Transcript Organic Chemistry

Lipids
Chapter 26
26-1
Lipids
 Lipids:
A heterogeneous class of naturally
occurring organic compounds classified together
on the basis of common solubility properties.
• They are insoluble in water but soluble in aprotic
organic solvents, including diethyl ether, methylene
chloride, and acetone.
 Lipids
include:
• triglycerides, phospholipids, prostaglandins,
prostacyclins, and fat-soluble vitamins.
• cholesterol, steroid hormones, and bile acids.
26-2
Triglycerides
 Triglyceride:
An ester of glycerol with three fatty
acids.
Saponification
O
O CH2 OCR
R'COCH
O
CH2 OCR''
A triglyceride
1 . NaOH, H2 O
2 . HCl, H2 O
RCOOH
CH2 OH
HOCH
CH2 OH
+
1,2,3-Prop anetriol
(Glycerol, glycerin)
R'COOH
R''COOH
Fatty acids
26-3
Fatty Acids
 Fatty
acid: A carboxylic acid derived from
hydrolysis of animal fats, vegetable oils, or
membrane phospholipids.
• Nearly all have an even number of carbon atoms, most
between 12 and 20, in an unbranched chain.
• The three most abundant are palmitic (16:0), stearic
(18:0), and oleic acid (18:1), where the first number is
the number of carbons and the second is the number
of double bonds in the hydrocarbon chain.
• In most unsaturated fatty acids, the cis isomer
predominates; the trans isomer is rare.
• Unsaturated fatty acids have lower melting points than
their saturated counterparts; the greater the degree of
unsaturation, the lower the melting point.
26-4
Fatty Acids
 The
most common fatty acids.
C arbon Atoms : C omm on
Dou ble Bon ds Name
Me l ti n g Poin t
(°C )
Saturated Fatty Acids
Higher
mp
12:0
14:0
16:0
18:0
20:0
Lau ri c aci d
Myri s ti c aci d
Palm itic acid
Stearic acid
Arach i di c aci d
44
58
63
70
77
Unsatur ated Fatty Aci ds
Lower
mp
16:1
18:1
18:2
18:3
20:4
Palm itol e ic acid
Ol ei c aci d
Li nol e ic acid
Li nol e ni c acid
Arach i don i c aci d
1
16
-5
-11
-49
26-5
Triglycerides
 Physical
properties depend on the fatty acid
components.
• Melting point increases as the number of carbons in its
hydrocarbon chains increases and as the number of
double bonds decreases.
• Oils: Triglycerides rich in unsaturated fatty acids are
generally liquid at room.
• Fats: Triglycerides rich in saturated fatty acids are
generally semisolids or solids at room temperature.
26-6
Triglycerides
• example: a triglyceride derived from one molecule
each of palmitic acid, oleic acid, and stearic acid, the
three most abundant fatty acids in the biological world.
p almitate (16:0)
O
oleate (18:1)
O CH2 OC(CH2 ) 1 4 CH3
stearate (18:0)
CH3 ( CH2 ) 7 CH=CH(CH2 ) 7 COCH O
CH2 OC(CH2 ) 1 6 CH3
26-7
Triglycerides
 The
lower melting points of triglycerides rich in
unsaturated fatty acids are related to differences
in their three-dimensional shape.
• Hydrocarbon chains of saturated fatty acids can lie
parallel with strong dispersion forces between their
chains; they pack into well-ordered, compact
crystalline forms and melt above room temperature.
• Because of the cis configuration of the double bonds
in unsaturated fatty acids, their hydrocarbon chains
have a less ordered structure and dispersion forces
between them are weaker; these triglycerides have
melting points below room temperature.
26-8
Soaps and Detergents
 Natural
soaps are prepared by boiling lard or
other animal fat with NaOH, in a reaction called
saponification (Latin, sapo, soap).
O
O CH2 OCR
s apon ifi cation
+
3
N
aOH
RCOCH
O
CH2 OCR
CH2 OH
A trigl yce ride
(a trie s te r of glyce rol )
CHOH
+
O
+
3 RCO N a
S odiu m soaps
CH2 OH
1,2,3-Propan etriol
(Glycerol; G lyceri n)
COO-Na+
26-9
Soaps and Detergents
 Soaps
clean by acting as emulsifying agents:
• Their long hydrophobic hydrocarbon chains are
insoluble in water and tend to cluster in such a way as
to minimize their contact with water.
• Their polar hydrophilic carboxylate groups, on the
other hand, tend to remain in contact with the
surrounding water molecules.
• Driven by these two forces, soap molecules
spontaneously cluster into micelles.
26-10
Soaps and Detergents
• A soap micelle: nonpolar (hydrophobic) hydrocarbon
chains cluster in the inside and polar (hydrophilic)
carboxylate groups lie on the surface.
26-11
Soaps and Detergents
• micelle: A spherical arrangement of organic molecules
in water clustered so that their hydrophobic parts are
buried inside the sphere and their hydrophilic parts are
on the surface of the sphere and in contact with water.
• when soap is mixed with water-insoluble grease, oil,
and fats, the nonpolar parts of the soap micelles
“dissolve” these nonpolar dirt molecules and they are
carried away in the polar wash water.
26-12
Soaps and Detergents
 Soaps
form water-insoluble salts when used in
water containing Ca(II), Mg(II), and Fe(III) ions
(hard water).
-
2 CH3 ( CH2 ) 1 4 COO Na
+
+
Ca
2+
A s odiu m s oap
(sol u bl e i n wate r as m ice ll es )
2+
+ 2 N a+
[ CH3 ( CH2 ) 1 4 COO ] 2 Ca
C al ci u m s al t of a fatty acid
(in s olu ble in w ate r)
26-13
Synthetic Detergents
 The
design criteria for a good detergent are:
• a long hydrocarbon tail of 12 to 20 carbons.
• a polar head group that does not form insoluble salts
with Ca(II), Mg(II), or Fe(III) ions.
 The
most widely used synthetic detergents are
the linear alkylbenzenesulfonates (LAS).
26-14
Synthetic Detergents
1 . H2 SO 4
2 . Na OH
CH 3 ( CH2 ) 1 0 CH 2
Dodecylbe n z e n e
CH 3 ( CH2 ) 1 0 CH 2
SO 3
-
Na
+
S odiu m 4-dodecylbe n z en e s u lfon ate
(an an i on ic de te rge nt)
 Also
added to detergent preparations are:
• foam stabilizers.
• bleaches.
• optical brighteners.
26-15
Prostaglandins
 Prostaglandins:
A family of compounds that have
the 20-carbon skeleton of prostanoic acid.
9
5
7
6
8
1
3
2
4
COOH
10
11
12
13
14
15
16
18
17
19
20
Pros tan oi c aci d
26-16
Prostaglandins, origin
 Prostaglandins
are not stored in tissues as such,
but are synthesized from membrane-bound 20carbon polyunsaturated fatty acids in response
to specific physiological triggers.
• One such polyunsaturated fatty acid is arachidonic
acid (notice the all cis configurations).
9
8
11 12
6
14
5
COOH
15
Arach i don i c aci d
26-17
Prostaglandins, examples
• Among the prostaglandins synthesized biochemically
from arachidonic acid are:
O
9
COOH
PGE2
11
15
HO
HO H
HO
9
PGF2
COOH
11
15
HO
HO H
PGE2 generated in macrophages of the liver and lungs
triggers the earliest phase of fever following any infection
26-18
Prostaglandins
 Research
on the involvement of PGs in
reproductive physiology has produced several
clinically useful derivatives.
• (15S)-15-methyl-PGF2 is used as a therapeutic
abortifacient.
extra methyl group
at carb on -15
HO
9
COOH
11
HO
15
HO CH3
(15S)-15-Methyl-PGF2
26-19
Prostaglandins
• The PGE1 analog, misoprostol, is used to prevent the
ulceration associated with the use of aspirin.
O
COOH
PGE1
15
HO
16
HO H
O
COOCH 3
Mi s oprostol
HO
HO
15
CH3
16
26-20
Eicosanoids
 The
prostaglandins are members of an even
larger family of compounds called eicosanoids,
all of which contain 20 carbons and are derived
from polyunsaturated fatty acids.
1
5
HOOC
9
6
8
COOH
O
11
O
O
1
15
12
13
14
OH
Th romboxane A2
(a potent vasoconstrictor)
20
H
7
9 8
H
14
20
15
11
13
OH
OH
Prostacyclin
(a p latelet aggregation inhib itor)
26-21
Eicosanoids
 Leukotrienes
are found primarily in white blood
cells.
• One function is constriction of smooth muscles,
especially those of the lungs.
HO
11
9
1
7
20
6
COOH
5
S
O
COOH
glycin e
14
L-cys te i n e
Le u k otrie n e 4C(LTC4)
(a sm ooth m u scl e con s tri ctor)
N
H
HN
COOH
N H2
L-gl u tam ic acid
O
26-22
Steroids
 Steroids:
A group of plant and animal lipids that
have this tetracyclic ring structure.
C
A
D
B
 The
features common to the ring system of most
naturally occurring steroids are illustrated next.
26-23
Steroids
• The fusion of rings is trans and each atom or group at
a ring junction is axial.
• The pattern of atoms or groups along the ring
junctions is nearly always trans-anti-trans-anti-trans.
• The steroid system is nearly flat and quite rigid.
• Most have have axial methyl groups at C-10 and C-13.
CH3
H
H
CH3
H
H
26-24
Cholesterol
H3 C
H3 C
H
H
H
HO
26-25
Androgens
 Androgens
- male sex hormones.
H3 C
H3 C
OH
H
H
H
H3 C
H3 C
H
O
O
H
H
H
HO
Te stoste ron e
An dros teron e
26-26
Synthetic Anabolic Steroids
• A way to increase the testosterone concentration is to
use a prohormone, which the body converts to
testosterone; for example “andro”.
H3 CHO CH3
H3 C
H
O
Meth androstenolon e
H
H3 C
H3 C
H
N and rolon e decan oate
H
Meth enolone
O
OC(CH2 ) 8 CH3
CH3
H
H
O
H
H
O
OH
H
CH3
H
H3 C
O
H3 C
H
H
O
H3 C
H
4-An dros tene-3,17-dione
(an dro)
26-27
Available on the internet, dangerous


Generic Name: methandrostenolone
Danabol / Dianabol has always been one of the most popular anabolic
steroids available. Danabol / Dianabol's popularity stems from it's almost
immediate and very strong anabolic effects. 4-5 tablets a day is enough to
give almost anybody dramatic results. It is usually stacked with deca
durabolin and testosterone enanthate. Along with strong anabolic effects
comes the usual androgen side effects, users often report an overall sense
of well being. Danabol / Dianabol is a strong anabolic and androgenic
product. It most often produced dramatic gains in size and strength. Danabol
/ Dianabol was also shown to increase endurance and glycogen retention.
The down side is that this drug is responsible for a number of side effects. It
is an alpha alkylated 17 compound, which is quite toxic to the liver. Average
dosages for Danabol / Dianabol have been in the range of 15mg to 30mg a
day oral or 50mg to 100mg a week by injection. Regarded by many athletes
as being one of the most effective oral steroids ever produced. It was not
known as the "Breakfast of Champions" for nothing. Danabol / Dianabol is
still one of the most effective strength and size building oral steroids
probably second only to Anadrol 50 but it is not as harsh on the system as
Anadrol 50 is.
26-28
Estrogens
 Estrogens
- female sex hormones.
CH3
H3 C
H3 C
C= O
H
O
H3 C
H
H
H
H
H
O
H
HO
Proge s te ron e
H3 C
H3 C
Estrone
OH
H
H
H
H3 C
H3 C
H
O
O
H
H
H
HO
Te stoste ron e
An dros teron e
26-29
Synthetic Estrogens
 Progesterone-like
analogs are used in oral
contraceptives.
"Nor" re fers to th e abs e n ce
of a me th yl grou p h ere .
Th e me th yl grou p is pre se n t
i n e th i n dron e
HO
C CH
H3 C
H
H
H
H
O
Noreth in dron e
26-30
Glucorticoid Hormones
•
•
•
•
Synthesized in the adrenal cortex.
Regulate metabolism of carbohydrates.
Decrease inflammation.
Involved in the reaction to stress.
CH2 OH
H3 C
O
H3 C
C= O
OH
H
H
O
CH2 OH
H3 C
HO
H3 C
H
C= O
OH
H
H
H
O
C orti son e
C orti sol
26-31
Mineralocorticoid Hormones
• Synthesized in the adrenal cortex.
• Regulate blood pressure and volume by stimulating
the kidneys to absorb Na+, Cl-, and HCO3-.
OH
O
H3 C
CH
CH2 OH
C=O
H
H
H
O
Al dos te rone
26-32
Bile Acids
 Synthesized
in the liver, stored in the gallbladder,
and secreted into the intestine where their
function is emulsify dietary fats and aid in their
absorption and digestion.
OH
COOH
H
H
HO
H
H
OH
26-33
Biosynthesis of Steroids
 The
building block from which all carbon atoms
of steroids are derived is the two carbon acetyl
group of acetyl-CoA
Stage 1: synthesis of isopentenyl pyrophosphate from
three molecules of acetyl-CoA.
Stage 2: synthesis of cholesterol.
Stage 3: conversion of cholesterol to other steroids.
bil e acids (e .g., chol ic acid)
chol e ste rol
s ex hormone s (e.g., te s tos te rone and es trone )
mi ne ral ocorti coi d horm one s (e.g., aldoste rone )
glucocorti coi d hormones (e .g., cortis one )
26-34
Vitamin E
OH
Fou r is opre n e u n i ts , joi n e d
h e ad-to-tai l, be gin n i n g h ere
an d e n din g at th e aromatic ri n g
O
Vi tami n E (-Tocoph e rol)
26-35
Phospholipids
 Phospholipids
are the second most abundant
group of naturally occurring lipids.
• They are found almost exclusively in plant and animal
membranes, which typically consist of 40% -50%
phospholipids and 50% - 60% proteins.
• The most abundant phospholipids are esters of
phosphatidic acid (glycerol esterified with two
molecules of fatty acid and one of phosphoric acid).
• The three most abundant fatty acids in phosphatidic
acids are palmitic acid (16:0), stearic acid (18:0), and
oleic acid (18:1).
26-36
Phosphatidic acids, an example
A
phosphatidic acid
• Further esterification with a low-molecular weight
alcohol gives a phospholipid.
26-37
Phospholipids
• Among the most common of these low-molecularweight alcohols are:
26-38
Phospholipids, an example
A
lecithin
In aqueous solution, phospholipids spontaneously
form into a lipid bilayer, with a back-to-back
arrangement of lipid monolayers.
26-39
Biological Membranes
 Fluid
mosaic model: A biological membrane
consists of a phospholipid bilayer with proteins,
carbohydrates, and other lipids embedded on the
surface and in the bilayer.
• fluid: Signifies that the protein components of
membranes “float” in the bilayer and can move freely
along the plane of the membrane.
• mosaic: Signifies that the various components of the
membrane exist side by side, as discrete units rather
than combining to form new molecules and ions.
26-40
Biological Membranes
• Fluid-mosaic model of a biological membrane showing
the lipid bilayer and membrane proteins on the inner
and outer surfaces of the membrane and penetrating
the thickness of the membrane.
26-41
Fat-Soluble Vitamins
 Vitamins
are divided into two broad classes on
the basis of their solubility:
• Those that are fat soluble, and hence classified as
lipids.
• Those that are water soluble.
 The
fat-soluble vitamins include A, D, E, and K.
26-42
Vitamin A
• Occurs only in the animal world.
• Found in the plant world in the form of a provitamin in
a group of pigments called carotenes.
26-43
Vitamin A
 The
best understood role of Vitamin A is its
participation in the visual cycle in rod cells.
• the active molecule is retinal (vitamin A aldehyde),
which forms an imine with an -NH2 group of the protein
opsin to form the visual pigment called rhodopsin.
• the primary chemical event of vision in rod cells is
absorption of light by rhodopsin followed by
isomerization of the 11-cis double bond to the 11-trans
configuration.
26-44
Vitamin A and the Chemistry of Vision
26-45
Vitamin D
A
group of structurally related compounds that
play a role in the regulation of calcium and
phosphorus metabolism.
• The most abundant form in the circulatory system is
vitamin D3.
26-47
Vitamin E
 Vitamin
E is a group of compounds of similar
structure, the most active of which is tocopherol.
• In the body, vitamin E functions as an antioxidant; it
traps peroxy radicals of the type HOO• and ROO•
formed as a result of oxidation by O2 of unsaturated
hydrocarbon chains in membrane phospholipids.
26-48
Vitamin K
 The
name of this vitamin comes from the German
word Koagulation, signifying its important role in
the blood-clotting process.
26-49