steroide cholesterol. sterane skeleton i.sterane skeleton (sterane or gonane or...
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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)