Complex Lipids: Glycerophospholipids and Sphingolipids

 
Lipids
 
Bioc. 201
 
بسم الله الرحمن الرحيم
 
1
 
Complex Lipids:
Glycerophospholipids
 
2
 
Glycerophospholipids
 
Glycerophospholipids are similar
in structure to triglycerides
except that they only have 
two
esterified fatty acids. The third
position on the glycerol
backbone instead contains a
phospholipid head group
.
The two fatty acids in
phospholipids are normally 14
to 24 carbon atoms long, with
one fatty acid commonly
saturated and the other
unsaturated.
 
3
 
Glycerophospholipids
 
There are several types of phospholipid head groups, such as:
choline, inositol, serine, and ethanolamine, which are all
hydrophilic in nature.
The various types of glycerophospholipids are named based on
the type of phospholipid head group present, e.g.
phosphatidylcholine.
 
4
 
Glycerophospholipids
 
Because glycerophospholipids contain both hydrophobic fatty acid
C―H chains and a hydrophilic head group, they are by definition
amphipathic lipid molecules 
and, as such, are found on the surface
of lipid layers.
The polar hydrophilic head group faces outward the aqueous
environment, whereas the fatty acid chains face inward away from
the water in a perpendicular orientation with respect to the lipid
surface.
 
5
 
Complex Lipids:
Sphingolipids
(Sphingomyelin, Cerebrosides and Gangliosides)
 
6
 
Sphingolipids
 
Shingolipids
 are typically found in brain
tissues.
Sphingolipids are derivatives of the C18
amino alcohols  
sphingosine
,
dihydrosphingosine
, and their C16, C17,
C19, and C20 homologs.
Sphingosine is rare in plants and animals
while  sphingolipids are common.
 
7
 
Sphingolipids
 
8
 
Sphingolipids
 
Simplest sphingolipids are 
ceramides.
    
Sphingosine + N-linked fatty acid = ceramide
Ceramides occur only in small amounts in
plant and animal tissues but form the parent
compounds of more abundant sphingolipids:
1.
Sphingomyelins.
2.
Cerebrosides.
3.
Gangliosides.
 
9
 
Sphingolipids: 1. Sphingomyelin
 
Sphingomyelin
 the only
significant sphingophospholipid in
humans.
The backbone of sphingomyelin is
the amino alcohol sphingosine,
rather than glycerol.
A long-chain fatty acid is attached
to the amino group of
sphingosine through an 
amide
linkage
, producing a 
ceramide
,
which can also serve as a
precursor of glycolipids.
 
10
 
 
Sphingolipids: 1. Sphingomyelin
 
The alcohol group at 
carbon
1
 of sphingosine is
esterified to
phosphorylcholine,
producing sphingomyelin.
They can also be classified
as 
sphingophposholipids
.
 
Sphingomyelin is an
important constituent of
the myelin of nerve fibers.
 
11
 
Sphingolipids: 2. Cerebrosides
 
Cerebrosides,
 the simplest sphingoglycolipids (alternatively
glycosphingolipids), are ceramides with head groups that
consist of a single sugar residue.
The carbohydrates are most often 
glucose
 or 
galactose
.
Cerebrosides, in contrast to phospholipids, 
lack phosphate
groups
 and hence are most frequently 
nonionic 
compounds.
 
 
12
 
Sphingolipids: 2. Cerebrosides
 
Galactocerebrosides:
Most prevalent in the
neuronal cell membranes
of the brain.
have a 
β
-D-galactose 
head
group.
 
13
 
Sphingolipids: 2. Cerebrosides
 
Glucocerebrosides:
They occur mostly in non-neuronal tissues.
have a 
β
-D-glucose 
head group.
 
14
 
 
Sphingolipids: 3. Gangliosides
 
Gangliosides form the most complex group of
sphingolipids.
They are ceramide oligosaccharides that include
among their sugar groups 
at least one sialic acid
residue.
Gangliosides are primarily components of cell
surface membranes and constitute a significant
fraction of brain lipids. Other tissues also contain
gangliosides but in lesser amount.
 
15
 
Sphingolipids: 3. Gangliosides
 
16
 
Sphingolipids: 3. Gangliosides
 
Glycosphingolipids are the determinants of
blood types.
 
17
 
* The symbol Fuc represents the sugar fucose.
 
Waxes
 
18
 
Waxes
 
Waxes are typically
esters of fatty acids and
fatty alcohols.
They protect the skin of
plants and fur of
animal.
Natural protective layer
in fruits and vegetables.
 
19
 
 
Waxes
 
20
 
Weakly polar head
group with saturated
fatty acid and
unsaturated fatty
alcohol (typically).
 
Steroids:
Cholesterol and Bile Acids
 
21
 
Steroids
 
Another major class of lipids is steroids, which have
structures totally different from the other classes of lipids.
 
The main feature of steroids
is the 
ring system 
of 
three
cyclohexanes
 and 
one
cyclopentane 
in a fused ring
system.
 There are a variety of
functional groups that may
be attached. The main
feature, as in all lipids, is the
large number of carbon-
hydrogens which make
steroids non-polar.
 
22
 
Steroids
 
Steroids include such well known compounds
as:
Cholesterol
Male & female sex hormones
Bile acids
Vitamin D
Adrenal corticosteroids
 
23
 
Cholesterol
 
Cholesterol is an unsaturated steroid
alcohol.
It consists of 
four fused hydrocarbon
rings
 (A, B, C, and D) called the “steroid
nucleus”), and it has an 
eight-carbon,
branched hydrocarbon chain
 attached to
carbon 17 of the D ring. Ring A has a
hydroxyl group at carbon 3, and ring B
has a double bond between carbon 5 and
carbon 6
Cholesterol is a very hydrophobic
compound. The only hydrophilic part of
cholesterol is the hydroxyl group in the A-
ring. It is, therefore, also an amphipathic
lipid and is found on the surface of lipid
layer along with phospholipids.
 
24
 
Cholesterol
 
Cholesterol can also exist in an
esterified form called 
cholesterol ester
,
with the hydroxyl group conjugated by
an ester bond to a fatty acid, in the
same way as in triglycerides.
In contrast to free cholesterol, there
are 
no polar 
groups on cholesterol
esters, making them very 
hydrophobic
.
Because it is not charged, cholesterol
ester are classified as a neutral lipid
and are not found on the surface of
lipids layers but instead are located in
the center of lipid drops and
lipoproteins, along with triglycerides.
 
25
 
Cholesterol
 
Cholesterol is almost exclusively synthesized by animals, but plants
do contain other sterols similar in structure to cholesterol.
Cholesterol is also unique in that, unlike other lipids, it is not readily
catabolized by most cells and, therefore, does not serve as a source
of fuel.
Cholesterol performs a number of essential functions in the body.
For example:
Cholesterol is a structural component of all cell membranes,
modulating their fluidity.
In specialized tissues, cholesterol is a precursor of bile acids, steroid
hormones, and vitamin D. It is therefore of critical importance that
the cells of the body be assured an appropriate supply of
cholesterol.
 
26
 
Synthesis of Cholesterol
 
Occurs in cytosol.
Requires NADPH, ATP, and O
2
.
Highly regulated.
80 % in liver, ~10% intestine, ~5% skin.
The overall equation:
 
27
 
Synthesis of Cholesterol
 
Cholesterol is synthesized
by virtually all tissues in
humans, although liver,
intestine, adrenal cortex,
and reproductive tissues,
including ovaries, testes,
and placenta, make the
largest contributions to the
body’s cholesterol pool.
 
28
 
Cholesterol
 
The liver plays a central role
in the regulation of the
body’s cholesterol
homeostasis. For example,
cholesterol enters the liver’s
cholesterol pool from a
number of sources including
dietary cholesterol
, as well
as cholesterol synthesized
de novo by extrahepatic
tissues 
and 
by the liver
itself.
 
29
 
Synthesis of Cholesterol
 
30
 
The key step in the biosynthesis of cholesterol is the conversion of
3-hydroxy-3-methyl-glutaryl-Coenzyme A
 to 
mevalonate
 by 
HMG
CoA reductase
. This is the 
rate limiting step 
in cholesterol
biosynthesis.
 
Synthesis of Cholesterol
 
31
 
Degradation of Cholesterol
 
The ring structure of
cholesterol cannot be
metabolized to CO2 and
H2O in humans.
Rather, the intact sterol
nucleus is eliminated from
the body by conversion to
bile acids 
and 
bile salts
,
which are excreted in the
feces, and by secretion of
cholesterol into the bile,
which transports it to the
intestine for elimination.
 
32
 
Degradation of Cholesterol
 
Some of the cholesterol in
the intestine is modified by
bacteria before excretion.
The primary compounds
made are the isomers
coprostanol
 and
cholestanol
, which are
reduced derivatives of
cholesterol. Together with
cholesterol, these
compounds make up the
bulk of neutral fecal sterols.
 
33
 
Bile Acids and Bile Salts
 
Bile consists of a watery mixture of organic and
inorganic compounds.
Phosphatidylcholine and bile salts (conjugated
bile acids) are quantitatively the most important
organic components of bile.
Bile can either pass directly from the liver where
it is synthesized into the duodenum through the
common bile duct, or be stored in the gallbladder
when not immediately needed for digestion.
 
34
 
Structure of Bile Acids
 
The bile acids contain 24 carbons, with
two or three hydroxyl groups and a side
chain that terminates in a carboxyl group.
The bile acids are 
amphipathic
 in that the
hydroxyl groups are α in orientation (they
lie “below” the plane of the rings) and the
methyl groups are β (they lie “above” the
plane of the rings). Therefore, the
molecules have both a polar and a
nonpolar face, and can act as 
emulsifying
agents
 in the intestine, helping prepare
dietary triacylglycerol and other complex
lipids for degradation by pancreatic
digestive enzymes.
 
35
 
Synthesis of Bile Acids
 
Bile acids are synthesized
in the liver by a multistep,
multiorganelle pathway
The most common
resulting compounds,
cholic acid (a triol) and
chenodeoxycholic acid (a
diol), are called “primary”
bile acids.
 
36
 
Synthesis of Bile Salts
 
Before the bile acids leave the
liver, they are conjugated to a
molecule of either 
glycine
 or
taurine
 by an 
amide bond
between the carboxyl group of
the bile acid and the amino
group of the added compound.
These new structures include
glycocholic and glycocheno-
deoxycholic acids, and
taurocholic and taurocheno-
deoxycholic acids
 
37
 
Lipoproteins
 
38
 
Plasma Lipoproteins
 
The plasma lipoproteins are
spherical
 macromolecular
complexes of 
lipids
 and specific
proteins 
(apolipoproteins or
apoproteins).
Lipoproteins function:
The main role is the delivery of fuel
to peripheral cells.
to provide an efficient mechanism
for transporting their lipid contents
to (and from) the tissues.
to keep their component lipids
soluble as they transport them in
the plasma.
 
39
 
Plasma Lipoproteins
 
The lipoprotein particles include:
chylomicrons (CM),
very-low-density lipoproteins (VLDL),
low-density lipoproteins (LDL),
high-density lipoproteins (HDL).
They differ in lipid and protein
composition, size (range from 10 to
1200 nm), density, and site of origin.
[Note: Although cholesterol and its
esters are shown as one component in
the center of each particle, physically
cholesterol is a surface component
whereas cholesteryl esters are located
in the interior of the lipoproteins.]
 
40
 
 
Apolipoproteins
 
Apolipoprotein are primarily located on the 
surface
 of
lipoprotein particles.
Apolipoproteins are divided by 
structure
 and 
function 
into
five major classes
, A, B, C, D, and E, with most classes
having 
subclasses
. For example, apolipoprotein (or apo) A-I
and apo C-II.
Functions:
providing recognition sites for cell-surface receptors
they help maintain the structural integrity of lipoproteins
serving as activators or coenzymes for enzymes involved in
lipoprotein metabolism.
[Note: Functions of all of the apolipoproteins are not yet
known.]
 
41
 
Composition of plasma lipoproteins
 
Lipoproteins are composed of 
a
neutral lipid core 
(containing
triacylglycerol and cholesteryl esters)
surrounded by a 
shell of amphipathic
apolipoproteins, phospholipid, and
non-esterified (free) cholesterol.
These amphipathic compounds are
oriented so that their polar portions
are exposed on the surface of the
lipoprotein, thus making the particle
soluble in aqueous solution.
The triacylglycerol and cholesterol
carried by the lipoproteins are
obtained either from the diet
(exogenous source) or from de novo
synthesis (endogenous source).
 
42
 
Size and density of lipoprotein
particles
 
Chylomicrons are the lipoprotein
particles lowest in density and
largest in size, and contain the
highest percentage of lipid and the
lowest percentage of protein.
VLDLs and LDLs are successively
denser, having higher ratios of
protein to lipid.
HDL particles are the densest.
 
43
 
Chylomicrons
 
Chylomicrons are the largest and
least dense of the lipoproteins.
These 1000-nanometer particles
originate in the intestinal mucosa.
 Their function is to transport
dietary triglycerides and
cholesterol absorbed by the
intestinal epithelial cells.
Chylomicrons contain about 1-2%
protein, 85-88% triglycerides,
~8% phospholipids, ~3%
cholesteryl esters and ~1%
cholesterol.
 
44
 
very-low-density lipoproteins (VLDL)
 
Very low density lipoproteins are
approximately 25-90
nanometers in size.
produced primarily by the liver
with lesser amounts contributed
by the intestine
VLDL contains 5-12% protein,
50-55% triglycerides, 18-20%
phospholipids, 12-15%
cholesteryl esters and 8-10%
cholesterol.
leaves a residue of cholesterol in
the tissues during the process of
conversion to LDL.
 
45
 
low-density lipoproteins (LDL)
 
Low density lipoproteins (bad
cholesterol) are smaller than VLDL,
approximately 26 nanometers.
LDL contains 20-22% protein, 10-15%
triglycerides, 20-28% phospholipids,
37-48% cholesteryl esters, and 8-10%
cholesterol.
LDL is produced by the liver.
LDL and HDL transport both dietary
and endogenous cholesterol in the
plasma, but LDL is the main
transporter of cholesterol and
cholesteryl esters and makes up more
than half of the total lipoprotein in
plasma.
 
46
 
high-density lipoproteins (HDL)
 
High density lipoproteins (good cholesterol)
are the smallest of the lipoproteins. HDL
particles have a size of 6-12.5 nanometers.
HDL contains approximately 55% protein, 3-
15% triglycerides, 26-46% phospholipids, 15-
30% cholesteryl esters, and 2-10%
cholesterol.
HDL is produced in the liver and intestine .
HDL contains a large number of different
proteins including apolipoproteins such as
apo-AI (apolipoprotein A1), apo-CI, apo-CII,
apo-D, and apo-E.
The HDL proteins serve in lipid metabolism,
complement regulation, and participate as
proteinase inhibitors and acute phase
response to support the immune system
against inflammation and parasitic diseases.
 
47
 
LDL 
vs
 HDL
 
 
48
 
Plasma Lipoproteins
 
In humans, the transport
system is less perfect than
in other animals and, as a
result, humans experience a
gradual deposition of lipid—
especially cholesterol—in
tissues. This is a potentially
life-threatening occurrence
when the lipid deposition
contributes to plaque
formation, causing the
narrowing of blood vessels
(atherosclerosis).
 
49
 
Biological Membranes
 
50
 
Biological Membranes
 
Biological membranes are
thin, fluid structures that
form the boundary
between the exterior and
interior of the cell, as well
as between different
cellular compartments.
Biological membranes are
made of three major
components: 
lipids
,
proteins
, and 
sugars
.
 
51
 
Fluid Mosaic Membrane Model
 
Membrane structure according to
the famous “
fluid mosaic
membrane model
” of Singer and
Nicolson is described as a sea of
lipids with protein icebergs.
Nowadays, it has been believed
that biological membranes are
crowded and much more complex
dynamic systems, consisting of
lipids assembled into patches that
have different protein
composition than the surrounding
membrane. These patches can
vary in thickness and fluidity.
 
52
 
History of Fluid Mosaic Model
 
53
 
Functions of Biological Membranes
 
Form cell’s boundary.
Control the selective transport of substances in and out of
cells (transport of nutrients and keep out unwanted molecules
and toxic material).
Allow passage of water
Maintain intracellular pH, ionic concentration
Hold the cells together by cell: cell interactions.
Role in cell recognition and adhesion.
Control the signaling and the communication between cells.
provide a unique environment for protein-protein and
protein-lipid interactions.
 
54
 
Structure of Biological Membranes
 
All biomembranes of eukaryotes and eubacteria have a
common general structure, in which two-layered sheets of
lipid molecules have protein embedded in them
(Archebacteria have membranes that are monolayers but look
and behave like bilayers).
Non-covalent interactions are between lipids: lipids, lipids:
proteins and proteins: proteins
Sugars are attached by covalent bonds to some of the lipid
and protein molecules. They are found on one side of the
membrane only (carbohydrate moieties are always outside
the cell).
Specific function of each membrane depends on the
membrane proteins that are present in that membrane.
 
55
 
Lipid Bilayer
 
Membrane lipids are 
amphipathic
molecules consisting of a hydrophilic
section (the polar head) and a
hydrophobic section (the
hydrocarbon tail).
They 
self-assemble 
into a bilayer
structure in an aqueous environment
where the hydrophobic tails point
towards the interior facing each
other, while the hydrophilic head
groups face the aqueous exterior on
each side of the bilayer. 
By this way,
the contact between the tails and
water is minimized.
The thickness of lipid bilayers is
typically about 5-10 nm.
 
56
 
Lipid Bilayer
 
57
 
The major classes of lipids present in biological membrane
are:
1.
Fatty Acids.
2.
Glycerophospholipids (the most abundant class of lipid
molecules found in cell membranes).
3.
Sphingolipids (the second major class of lipid found in cell
membranes).
4.
Sterols (cholesterol).
The other lipids are:
5. Galactolipids and Sulpholipids present specifically in thylakoid
membranes in chloroplasts.
6. Glycerol Dialkyl Tetra Ether lipids present only in
Archaebacteria.
 
Lipid Bilayer
 
58
 
Membrane Proteins
 
59
 
Although the basic structure of biological membranes
is provided by the lipid bilayer, membrane proteins
perform most of their specific functions.
Proteins give each type of membrane in the cell its
characteristic functional properties.
Because lipid molecules are small compared with
protein molecules, there are always many more lipid
molecules than protein molecules in membranes.
The outer membrane of a cell, the plasma membrane,
typically consists of about 50 lipid molecules for each
protein molecule in a membrane that is 50% protein by
mass (w/w; molar ratio of ~50:1).
 
Protein:Lipid Ratio
 
Protein:lipid ratio in the membrane depends
on the function.
Pure lipid: insulation (neuronal cells).
Myelin (Schwann cell) membrane has 18%
protein (phospholipids are great insulators).
Mitochondrial membrane is 76% protein (has
many transporters and enzymes)
 
60
 
Membrane Proteins
 
Membrane proteins can be divided into two types:
Integral membrane proteins.
Peripheral membrane proteins.
 
61
 
Integral Membrane Proteins
 
Integral membrane proteins:
insoluble in water.
permanently 
embedded in lipid
bilayers.
portions
 of these proteins are in
van der Waals
 contact with the
hydrophobic region
 of the
membrane.
Integral membrane proteins may
be 
exposed
 either to the 
exterior
surface of the membrane or to
the 
interior 
compartment, or they
may 
span 
(cross)
 
the bilayer
completely.
 
62
 
Peripheral Membrane Proteins
 
Peripheral membrane
proteins:
usually water soluble.
adhere temporarily to the
lipid bilayer or to integral
membrane proteins by
various interactions (weakly
bound) such as
hydrophobic, electrostatic
and other types of non-
covalent interactions.
may be attached to either
the interior or exterior
surface of the bilayer.
 
63
 
Pore- and Channel- Forming Proteins
and Peptides
 
Most integral proteins are
transmembrane proteins which go from
one side of a membrane through to the
other side of the membrane, function
as gateways to deny or permit the
transport of specific substances across
the hydrophobic barrier of cellular
membrane to get into the cell or out of
the cell as in the case of waste
byproducts.
Pore-forming molecules are ranging
from small 
peptides
 that can self-
assemble to pores with weak selectivity
for specific ions to large
transmembrane 
proteins
 that regulate
the passage of small charged molecules.
 
64
 
Micelles, Bilayers and Liposomes
 
An inherent property of the
lipid molecules is to expel
water and close upon itself.
When salts of fatty acids or
soap molecules or
phospholipids are added
drop wise to aqueous
medium (water), they form
monolayers initially, as the
hydrophilic head interacts
with water at the air -water
interface and the
hydrophobic tail faces
outwards to the air.
 
65
 
Micelles
 
In aqueous solution (water),
amphiphilic molecules, such as
soaps and detergents, 
can
form 
monolayers
 on the air-
water interface and can also
form 
micelles
.
Fatty acids (one tail).
max 20 nm.
the hydrophilic heads interact
with the aqueous medium and
the tails with each other with
some aqueous solution
trapped inside the micelles
which are thermodynamically
stable.
 
66
 
Bilayers
 
Soap bubbles are the
bilayers of soap molecules.
The hydrophobic tails 
of
the soap molecules are
packed beside one another
and point into the
hydrophobic air. 
The
hydrophilic heads
 of the
soap molecules surround a
thin shell of water that
packed in the center of the
bilayer.
 
67
 
Bilayers
 
Unlike soap bilayers,
l
ipid bilayers are
oriented with their
hydrophobic tails inside
the bilayers
 w
hile the
hydrophilic heads are in
contact with  the
aqueous solution on
each side.
Charged polar head
group of two layers
p
rovides both  surfaces
with an 
ionic coat
.
 
68
 
Liposomes
 
A
 suspension of
phospholipid in water
forms multilamellar
vesicles that have an
onion-like arrangement
of lipid bilayer.
Phospholipids bilayers
that
 e
nclose an
aqueous compartment
 
69
 
Hormones
 
70
 
Hormones
 
Hormones
 are 
chemical signals 
that are secreted into
the circulatory system and communicate regulatory
messages within the body.
secrete by 
endocrine glands.
reach all parts of the body, but only 
target cells 
are
equipped to respond.
recognized by the presence of 
hormone receptors 
on:
The outside of the plasma membrane or
In the cytoplasm.
 
71
 
Endocrine System
 
72
 
Endocrine glands
 
is a structure whose
primary function is to secrete hormones.
Endocrine Organs:
1.
Purely endocrine organs:
Pituitary gland
Pineal gland
Thyroid gland
Parathyroid glands
Adrenal glands
 (
Cortex and Medulla ).
2.
Endocrine cells in other organs
Pancreas
Thymus
Gonads
Hypothalamus
 
Hormones
 
There are two main types of hormones:
1.
Circulating hormones
2.
Local hormones
 
 
73
 
Circulating Hormones (Endocrines)
 
1. Circulating hormones (Endocrines):
Are hormones that diffuse into the blood and act
on distant target cells.
Most circulating hormones are synthesized and
secreted by specialized epithelial cells (endocrine)
located in structures called endocrine glands.
Some endocrine cells are not found in structures
limited to the production of hormones, For
example:
Enteroendocrine cells: 
are scattered among other
epithelial cells that line the digestive tract. They
secrete hormones involved in the digestive
process.
Neurohormones: 
secreted by neurons are called
neurohormones that are secreted by cells in the
hypothalamus.
 
74
 
Local Hormones
 
2. Local hormones:
Paracrines Hormones:
are chemical messengers that act on
nearby cells.
An example is 
histamine
 which is
released by Mast cells and damaged
tissue cells. It acts on nearby blood
vessels, causing them to dilate.
 
Autocrines Hormones:
are chemical messengers act on the
same cells that secreted them.
An example is interleukin-2 (IL-2).
 
75
 
How Hormones work?
 
The endocrine system secretes hormones that
coordinate 
slower
 but 
longer-acting
responses including reproduction,
development, energy metabolism, growth,
and behavior.
Hormones only influence cells that have
specific target receptors for that particular
hormone.
 
76
 
How Hormones work?
 
Mechanisms of hormone
release:
Humoral
:
 in response to
changing levels of ions or
nutrients in the blood.
Neural
:
 stimulation by
nerves.
Hormonal
: 
stimulation
received from other
hormones.
 
77
 
Chemistry of Hormones
 
There are four principal classes of hormones:
1.
Steroids.
2.
Biogenic amines.
3.
Eicosanoids.
4.
Peptides and proteins.
 
78
 
1. Steroid Hormones
 
They are all derived from 
cholesterol
.
synthesized by the adrenal cortex, the gonads, and the
placenta.
exert their effects in two ways:
They bind directly to membrane receptors.
As they are fat-soluble, they pass through cell membranes (by
diffusion) where they attach to receptors in the cytoplasm.
Being water-insoluble, they circulate in the blood bound to
plasma proteins.
There are several types of steroid hormones:
Corticoids.
Sex Steroids.
 
79
 
1. Steroid Hormones
 
80
 
1. Steroid Hormones: Corticoids
 
Glucocorticoids
 (
mainly
Cortisol
, and also 
cortisone
and 
corticosterone
) 
are
released by the adrenal
cortex in response to stress.
They increase the
breakdown of fats and
proteins into glucose to
stop inflammation (immune
defence).
Mineralocorticoids 
(e.g.
aldosterone) are also
produced by the adrenal
glands and reduce salt
secretion in the kidneys.
 
81
 
1. Steroid Hormones: 
Sex Steroids
 
These are released mainly by the ovaries
and testes but also by the adrenal
glands.
The ovaries secrete:
Estrogens: 
Estradiol is produced in large
amounts in females and has feminising
effects, promoting female secondary
sexual characteristics, water retention,
calcium metabolism, sexual behaviour
and maternal behaviours.
Progesterone
 prepares the uterus for
the implantation of a fertilised ovum and
regulates the stages of pregnancy.
 
 
82
 
1. Steroid Hormones: 
Sex Steroids
 
The testes secrete:
Androgens:
 Testosterone is
produced in large amounts in
males and has masculinising
and defeminising effects;
maintaining male secondary
sexual characteristics and
promoting aggressive and
sexual behaviours.
 
 
83
 
2. Biogenic Amines
 
Biogenic amines are 
small, water-soluble
compounds.
synthesized from 
amino acids 
and act as
neurotransmitters and hormones in animals.
Hormones of this chemical type include the:
1. Thyroid Hormones.
2. Catecholamines.
3. Histamine.
 
84
 
2. Biogenic Amines Functions
 
sources of nitrogen and precursors for the
synthesis of hormones, alkaloides, nucleic
acids, and proteins.
influence the processes in the organism such
as the regulation of body temperature,
increase or decrease of blood pressure.
Some biogenic amines contribute to the flavor
and taste of food.
 
85
 
2. Biogenic Amines: Thyroid Hormones
 
The thyroid hormones,
thyroxine (T4) 
and
triiodothyronine (T3),
are 
tyrosine-based
hormones
 produced by
the thyroid gland.
Thyroid hormones are
unique biological
molecules in that they
incorporate iodine in
their structure.
 
86
 
2. Biogenic Amines: Thyroid
Hormones Functions
 
Control proteins, fats,
and carbohydrates
metabolism (
metabolic
rate
).
Regulate heart rate,
energy level, body
temperature, 
fetal and
childhood growth, and
central nervous system
(CNS) 
development
.
Stimulate Na
+
-K
+
 pumps.
 
87
 
2. Biogenic Amines: Catecholamines
 
Catecholamines are synthesized in the brain, in
the adrenal medulla, and by some nerve fibres.
Catecholamines are released into the blood when
a person is under physical or emotional stress.
The main catecholamines are:
Dopamine.
Norepinephrine (Noradrenalin).
Epinephrine (Adrenalin).
 
88
 
2. Biogenic Amines: Catecholamines
 
 
89
 
2. Biogenic Amines: Catecholamines
Functions
 
Mediates a variety of the central nervous system
functions such as cognition, emotion, and memory
processing.
Dopamine
 helps control include behavior, mental
health, and voluntary movement.
Norepinephrine
 controls alertness, emotions, sleeping,
dreaming and learning. It is also responsible for
increasing the heart rate and blood flow to some parts
of the body such as the heart.
Adrenaline,
 the flight or fight response hormone, is
largely responsible for the immediate reactions in
response to stress.
 
90
 
2. Biogenic Amines: Histamine
 
Histamine is derived from the amino acid histidine.
Histamine produced by:
Mast cells (typically found in areas such as the nasal passages,
mouth, and blood vessels).
Basophil (a type of white blood cells).
Its biological effects are usually seen only when it is released in large
amounts in the course of allergic and other reactions.
 
 
91
 
2. Biogenic Amines: Histamine
Functions
 
The histamine reaction in relation to the immune
response (in both allergic reactions and immune
reactions) serves two main functions:
It causes vasodilation.
It induces fluid secretion at the site of infection.
Histamine plays a role in gastric secretion by
helping to induce the production of acid in the
stomach.
helps to regulate sleep.
 
92
 
3. Eicosanoids
 
Eicosanoids are derived
from the 20-carbon
fatty acid.
They are synthesized by
all cells of the body
The three major types
of eicosanoids are:
Prostaglandins.
Leukotrienes
Thromboxanes
 
 
93
 
3. Eicosanoids Functions
 
Thromboxane 
constricts blood vessels, supresses
cyclic AMP, and promotes platelet aggregation.
Leukotrienes
 are involved in several immune-
mediated inflammatory reactions.
Prostaglandins
 are known to dilate arterioles and
capillaries (control blood pressure), relax vascular
smooth muscle, open the bronchi of the lungs,
enhance blood flow through the kidneys, increase
urinary volume as well as the excretion of sodium
ions, and cause contraction of gut muscle in
humans.
 
94
 
References
 
Biochemistry
 
(Lippincott´s Illustrated Reviews series) 
by Champe P, Harvey
R, and Ferrier D.
Clinical Chemistry by Bishop M, Fody E and Schoeff L.
Biochemistry, by Voet D and Voet J.
 
95
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Complex lipids play crucial roles in cellular structure and function. Glycerophospholipids, such as phosphatidylcholine, are amphipathic molecules with hydrophobic fatty acid chains and hydrophilic head groups. They are key components of cell membranes. Sphingolipids, including sphingomyelin and ceramides, are found in brain tissues and are derivatives of sphingosine. These lipids contribute to cell signaling and integrity. Understanding the structures and functions of these complex lipids is essential in biological systems.

  • Complex lipids
  • Glycerophospholipids
  • Sphingolipids
  • Cell membranes
  • Biological systems

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  1. Lipids Bioc. 201 1

  2. Complex Lipids: Glycerophospholipids 2

  3. Glycerophospholipids Glycerophospholipids are similar in structure to triglycerides except that they only have two esterified fatty acids. The third position on backbone instead contains a phospholipid head group. The two fatty phospholipids are normally 14 to 24 carbon atoms long, with one fatty acid saturated and unsaturated. the glycerol acids in commonly the other 3

  4. Glycerophospholipids There are several types of phospholipid head groups, such as: choline, inositol, serine, and ethanolamine, which are all hydrophilic in nature. The various types of glycerophospholipids are named based on the type of phospholipid head group present, e.g. phosphatidylcholine. 4

  5. Glycerophospholipids Because glycerophospholipids contain both hydrophobic fatty acid C H chains and a hydrophilic head group, they are by definition amphipathic lipid molecules and, as such, are found on the surface of lipid layers. The polar hydrophilic head group faces outward the aqueous environment, whereas the fatty acid chains face inward away from the water in a perpendicular orientation with respect to the lipid surface. 5

  6. Complex Lipids: Sphingolipids (Sphingomyelin, Cerebrosides and Gangliosides) 6

  7. Sphingolipids Shingolipids are typically found in brain tissues. Sphingolipids are derivatives of the C18 amino alcohols dihydrosphingosine, and their C16, C17, C19, and C20 homologs. Sphingosine is rare in plants and animals while sphingolipids are common. sphingosine, 7

  8. Sphingolipids 8

  9. Sphingolipids Simplest sphingolipids are ceramides. Sphingosine + N-linked fatty acid = ceramide Ceramides occur only in small amounts in plant and animal tissues but form the parent compounds of more abundant sphingolipids: 1. Sphingomyelins. 2. Cerebrosides. 3. Gangliosides. 9

  10. Sphingolipids: 1. Sphingomyelin Sphingomyelin significant sphingophospholipid in humans. The backbone of sphingomyelin is the amino alcohol sphingosine, rather than glycerol. A long-chain fatty acid is attached to the amino sphingosine through an amide linkage, producing a ceramide, which can also serve as a precursor of glycolipids. the only group of 10

  11. Sphingolipids: 1. Sphingomyelin The alcohol group at carbon 1 of sphingosine esterified phosphorylcholine, producing sphingomyelin. They can also be classified as sphingophposholipids. Sphingomyelin important constituent of the myelin of nerve fibers. is to is an 11

  12. Sphingolipids: 2. Cerebrosides Cerebrosides, the simplest sphingoglycolipids (alternatively glycosphingolipids), are ceramides with head groups that consist of a single sugar residue. The carbohydrates are most often glucose or galactose. Cerebrosides, in contrast to phospholipids, lack phosphate groups and hence are most frequently nonionic compounds. 12

  13. Sphingolipids: 2. Cerebrosides Galactocerebrosides: Most prevalent in the neuronal cell membranes of the brain. have a -D-galactose head group. 13

  14. Sphingolipids: 2. Cerebrosides Glucocerebrosides: They occur mostly in non-neuronal tissues. have a -D-glucose head group. 14

  15. Sphingolipids: 3. Gangliosides Gangliosides form the most complex group of sphingolipids. They are ceramide oligosaccharides that include among their sugar groups at least one sialic acid residue. Gangliosides are primarily components of cell surface membranes and constitute a significant fraction of brain lipids. Other tissues also contain gangliosides but in lesser amount. 15

  16. Sphingolipids: 3. Gangliosides 16

  17. Sphingolipids: 3. Gangliosides Glycosphingolipids are the determinants of blood types. * The symbol Fuc represents the sugar fucose. 17

  18. Waxes 18

  19. Waxes Waxes esters of fatty acids and fatty alcohols. They protect the skin of plants and animal. Natural protective layer in fruits and vegetables. are typically fur of 19

  20. Waxes Weakly group with saturated fatty acid unsaturated alcohol (typically). polar head and fatty 20

  21. Steroids: Cholesterol and Bile Acids 21

  22. Steroids Another major class of lipids is steroids, which have structures totally different from the other classes of lipids. The main feature of steroids is the ring system of three cyclohexanes and one cyclopentane in a fused ring system. There are a variety of functional groups that may be attached. The main feature, as in all lipids, is the large number of carbon- hydrogens which make steroids non-polar. 22

  23. Steroids Steroids include such well known compounds as: Cholesterol Male & female sex hormones Bile acids Vitamin D Adrenal corticosteroids 23

  24. Cholesterol Cholesterol is an unsaturated steroid alcohol. It consists of four fused hydrocarbon rings (A, B, C, and D) called the steroid nucleus ), and it has an eight-carbon, branched hydrocarbon chain attached to carbon 17 of the D ring. Ring A has a hydroxyl group at carbon 3, and ring B has a double bond between carbon 5 and carbon 6 Cholesterol is a very hydrophobic compound. The only hydrophilic part of cholesterol is the hydroxyl group in the A- ring. It is, therefore, also an amphipathic lipid and is found on the surface of lipid layer along with phospholipids. 24

  25. Cholesterol Cholesterol can also exist in an esterified form called cholesterol ester, with the hydroxyl group conjugated by an ester bond to a fatty acid, in the same way as in triglycerides. In contrast to free cholesterol, there are no polar groups on cholesterol esters, making them very hydrophobic. Because it is not charged, cholesterol ester are classified as a neutral lipid and are not found on the surface of lipids layers but instead are located in the center of lipoproteins, along with triglycerides. lipid drops and 25

  26. Cholesterol Cholesterol is almost exclusively synthesized by animals, but plants do contain other sterols similar in structure to cholesterol. Cholesterol is also unique in that, unlike other lipids, it is not readily catabolized by most cells and, therefore, does not serve as a source of fuel. Cholesterol performs a number of essential functions in the body. For example: Cholesterol is a structural component of all cell membranes, modulating their fluidity. In specialized tissues, cholesterol is a precursor of bile acids, steroid hormones, and vitamin D. It is therefore of critical importance that the cells of the body be assured an appropriate supply of cholesterol. 26

  27. Synthesis of Cholesterol Occurs in cytosol. Requires NADPH, ATP, and O2. Highly regulated. 80 % in liver, ~10% intestine, ~5% skin. The overall equation: 27

  28. Synthesis of Cholesterol Cholesterol is synthesized by virtually all tissues in humans, although intestine, adrenal cortex, and reproductive tissues, including ovaries, testes, and placenta, make the largest contributions to the body s cholesterol pool. liver, 28

  29. Cholesterol The liver plays a central role in the regulation of the body s homeostasis. For example, cholesterol enters the liver s cholesterol pool from a number of sources including dietary cholesterol, as well as cholesterol synthesized de novo by extrahepatic tissues and by the liver itself. cholesterol 29

  30. Synthesis of Cholesterol The key step in the biosynthesis of cholesterol is the conversion of 3-hydroxy-3-methyl-glutaryl-Coenzyme A to mevalonate by HMG CoA reductase. This is the rate limiting step in cholesterol biosynthesis. 30

  31. Synthesis of Cholesterol 31

  32. Degradation of Cholesterol The cholesterol metabolized to CO2 and H2O in humans. Rather, the intact sterol nucleus is eliminated from the body by conversion to bile acids and bile salts, which are excreted in the feces, and by secretion of cholesterol into the bile, which transports it to the intestine for elimination. ring structure cannot of be 32

  33. Degradation of Cholesterol Some of the cholesterol in the intestine is modified by bacteria before excretion. The primary compounds made are the isomers coprostanol cholestanol, reduced derivatives cholesterol. Together with cholesterol, compounds make up the bulk of neutral fecal sterols. and are of which these 33

  34. Bile Acids and Bile Salts Bile consists of a watery mixture of organic and inorganic compounds. Phosphatidylcholine and bile salts (conjugated bile acids) are quantitatively the most important organic components of bile. Bile can either pass directly from the liver where it is synthesized into the duodenum through the common bile duct, or be stored in the gallbladder when not immediately needed for digestion. 34

  35. Structure of Bile Acids The bile acids contain 24 carbons, with two or three hydroxyl groups and a side chain that terminates in a carboxyl group. The bile acids are amphipathic in that the hydroxyl groups are in orientation (they lie below the plane of the rings) and the methyl groups are (they lie above the plane of the rings). Therefore, the molecules have both a polar and a nonpolar face, and can act as emulsifying agents in the intestine, helping prepare dietary triacylglycerol and other complex lipids for degradation by pancreatic digestive enzymes. 35

  36. Synthesis of Bile Acids Bile acids are synthesized in the liver by a multistep, multiorganelle pathway The most resulting cholic acid (a triol) and chenodeoxycholic acid (a diol), are called primary bile acids. common compounds, 36

  37. Synthesis of Bile Salts Before the bile acids leave the liver, they are conjugated to a molecule of either glycine or taurine by an amide bond between the carboxyl group of the bile acid and the amino group of the added compound. These new structures include glycocholic and glycocheno- deoxycholic taurocholic and taurocheno- deoxycholic acids acids, and 37

  38. Lipoproteins 38

  39. Plasma Lipoproteins The spherical complexes of lipids and specific proteins (apolipoproteins apoproteins). Lipoproteins function: The main role is the delivery of fuel to peripheral cells. to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. to keep their component lipids soluble as they transport them in the plasma. plasma lipoproteins macromolecular are or 39

  40. Plasma Lipoproteins The lipoprotein particles include: chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), high-density lipoproteins (HDL). They differ in lipid and protein composition, size (range from 10 to 1200 nm), density, and site of origin. [Note: Although cholesterol and its esters are shown as one component in the center of each particle, physically cholesterol is a surface component whereas cholesteryl esters are located in the interior of the lipoproteins.] 40

  41. Apolipoproteins Apolipoprotein are primarily located on the surface of lipoprotein particles. Apolipoproteins are divided by structure and function into five major classes, A, B, C, D, and E, with most classes having subclasses. For example, apolipoprotein (or apo) A-I and apo C-II. Functions: providing recognition sites for cell-surface receptors they help maintain the structural integrity of lipoproteins serving as activators or coenzymes for enzymes involved in lipoprotein metabolism. [Note: Functions of all of the apolipoproteins are not yet known.] 41

  42. Composition of plasma lipoproteins Lipoproteins are composed of a neutral lipid triacylglycerol and cholesteryl esters) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and non-esterified (free) cholesterol. These amphipathic compounds are oriented so that their polar portions are exposed on the surface of the lipoprotein, thus making the particle soluble in aqueous solution. The triacylglycerol and cholesterol carried by the lipoproteins are obtained either from the diet (exogenous source) or from de novo synthesis (endogenous source). core (containing 42

  43. Size and density of lipoprotein particles Chylomicrons are the lipoprotein particles lowest in density and largest in size, and contain the highest percentage of lipid and the lowest percentage of protein. VLDLs and LDLs are successively denser, having higher ratios of protein to lipid. HDL particles are the densest. 43

  44. Chylomicrons Chylomicrons are the largest and least dense of the lipoproteins. These 1000-nanometer particles originate in the intestinal mucosa. Their function is to transport dietary triglycerides cholesterol absorbed intestinal epithelial cells. Chylomicrons contain about 1-2% protein, 85-88% ~8% phospholipids, cholesteryl esters cholesterol. and the by triglycerides, ~3% ~1% and 44

  45. very-low-density lipoproteins (VLDL) Very low density lipoproteins are approximately nanometers in size. produced primarily by the liver with lesser amounts contributed by the intestine VLDL contains 5-12% protein, 50-55% triglycerides, phospholipids, cholesteryl esters and 8-10% cholesterol. leaves a residue of cholesterol in the tissues during the process of conversion to LDL. 25-90 18-20% 12-15% 45

  46. low-density lipoproteins (LDL) Low cholesterol) are smaller than VLDL, approximately 26 nanometers. LDL contains 20-22% protein, 10-15% triglycerides, 20-28% phospholipids, 37-48% cholesteryl esters, and 8-10% cholesterol. LDL is produced by the liver. LDL and HDL transport both dietary and endogenous cholesterol in the plasma, but LDL is the main transporter of cholesteryl esters and makes up more than half of the total lipoprotein in plasma. density lipoproteins (bad cholesterol and 46

  47. high-density lipoproteins (HDL) High density lipoproteins (good cholesterol) are the smallest of the lipoproteins. HDL particles have a size of 6-12.5 nanometers. HDL contains approximately 55% protein, 3- 15% triglycerides, 26-46% phospholipids, 15- 30% cholesteryl esters, cholesterol. HDL is produced in the liver and intestine . HDL contains a large number of different proteins including apolipoproteins such as apo-AI (apolipoprotein A1), apo-CI, apo-CII, apo-D, and apo-E. The HDL proteins serve in lipid metabolism, complement regulation, and participate as proteinase inhibitors response to support the immune system against inflammation and parasitic diseases. and 2-10% and acute phase 47

  48. LDL vs HDL 48

  49. Plasma Lipoproteins In humans, the transport system is less perfect than in other animals and, as a result, humans experience a gradual deposition of lipid especially tissues. This is a potentially life-threatening occurrence when the lipid deposition contributes formation, narrowing of blood vessels (atherosclerosis). cholesterol in to plaque the causing 49

  50. Biological Membranes 50

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