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LIPIDS part 2

Geromil J. Lara, RMT, MSMT

(2) GLYCERIDES
Phosphatidylcholine (Lecithin)
An amphipathic molecule
Similar to that of soap and detergent
molecules
Component of cell membranes
Major phospholipid in pulmonary
surfactant
Found in egg yolks and soybeans
As emulsifying agent in ice cream
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(2) GLYCERIDES
Phosphatidylethanolamine (Cephalin)
Similar in general structure to lecithin
Amine group bonded to the phosphoryl
group is the only difference

(3) NONGLYCERIDE LIPIDS


Sphingolipids
Are lipids that are not derived from glycerol
Amphipathic and structural components of
cellular membranes
Derived from sphingosine (long chain, Ncontaining alcohol)
Sphingomyelins
Glycosphingolipids

(3) NONGLYCERIDE LIPIDS


Sphingomyelins
Located throughout the body, but are
particularly important structural lipid
components of nerve cell membranes
Found in abundance in the myelin sheath
the surrounds and insulate cells of the CNS
Role is essential to proper cerebral
function and nerve transmission

(3) NONGLYCERIDE LIPIDS


Glycosphingolipids (Glycolipids)
Include the cerebrosides, sulfatides, and
gangliosides
Are built on a ceramide backbone structure,
which is a fatty acid amide derivative of
sphingosine

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(3) NONGLYCERIDE LIPIDS


Cerebrosides
Are characterized by the presence of a
single monosaccharide head group
Glucocerebroside found in the membranes of
macrophages
Consists of ceramide bonded to the hexose glucose

Galactocerebroside found almost exclusively


in the membranes of brain cells
Consists of ceramide joined to the monosaccharide
galactose

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(3) NONGLYCERIDE LIPIDS


Steroids
Are members of a large, diverse collection
of lipids called the isoprenoids (all of these
compounds are built from one or more 5carbon units called isoprene)
Terpene
Is the general term for lipids that are
synthesized from isoprene units
Steroids and bile salts, lipid-soluble vitamins
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(3) NONGLYCERIDE LIPIDS


Steroids
Contain the
steroid nucleus
(steroid carbon
skeleton)
Cholesterol
known steroid,
found in the
membranes
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(3) NONGLYCERIDE LIPIDS


Cholesterol
Amphipathic
Readily soluble in the hydrophobic region
of membranes
Involved in the regulation of the fluidity of
the membrane as a result of the nonpolar
fused ring
Hydroxyl group is polar
Perhydrocyclopentanophenantrene ring
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CHOLESTEROL
Can also exist in
an esterified form
called cholesteryl
ester, with the
hydroxyl group
conjugated by an
ester bond to a
fatty acid
No polar
groups making
them very
hydrophobic

CHOLESTEROL
Almost exclusively synthesized by animals,
but plants do contain other sterols similar in
structure to cholesterol
It is not readily catabolized by most cells,
therefore, does not serve as a source of
energy
Can be converted in the liver to primary bile
acids (e.g. cholic acid) and chenodeoxycholic
acid
Promote fat absorption in the intestine by acting as
detergent

(3) NONGLYCERIDE LIPIDS


Bile Salts
Are amphipathic derivatives of cholesterol
Synthesized in the liver and stored in the
gallbladder
Cholate
Chenodeoxycholate

Emulsifying agent whose polar hydroxyl


groups interact with water and whose
hydrophobic regions bind to lipids
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(3) NONGLYCERIDE LIPIDS


Steroid Hormones (Sex Hormones)
Testosterone
Progesterone
Estrone, Estrogen, and its derivatives
Cortisone and Cortisol
Aldosterone

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(3) NONGLYCERIDE LIPIDS


Waxes
Derived from many different sources and
have a variety of chemical compositions,
depending on the source
Paraffin wax

Long hydrocarbon tails extremely


hydrophobic completely insoluble in
water
Solid at RT
Lanolin protective coating for hair and skin
(used in skin creams and ointments)
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(4) COMPLEX LIPIDS


Complex Lipids
Are bonded to other types of molecules
Lipoproteins
Consist of a core of hydrophobic lipids
surrounded by amphipathic proteins,
phospholipids, and cholesterol

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LIPOPROTEINS
Typically spherical
in shape and range
in size 10 to 1200
nm
Composed of both
lipids and proteins,
called
apolipoproteins

LIPOPROTEINS
The larger the LPP
particles have larger
core regions
(contain relatively
more TAG and
cholesteryl ester)
The larger the LPP
also contain more
lipid relative to
CHON, therefore,
lighter in density

LIPOPROTEINS
Classification (based on ultracentrifugation)

Chylomicrons [chylos]
Very-low-density LPP [VLDL]
Low-density LPP [LDL]
High-density LPP [HDL]

APOLIPOPROTEINS
Primarily located on the surface of lipoprotein
particles
Help maintain the structural integrity of LPP
Serve as ligands for cell receptors
As activators and inhibitors of the various
enzymes that modify LPP particles

APOLIPOPROTEINS
Contain a structural motif called an
amphipathic helix, which accounts for the
ability of these proteins to bind to lipids

Are protein segments arranged in


coils so that the hydrophobic amino
acid residues interact with lipids
Helix containing hydrophilic amino
acid faces away from the lipids and
toward the aqueous environment

APOLIPOPROTEINS
Apo A-I
Major protein on HDL
Frequently used as an index of th
amount of the antiatherogenic HDL
present in plasma
Apo B
Is a large protein with MW 500 kD
Principal protein on LDL, VLDL, and
Chylomicrons
Apo B-100
Apo B-48

APOLIPOPROTEINS
Apo B-100
Is found on LDL and VLDL
Ligand for the LDL receptor
Critical in the uptake of LDL cells
Apo B-48
Exclusively found in chylomicrons
Can also be found covalently linked to
apo (a), a plasminogen-like protein
that is found in a proatherogenic LPP
particle called lipoprotein (a) [LP(a)]

APOLIPOPROTEINS
Apo E

Found in LDL, VLDL,a nd HDL


Serves as a ligand for the LDL
receptor and the chylomicron remnant
receptor
Apo E2
Apo E3
Apo E4
Affect LPP metabolism because they
differ in their ability to interact with the
LDL receptor

CHYLOMICRONS
Contain apo B-48
Account for the turbidity of postprandial
plasma

Readily float to the top of stored plasma and


form a creamy layer
chylous, turbid, milky, cloudy, lipemic
plasma/serum

CHYLOMICRONS
Produced by the intestine, where they are
packaged with absorbed dietary lipids
Once enter the circulation, TAG and
cholesteryl esters are hydrolyzed by lipase
Are transformed into chylomicron remnant
particles, which are taken up by remnant
receptors in the liver
Deliver dietary (exogenous) lipids to hepatic
and peripheral cells

VERY-LOW-DENSITY
LIPOPROTEIN
Contain apo B-100, apo E, and apo C
Produced by the liver
Rich in TAG like chylomicrons
Readily reflect light
Account for most of the turbidity observed in
fasting hyperlipidemic plasma specimens but
do not form a top, creamy layer

VERY-LOW-DENSITY
LIPOPROTEIN
Major carriers of endogenous (hepatic
derived) triglycerides
Transfer TAG from the liver to peripheral
tissue
Excess dietary intake of CHO, saturated fatty
acids, and trans fatty acids enhances the
hepatic synthesis of TAG, thus, increases
VLDL production

LOW-DENSITY LIPOPROTEIN
Contains apo B-100 and apo E
More cholesterol-rich than other apo Bcontaining lipoproteins
Primarily form as a consequence of the
lipolysis of VLDL
Readily taken up by cells via the LDL receptor
Accounts for the reason that elevated LDL levels
promote atherosclerosis

LOW-DENSITY LIPOPROTEIN
Significantly smaller than VLDL and
chylomicrons
Can infiltrate into the extracellular space of
the vessel wall, where it can be oxidized and
taken up by macrophages
Become filled up with intracellular lipid drops
and turn into foam cells
an early precursor of atherosclerotic plaques

HIGH-DENSITY
LIPOPROTEIN
Smallest and the most dense
Synthesized by both the liver and intestine
Can exist either as disk-shaped or as
spherical-shaped particles
Discoidal HDL
Contains 2 molecules of apo A-I
Represent newly secreted HDL
Most active form in removing excess cholesterol
from peripheral cells

HIGH-DENSITY
LIPOPROTEIN
Discoidal HDL
Acquire additional lipid, cholesteryl esters, and
TAG form a core region between the central lipid
bilayer, which transforms into spherical HDL
(predominant form in plasma)

Spherical HDL
HDL2

Larger in size and richer in lipid than


HDL3
May be more efficient in delivering lipids
to the liver
HDL3

REFERENCE RANGES
ANALYTE

REFERENCE RANGE

Total Cholesterol

140 200 mg/dL

HDL Cholesterol

40 75 mg/dL

LDL Cholesterol

50 130 mg/dL

Triglycerides

60 150 mg/dL

LIPOPROTEIN IN
ELECTROPHORESIS

Alpha-LPP = HDL
Pre-Beta LPP = VLDL
Beta-LPP = LDL

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METABOLISM

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