Steroide Cholesterol. Sterane skeleton I.Sterane skeleton (sterane or gonane or perhydrocyclopentanophenanthrene) Sterane Sterane R=Q=CH 3, Z=H, long.

SteroideSteroide

CholesterolCholesterol

Sterane skeletonSterane skeleton

I. Sterane skeleton (sterane or gonane or perhydrocyclopentanophenanthrene)

Q Z

R

A B

C D1

2

34

56

7

89

10

1112

13

14 1516

17

SteraneSterane R=Q=CH3, Z=H, long alkyl, etc.

ClassificationClassification

II. Classification

a. Sterols (zoosterols as cholesterol,

phytosterols and mycosterols

b. Steroid vitamines (vitamin D group)

c. Sex hormones (estrogens, gestagens as

progesterone, androgens as testosterone)

d. Corticosteroids (cortisol, aldosteron)

e. Cardiac glycosides (strophantin, digitoxin)

f. Steroid alkaloids (solanidine, tomatidine)

ZoosterolsZoosterols

Cholesterol

Occurrence: In the tissues of vertebrates, the

main sterol is cholesterol (Greek, chole, bile),

abundant in adrenals (10%, w/w), nervous tissues

(2%,w/w), liver (0.2%,w/w) and gall stones.

Isolation (1770 Poulletier de La Salle) from gall

stones; (1815 M.E. Chevreul) from the

unsaponifiable fraction of animal fats

(cholesterol=Greek, khole, bile and stereos,

solid).

Cholesterol ICholesterol I

Gallstones containing cholesterolGallstones containing cholesterol

Cholesterol IICholesterol II20

19

1817

14

11

10

75

1

HO

H3C

H3C

H3C CH3

CH3H

HH

a. Numberingb. Stereoisomerism: 28 stereoisomers, cholesterol is

one of the isomers.

c. Relative configuration: C-10-CH3 group serves as

reference point for stereochemical designation. (The ringsystem is approximately planar.)

Cholesterol IIICholesterol III

Side groups

at C-10 and C-13 are above the plane of the

rings (-substituents)

indicated with a solid line.

Side groups project below the plane of the

ringsystem are designated as -substituents

indicated with a dashed line.

Cholesterol IVCholesterol IV

c. Cis or trans ring fusion (or ring junctions)

The two cyclohexane rings can be joined in either

cis or trans configuration.

They two fused cyclohexane rings can form

cis-decalin, both angular groups are on the

same side of the ring,

trans-decalin, angular groups are on opposite

sides of the ring.

Cholesterol VCholesterol V

Reduction of cholesterol

5353

Cholesterol + H2/catalyst

HO

H3C

H3C

H3C CH3

CH3H

HH

HHO

H3C

H3C

H3C CH3

CH3H

HH

H

CCholestanolholestanol CCoprostanoloprostanol

(5-cholestan-3-ol) (5-cholestan-3-ol)

A/B tr, B/C tr, C/D tr A/B cis, B/C tr, C/D tr

(Cholesterol is partly excreted in the form of sterols cholestanol and coprostanol.)

Cholesterol VICholesterol VI

d. Conformaton of steroids

conformation of cholestane (planar ringsystem)

H

R

Q

H

Z

H

In In cholestanecholestane R=Q=CH R=Q=CH33, Z=isooctyl, Z=isooctyl

In adrostane R=Q=CHIn adrostane R=Q=CH33, Z=H, Z=H

Cholesterol VCholesterol V

d. Conformaton of steroids

conformation of cholic acid

CCholic acidholic acid ( (coprostanecoprostane skeleton) skeleton)

COOH

OH

OH

H

CH3

CH3

CH3

OHH

3

7

12

H

Cholesterol VICholesterol VI

Skeletal hydrocarbons of steroids:

Cholestane, coprostane, androstane, pregnane

CH3

H

CH3CH2

CH2

H

HH

17

PregnanePregnane

Cholesterol VIICholesterol VII

2. Physical properties

Solid, its watersolubility at 25 C: 4.7 M/L

Plasma level: 3,1-5,7 mM/L in lipoprotein

complexes. (In chylomicrons, in VLDL, in LDL and in

HDL.)

In the lipoproteins about 30 % of it exists as free,

about 70 % of it exists as ester.

In the bile the cholesterol is esterified only in 4 %.

(solubilisation by phospholipids and salt of bile

acids)

Cholesterol VIIICholesterol VIII

Solubilization of Solubilization of cholesterolcholesterol (schematic figure (schematic figure of LDL)of LDL)

Atherosclerotic plaque Atherosclerotic plaque blocking most of the blocking most of the lumen of the blood lumen of the blood vessel.vessel.

Biological role of cholesterolBiological role of cholesterol

Biological role of cholesterol

Component of membranes

Precursor of the major class of steroids

Biosynthesis of cholesterol IBiosynthesis of cholesterol I

Biosynthesis of cholesterol IBiosynthesis of cholesterol III

Mycosterols (Ergosterol)Mycosterols (Ergosterol)

CH3

H3C CH3

CH3

CH3

HO

H H7

Isolation: from yeast

Importance: component of fungal membranes

Precursor of vitamin D2 (provitamin)

Vitamin D group (vitamin DVitamin D group (vitamin D22 and D and D33) I) I

Deficiency in childhood: rickets (inadequate

calcification of cartilage and bone). It was characterized

as Children’s disease of the English.

Deficiency in adults: osteomalacia (lack of

mineralization of bone with normal matrix)

Occurrence of vitamin D3 (cholecalciferol): in fish

liver oils.

Biosynthesis of vitamin D3 from 7-

dehydrocholesterol

Vitamin D group IIVitamin D group II

Biosynthesis of vitamin D3

DD22-Vitamin (ergocalciferol)-Vitamin (ergocalciferol)

CH3

H3C CH3

CH3

CH2

HO

H

DD22-Vitamin-Vitamin (Formation from ergosterol)

Bile acids IBile acids I

Biosynthesis: from cholesterol in the liver (C27 C24)

Structure: cholanic acid is parent compound of the bile acids.

Primary bile acids: cholid acid and chenodeoxycholic acid.

CH3

HO

H

CH3 H

H

OHH

O

C

H3CH

3 7

12

O2H

Cholic acidCholic acid

Bile acids IIBile acids II

Conjugated bile acids (glycocholic acid and

taurocholic acid)

Secondary bile acids – mono- and dihydroxi

derivatives (lithocholic acid and deoxycholic acid)

Physiological role: emulsification of fats

(amphoteric character)

Sex hormoneSex hormoness

Female sex hormone IFemale sex hormone I

Estrogenes

Structure: A-ring is

aromatic.OH

C

H

HH

HO

3

17

H3OC

H

HH

HO

3

17

H3

EstroneEstrone EstradiolEstradiol

Female sex hormone IIFemale sex hormone II

Production: in ovaries (and in adrenal cortex)

from androgens.

Physiological role: play pivotal role in female

reproduction, in bone metabolism and in the

maintenance of cardiovascular system.

Estradiol is more potent.

Female sex hormone IIFemale sex hormone III (Progesteron)I (Progesteron)

COC

H

HH

O

C

CH3

3

17

H3

H3

Production: in the ovaries

Physiological role: Progesterone prepares the uterus for egg implantation, maintains pregnancy, and prevents further ovulation during pregnancy.

Structure: pregnane derivative

Steroid contraceptiveSteroid contraceptive agentsagents

H

O

H

H H

OHH3C

C CH13

1719

HO

H

H H

OH

C CHC

17

H3

NorgestrelNorgestrel Ethynylestradiol

Male sex hormones IMale sex hormones I

O

H

H H

OHC

C17

H3

H3

3HO

H

H H

OC

C

H

17

H3

H3

3

TestosteronTestosteron AndrosteronAndrosteron

Male sex hormones IIMale sex hormones II

Structure: androstane skeleton

Production: in the testes (in the adrenal cortex)

Physiological role: sexual differencies in

nonreproductive system, maturation of sperms,

etc.

Testosteron is more potent.

Anabolic steroids I

Structure: androsteron or testosteron skeleton or

19-norsteroids.

O

H

H H

OHC

H

CH3

17

H3

O

H

H H

OHC

C

CH317

H3

H3

17-Methyltestosteron

Norethandrolone

Anabolic steroids = Synthetic substances related to male sex hormones. “Anabolic” refers to muscle-building.

Anabolic steroids II

Side effects: Abuse of anabolic steroids, however,

can lead to serious health problems, some

irreversible.

Corticosteroids ICorticosteroids I

Glucocorticoids: cortisol (hydrocortison)

O

H

H H

CC

C

HO

CH2OH

OOH

17

H3

H3

21

3

11

Biosynthesis from progesterone, it is a pregnane derivative.

Physiological role: synthesis of glycogens, leads to protein breakdown by cells. It ihibits inflammation and allergic resoponses.

Cortisol

MineralcorticoidsMineralcorticoids

CC

C

HO

O

HO O

CH2OH

H

H H

H311

17

18

Biosynthesis: from progesteron

Structure: pregnane derivative

Physiological role: regulates electrolyte Na+, Cl-, HCO3

- and fluid balance and the blood pressure.

AldosteroAldosteronn

Steroid Steroid aanti-nti-iinflammatory nflammatory aagentsgents

Steroid anti-inflammatory agents: derivatives of cortisol

(the effect of the glucocorticoid hormon decreased, but the

antiinflammatory and antiallergic increased)

CC

C

HO

O

CH2OH

H

F H

OOH

CH3H316

17

H3

COC

C

HO

O

CH2OH

H

H H

OH

CH3

H3

6

17

H3

MethylprednisoloMethylprednisolonene

DexamethasoDexamethasonn

Biosynthesis of steroid hormonesBiosynthesis of steroid hormones

Cholesterol (C27)

Pregnenolone (C21)

Progestagens (C21)

Glucocorticoids (C21)

Mineralocorticoids (C21)

Androgens (C19)

Estrogens (C18)

Cardiac glycosides ICardiac glycosides I

C

C

RO

H

H OH

H

OO

H3 14

17

H3

19

3 5

Digitoxin (R=glycosyl Digitoxin (R=glycosyl group)group)

Digitalis purpurea

Cardiac glycosides IICardiac glycosides II

General feature: plant steroids occurring as

glycosides in plants. Digitoxin (from Digitalis

purpurea, D. lanata), its hydrolysis yields

digitoxigenin (aglycon) and a trisaccharide.

Structure: ring fusion A/B cis, B/C tr, C/D cis, at

17 an unsaturated lactone ring.

Physiological role: heart stimulant

Cardiac glycosides IIICardiac glycosides III

C

CO

RO

H

H OH

OH

OO

H 14

17

H3

19

3 5

Strophantin (R=glycosyl Strophantin (R=glycosyl group)group)

Strophantus kombe

Cardiac glycosides ICardiac glycosides IVV

Strophantin (from Strophantus kombe) its

hydrolysis yields strophantidine (aglycon) and a

trisaccharide.

Structure: A/B cis, B/C tr, C/D cis, at C-17 an

unsaturated lactone ring, and at C-10 a formyl

group

Physiological role: heart stimulant

Steroid alkaloids ISteroid alkaloids I

Structure: they contain steroid aglycons with

heterocycylic ring, in the nature they occur as glycosides.

N

HO

C

C

H

CH3

H3C

H3

H3

1617

SolanidinSolanidin (potatoe, Solanum tuberosum)

Steroid alSteroid alkkaloids IIaloids II

HO

C

C

O

NCH3HH3C

H3

17

H3

16

Tomatidin Tomatidin (tomato, Solanum lycopersicum)

Importance of steroid alkaloids

Exotic steroids IExotic steroids I

Shark repellents (pavonines, cholesterol derivatives)

Bufotoxines (in Bufo bufo)

Exotic steroids IIExotic steroids II

Ecdysones (20-hydroxyecdysone as the major

insect moulting hormone.)

Steroid antibiotics (fusidic acid)