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26.11
Steroids: Cholesterol
Structure of Cholesterol
Fundamental framework of steroids is the
tetracyclic unit shown.
Structure of Cholesterol
CH3
CH3
CH3
H
CH3
CH3
H
H
HO
Cholesterol has the fundamental steroid
skeleton modified as shown.
Structure of Cholesterol
CH3
CH3
CH3
H
CH3
CH3
H
H
HO
Some parts of the cholesterol molecule are
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
Cholesterol is biosynthesized from the triterpene
squalene. In the first step, squalene is
converted to its 2,3-epoxide.
Biosynthesis of Cholesterol
Cholesterol is biosynthesized from the triterpene
squalene. In the first step, squalene is
converted to its 2,3-epoxide.
O2, NADH, enzyme
O
Biosynthesis of Cholesterol
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.
Biosynthesis of Cholesterol
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.
O
Biosynthesis of Cholesterol
Cyclization is triggered by epoxide ring opening.
O
H
+
Biosynthesis of Cholesterol
+
HO
Cyclization is triggered by epoxide ring opening.
O
H
+
Biosynthesis of Cholesterol
••
•• OH
2
H
+
HO
H
H
Loss of a proton is accompanied by a series of
hydride shifts and methyl migrations.
H
HO
H
Biosynthesis of Cholesterol
The product of this rearrangement is a
triterpene called lanosterol. A number of
enzyme-catalyzed steps follow that convert
lanosterol to cholesterol.
H
HO
H
Cholesterol
Cholesterol is the biosynthetic precursor to a
large number of important steroids:
Bile acids
Vitamin D
Corticosteroids
Sex hormones
26.12
Vitamin D
Cholesterol
CH3
CH3
CH3
H
CH3
CH3
H
H
HO
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
CH3
CH3
H
CH3
H
HO
Sunlight converts 7-dehydrocholesterol on the
skin's surface to vitamin D3.
Vitamin D3
CH3
CH3
CH3
CH3
H
HO
Insufficient sunlight can lead to a deficiency of
vitamin D3, interfering with Ca2+ transport and
bone development. Rickets can result.
26.13
Bile Acids
Cholesterol
CH3
CH3
CH3
H
CH3
CH3
H
H
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.
Cholic Acid
O
HO CH3
CH3
CH3
H
HO
OH
H
H
OH
H
Salts of cholic acid amides (bile salts), such as sodium
taurocholate, act as emulsifying agents to aid digestion.
Sodium Taurocholate
O
HO CH3
CH3
CH3
H
HO
H
H
OH
H
NHCH2CH2SO3Na
26.14
Corticosteroids
Cholesterol
CH3
CH3
CH3
H
CH3
CH3
H
H
HO
Enzymatic degradation of the side chain and oxidation of
various positions on the steroid skeleton convert cholesterol
to corticosteroids.
Cortisol
O
CH3
HO
CH3
H
OH
OH
H
H
O
Cortisol is the most abundant of the corticosteroids.
Enzyme-catalyzed oxidation of cortisol gives cortisone.
Cortisone
O
CH3
OH
O
CH3
H
OH
H
H
O
Corticosteroids are involved in maintaining electrolyte
levels, in the metabolism of carbohydrates, and in
mediating the allergic response.
26.15
Sex Hormones
Testosterone
H3C
H3C
OH
H
H
H
O
Testosterone is the main male sex hormone.
Estradiol
H3C
OH
H
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.
26.16
Carotenoids
Carotenoids
Carotenoids are naturally occurring pigments.
Structurally, carotenoids are tetraterpenes.
They have 40 carbons. Two C20 units are linked
in a tail-to-tail fashion.
Examples are lycopene and b-carotene.
Carotenoids
Lycopene (tomatoes)
b-Carotene (carrots)