Transcript Biosynthesis of Steroids from Squalene

Lipids
Broadly defined as
naturally occurring nonpolar compounds having
simple functional groups.
Major Categories of Lipids






Fats and Oils
• Biosynthesis of fatty acids
Phospholipids
Waxes
Terpenes
Steroids
Prostaglandins
Fats


Esters of fatty (long chain carboxylic) acids
Common are triacyl glycerols, which can be
hydrolyzed (saponified) into soaps:
O
CH2OC
O
CH2O2C
CHOC
CHOO
2C
CH
CH
2O2C
2OC
aq. NaOH
Soap (mixture of salts of fatty acids):
CH2OH
CHOH
CH2OH
+
C13H27CO2 Na
+
C15H31CO2 Na
+
C17H35CO2 Na
Micelles: mode of action of soap
Na O
O
Soap (above) can be represented as:
P
Soap (and detergents) form spherical clusters
(right) called micelles; micelles surround
and dissolve non-polar substances (oily
stains) and render them “soluble.”
H2O
H2O
P
H2O
P
P
P
H2O
P
P
P
P
H2O
P
P
P
P
P
Oil
P
P
P
H2O
P
P
P
P
P
P
P
P
Oils (polyunsaturated fats)
O
O
CH2OC
CO CH
O
CH2OC
Presence of cis double bonds in oils makes it difficult
for the molecules to pack regularly in a solid structure;
oils have lower melting points than fats, and are liquids at RT.
Biosynthesis of Fatty Acids
Repetitive applications of thio-Claisen
reactions; explains why most fatty acids
have an even number of carbon atoms
Enolization / Carboxylation
of Acetyl Coenzyme A
O
O
H
CH3CSCoA
CH2=CSCoA
(acetyl CoA, a 2 C unit)
(enol form)
+
H
O
C
O
O
H
CH2=CSCoA
O
O
HOCCH2CSCoA
(malonyl CoA)
Acylation of Malonyl Coenzyme A
with 2 Carbon unit
O
CH3C
O
S synthase
O
O
O
H
HOCCH=CSCoA
HOCCH2CSCoA
(malonyl CoA)
O
O
CH3CCHCSCoA
C
HO
O
Enol form
Decarboxylation, Reduction,
Dehydration and Reduction
O
O
CH3CCHCSCoA
C
HO
-CO2
O
O
CH3CCH2CSCoA
[H] (NADPH)
O
OH
O
CH3CHCH2CSCoA
-H2O
O
CH3CH2CH2CSCoA
(a 4 Carbon unit)
[H]
O
CH3CH=CHCSCoA
(NADPH)
Acylation of Malonyl Co A
with 4 carbon unit
O
CH3CH2CH2C
O
S synthase
(4 carbon unit)
O
HOCCH2CSCoA
O
O
H
HOCCH=CSCoA
(malonyl CoA)
O
O
CH3CH2CH2CCHCSCoA
C
HO
O
Conversion to 6 carbon unit
O
O
CH3CH2CH2CCHCSCoA
C
HO
O
decarboxylation,
reduction of C=O
dehydration
reduction of C=C
O
CH3CH2CH2CH2CH2CSCoA
(6 carbon unit)
Acylation of Malonyl Co A
with 6 carbon unit
O
CH3CH2CH2CH2CH2C
O
S synthase
O (6 carbon unit)
HOCCH2CSCoA
O
O
H
HOCCH=CSCoA
(malonyl CoA)
O
O
CH3CH2CH2CH2CH2CCHCSCoA
C
HO
O
Conversion to 8 carbon
unit...etc.
O
O
decarboxylation,
CH3CH2CH2CH2CH2CCHCSCoA reduction of C=O
dehydration,
C
reduction of C=C
O
HO
O
CH3CH2CH2CH2CH2CH2CH2CSCoA
(8 carbon unit)
Common Saturated Fatty Acids
CO2H
C14 Myristic Acid
CO2H
C16 Palmitic Acid
CO2H
C18 Stearic Acid
Common Unsaturated Fatty Acids
O
C
OH
Palmitoleic
O
C
OH
Oleic
O
C
Linoleic
OH
Polyunsaturated Fatty Acids
Polyunsaturated fatty acids (PUFAs) include those having two
and three double bonds.
Omega-3 fatty acids are those unsaturated fatty acids that have
a double bond between the third and fourth carbon from the end
of the carbon chain (opposite the CO2H group).
A common omega-3 fatty acid found in fish oil is linolenic acid:
3
1
6
9
O
C
2
OH
Omega-3 fatty acids are considered beneficial for brain function.
Composition of Fats and Oils
lauric
C12
myristic
C14
palmitic stearic
C16
C18
oleic linoleic
C18(1)
C18(2)
Animal Fats
Lard
Beef Fat
Butter Fat
Human Fat
Whale Blubber
2
1
-
1
10
3
8
25
27
29
25
12
8
14
10
8
3
50
50
27
46
35
10
3
5
10
10
Vegetable Oils
Coconut oil
Corn oil
Olive oil
Peanut oil
Soybean oil
48
-
18
1
1
-
11
10
7
7
10
2
3
3
5
2
7
45
82
58
29
1
35
6
24
51
Fats and Oils in Nuts
Nut
g. prot./oz.
Walnuts
4
Almonds
6
Hazelnuts
4
Cashews
4
Macadamia
2
Pecans
3
Peanuts
7
g. fat/oz
18
14
17
13
22
20
14
% sat’d
10
10
9
21
16
9
16
% MUFAs
15
65
77
62
76
53
52
% PUFAs
75
25
14
17
8
28
32
Phospholipids
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Phospholipids are long-chain fatty esters of
glycerol also containing a phosphoric acid
derivative.
They contain a glycerol backbone, like fats and
oils, but they have a phosphate group with an
ionic alkyl ammonium group also attached.
Representative Phospholipids
O
O
O
R'
CH2O C
C O C
H
O
CH2O
P
O
R
R'
CH2O C
C O C
O CH2CH2N(CH3)3
H
O
CH2O
P
O CH2CH2NH3
O
O
Phosphatidylcholine
(lecithin)
R
Phosphatidylethanolamine
(cephalin)
O
C O CH2
O
C O C
H
O
CH2O P
O
O CH2CH2N(CH3)3
Phospholipids…
O
C O CH2
O
C O C
H
O
CH2O P
O
Can be represented as:
P
O CH2CH2N(CH3)3
Lipid Bilayer of Cell Membranes
Outside the cell (aqueous)
P
P
P
P
P
P
P
Cell membrane
P
P
P
P
P
P
P
Inside the cell (aqueous)
Waxes

Long chain esters of long chain fatty acids
Waxes:
CH3(CH2)mCO2(CH2)nCH3
m = 8 - 18
n= 15 - 35
O
O
(present in beeswax)
Terpenes

Derived biosynthetically from a branched five
carbon unit, isopentenyl pyrophosphate:
O
O
O
P
P
O
O
O
isopentyl pyrophosphate
isopentenyl
pyrophosphate
O
isoprene
Terpenes...

Common monoterpenes (C10):
OH
OH
CH2OH
CHO
geraniol
citral
menthol
Some more common terpenes
O
H
O
H
citronellal
(oil of citronella)
limonene
(lemons)
zingiberene
(ginger)
a sesquiterpene; 15 Cs
Steroids

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Involved in regulatory processes and in sexual
characteristics and functions
Common steroids include cholesterol, estradiol,
testosterone, estrone and progesterone
CH3
CH3
A
B
C
R
CH3
D
CH3
C
A
B
R
D
Some Common Steroids
CH3 O
CH3OH
H
CH3
H
H
O
CH3
H
testosterone
H
H
HO
H
androsterone
CH3 O
CH3 OH
H
H
HO
H
H
H
HO
estrone
estradiol
H
…More Common Steroids
OH
CH3 C
OH
CH3 C
CH
H
H
H
H
H
H
HO
H
O
norethrindrone
ethynylestradiol
O
CH3 C
CH3
CH3
CH3
H
H
O
progesterone
CH3
H
H
H
HO
cholesterol
H
H
CH
…More Common Steroids
O
CH3 C
O
CH3
CH2OH
OH
CH3
OH
H
H
O
CH3
H
H
HO
cortisone
H
H
H
OH
cholic acid
CO2H
H
Prostaglandins

C20 carboxylic acids that contain a 5-member
ring and have two long side chains.

They were first isolated from prostate glands of
sheep, but now they are known to have
widespread distribution among tissues, and to
exhibit an extraordinarily wide range of biological
effects.
Representative Structures
CO2H
Biosynthetic source:
arachidonic acid
O
H
CO2H
HO H H
CO2H
HO
H
HO
H
Prostaglandin E1 (PGE1)
HO
H
HO
H
Prostaglandin F2a (PGF2a)
Some Varied Biological
Effects of Prostaglandins
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Lower blood pressure
Affect clotting of blood
Lower gastric secretions
Promote inflammation (countered by aspirin,
which inhibits PG biosynthesis)
Affect reproductive systems
Stimulate uterine contractions during childbirth
Final Exam
Review:
A review session are scheduled for class on
Monday, April 26 in DO 205. Bring questions,
and bring the last 4 sheets of the Course-Pack.
Final Exam:
Monday, May 3, 8:00 am – 11:00 am
(Dobo Hall, Room 205)