturated fatty acid: Stearic acid (C18)

O

OH

Ex unsaturated fatty acid: oleic acid (C18)

O

OH

linoleic acid (C18)

ΩΩ-6

Wax: esters between fatty acid and long chain alchohol

Fat (solid), oil (liquid) - Soaps

Basic ester hydrol. - Saponifications

O

O Na

Hydrophilic headLipophilic tail

Ca 2+ - “Hard water” Ca(OCOR)2 (s)

Cationic soaps

O

O

O

R

O

R''

Triglycerides

NaOH (aq)OH

OH

O

R

O

R''

O

R'

Glycerol

O

O

ONa

Na

Na

Soaps

HOO

O

R'

Phospholipids

Extracellular fluid

Intracellular fluid

Cell membranePassive diffusion: Small, lipophilic

O

O

O

R

P

O

Glycerophospholipids

O

O

R'

R: saturated

R': unsatur.O

O (CH2)2NR3

R: H, Me

Diester Phosphoric acid

O P

O

O

O

R'O

O (CH2)2NR3

O

O

R

Hydrophilic head

2 Lipophilic tails

Sphingomyelins

OH

NH2

OH

(CH2)12CH3

Sphingosine

O

NHCO(CH2)nCH3

OH

(CH2)12CH3

n: 16-24

P

O

(CH2)2NH2R3

O

coating of nerve fibers

Prostaglandins etc

Subtypes COXCOX-1: Synth of essential prostagland.COX-2: Active only under inflamations

CO2H158

11 14

20

Arachidonic acid

Cyclooksygenase(COX)5

15CO2H

OO

Prostglandin H2(PGH2)

Tromboxanes

Prostaglandines

Prostasyklines

Many different biolog. effectsInflamations, allergy responce

Inhib. by many pain killers

RofecoxibVioxx®

Avreg 2004

COX2/COX2: 35

SO

O

OO

COX2 inhibitorsCoxibes

Terpenoids

O

Isopentenylpyrophosphate

(C-5)

P PO P P

O

P

OOH

3 ATPOH

HO

OHO

Mevalonate(C-6)

N

N N

N

NH2

OO

OHHO

PO

OHOP

O

OHOP

O

OHHO

ATP, Adenosine-5'-triphosphate

P

C-10: MonoterpenesC-15: SesquiterpenesC-20: DiterpenesC-25: SesterterpenesC-30: Triterpenes

O

(+) Camphor α-Pinene β-Pinene

O

Isopentenylpyrophosphate

(C-5)

P PRearrange

O

Dimethylallylpyrophosphate

(C-5)

P PO P P

HO

trans-Geranylpyrophosphate

(C-10)

P P

OH

trans-Geraniol

OH

(-)−β-citronellol (-) Linalool

OH

OH

(+)-α-Terpineol (-)-Menthol

HO

(+)-Carvone

O

OH

Thymol

O

trans, trans-Farnesylpyrophosphate(C-15)

P P OPP+

tail to tail coupling

Squalene (C-30)

O

HO

Lanosterol

H

Squaleneepoxidase

Enzyme-Nu

H

HOH

H

Enz--Nu

H

Squalene epoxide cyclase

H

B All stereoids

Stereoids

A B

C D1

2

3

45

6

7

8

910

11

1213

14 15

16

1717β 17α

B / C og C / D always trans

10β

5α

A / B trans fused

10β

A / B cis fused

5α

Sex Hormones

H

HHO

Testosterone

OH

5α-reduktaseH

HHO

5α-Dihydrotestosterone (5DHT)More active A-B ring transCis isomer inaktive

OH

H

H

HHO

Progesterone

O

Many semisynth drugs in use (better bioavalabil .)

HO

H

HH

O

Estrone

in vivo

HO

H

HH

Estradiol

OH

HO

H

HH

Estriol

OH

in vivo

(low activity)

(fast metabol)

OH

(low activity)

Used in drugs

HO

H

HH

OH

H K

2 ekviv.

Ethinyl estradiol(only estrogen im P-pills)

Estrogens

Corticostereoids

Mineralcorticoid

O

H

H H

O

OH OOH

AldosteroneRegulation of elektrolyttic ballanceincrease re-uptake of Na (and hence H20)

Glucocorticoid

H

H H

O

O

OH

HO OH

Hydrokortison

Effect on metabolism (karbohydrates, lipids, proteins)Antiinflammatoric

Numerous semisynth. analogs as drugsVarious antiinflam. activity, mineralcorticoid side effects

Corticostereoids

Mineralcorticoid

O

H

H H

O

OH OOH

AldosteroneRegulation of elektrolyttic ballanceincrease re-uptake of Na (and hence H20)

Glucocorticoid H

H H

O

O

OH

HO OH

Hydrokortison

Effect on metabolism (karbohydrates, lipids, proteins)Antiinflammatoric

Numerous semisynth. analogs as drugsVarious antiinflam. activity, mineralcorticoid side effects