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Structure of Cholesterol
C
Steroids
A
D
B
Fundamental framework of steroids is the
tetracyclic unit shown.
Steroids
Steroid A/B and B/C Rings Resemble Decalin
Steroid B/ C, and C/D rings are trans fused
Methyl groups at C-10 and C-13 are “angular”
methyl groups
The A/B rings are usually trans fused in most naturally
occurring steroids
Cholesterol
Substituents on the same side of the steroid ring system
as the angular methyl groups are β-substituents
Those on the opposite side of the plane of the ring
system are α-substituents
Structure of Cholesterol
Structure of Cholesterol
CH3
CH3
CH3
H
CH3
CH3
CH3
CH3
H
CH3
H
H
HO
Cholesterol has the fundamental steroid
skeleton modified as shown.
CH3
CH3
H
H
HO
Some parts of the cholesterol molecule are
isoprenoid.
isoprenoid. But other parts don't obey the
isoprene rule. Also, cholesterol has 27 carbons,
which is not a multiple of 5.
Biosynthesis of Cholesterol
Biosynthesis of Cholesterol
Biosynthesis of Cholesterol
Cholesterol is biosynthesized from the triterpene
squalene.
squalene. In the first step, squalene is
converted to its 2,3-epoxide
2,3-epoxide..
Cholesterol is biosynthesized from the triterpene
squalene.
squalene. In the first step, squalene is
converted to its 2,3-epoxide
2,3-epoxide..
O2, NADH, enzyme
O
Biosynthesis of Cholesterol
Biosynthesis of Cholesterol
O
O
To understand the second step, we need to look
at squalene oxide in a different conformation,
one that is in a geometry suitable for cyclization.
cyclization.
To understand the second step, we need to look
at squalene oxide in a different conformation,
one that is in a geometry suitable for cyclization.
cyclization.
O
Biosynthesis of Cholesterol
Biosynthesis of Cholesterol
HO
Cyclization is triggered by epoxide ring opening.
H
+
+
Cyclization is triggered by epoxide ring opening.
O
H
+
O
Biosynthesis of Cholesterol
Biosynthesis of Cholesterol
••
• OH
•
2
H
The product of this rearrangement is a
triterpene called lanosterol.
lanosterol. A number of
enzyme-catalyzed steps follow that convert
lanosterol to cholesterol.
+
HO
H
H
Loss of a proton is accompanied by a series of
hydride shifts and methyl migrations.
H
H
HO
HO
H
H
Cholesterol
Cholesterol is the biosynthetic precursor to a
large number of important steroids:
Bile acids
Vitamin D
Corticosteroids
Sex hormones
Vitamin D
Cholesterol
7-Dehydrocholesterol
7-Dehydrocholesterol
CH3
CH3
CH3
H
CH3
CH3
CH3
CH3
H
Cholesterol is the precursor to vitamin D.
Enzymes dehydrogenate cholesterol to introduce a second
double bond in conjugation with the existing one. The
product of this reaction is called 7-dehydrocholesterol
7-dehydrocholesterol..
CH3
CH3
H
H
HO
CH3
H
HO
Sunlight converts 7-dehydrocholesterol
7-dehydrocholesterol on the
skin's surface to vitamin D3.
Vitamin D3
CH3
CH3
CH3
CH3
Bile Acids
H
HO
Insufficient sunlight can lead to a deficiency of
vitamin D3, interfering with Ca2+ transport and
bone development. Rickets can result.
Cholesterol
Cholic Acid
O
CH3
CH3
CH3
CH3
H
H
HO CH3
CH3
CH3
CH3
H
H
HO
HO
Oxidation in the liver degrades the cholesterol side chain
and introduces OH groups at various positions on the
steroid skeleton. Cholic acid is the most abundant of the
bile acids.
H
H
OH
H
Salts of cholic acid amides (bile
(bile salts),
salts), such as sodium
taurocholate,
taurocholate, act as emulsifying agents to aid digestion.
Sodium Taurocholate
O
HO CH3
CH3
CH3
H
HO
Corticosteroids
OH
H
NHCH 2CH2SO3Na
H
H
OH
Cholesterol
Cortisol
CH3
CH3
CH3
HO
CH3
CH3
H
H
O
CH3
CH3
H
H
HO
OH
OH
H
H
O
Enzymatic degradation of the side chain and oxidation of
various positions on the steroid skeleton convert cholesterol
to corticosteroids.
corticosteroids.
Cortisol is the most abundant of the corticosteroids.
Enzyme-catalyzed oxidation of cortisol gives cortisone.
Cortisone
O
CH3
O
CH3
OH
OH
H
Sex Hormones
H
H
O
Corticosteroids are involved in maintaining electrolyte
levels, in the metabolism of carbohydrates, and in
mediating the allergic response.
Testosterone
H3C
H3C
Estradiol
OH
H3C
H
H
OH
H
H
O
Testosterone is the main male sex hormone.
H
H
HO
Estradiol is a female sex hormone involved in
regulating the menstrual cycle and in reproduction.
Progesterone
O
H3C
H3C
H
H
H
O
Supresses ovulation during pregnancy.
Synthetic Steroids