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

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 (2) GLYCERIDES
• Phosphatidylethanolamine (Cephalin)
– Similar in general structure to lecithin

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 (3) NONGLYCERIDE LIPIDS
• Sphingolipids
– Are lipids that are not derived from glycerol
– Amphipathic and structural components of
cellular membranes

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 (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

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 (3) NONGLYCERIDE LIPIDS
• Glycosphingolipids (Glycolipids)
– 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
• ________________ – found in the membranes of
macrophages
– Consists of ceramide bonded to the hexose glucose
• ________________ – 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 5-
carbon 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

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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

– 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)

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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 @ room temp
• 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
 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)
 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 the
amount of the antiatherogenic HDL
present in plasma
 APOLIPOPROTEINS
• 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
 APOLIPOPROTEINS
• 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
 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

 VERY-LOW-DENSITY
LIPOPROTEIN
• Major carriers of endogenous (hepatic
derived) triglycerides

• 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 B-
containing lipoproteins

• 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
NEXT ON BIOCHEMISTRY:

METABOLISM

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