Chapter 16 (Part 1)
Lipid Absorption and
Mobilization
Lipoproteins
• Transport water insoluble
TAG, cholesterol and
cholesterol-esters
throughout circulatory
system
• Hydrophobic core containing
TAG and cholesterol-esters
• Hydrophillic surface made of
proteins (apoproteins) and
phospholipids)
Lipoproteins
• Several different classes of lipoproteins.
• Chylomicrons deliver dietary fats to tissues
• VLDL, IDL and LDL transport endogenously
synthesized TAG and cholesterol to tissues
• HDLs remove cholesterol from serum and
tissues and transports it back to the liver.
• VLDL, IDL, LDL, and HDL named based on
their density. Low density lipoproteins have
high lipid to protein ratios. High density
lipoproteins have low lipid to protein ratios.
Lipoproteins
• Lipases in capillaries of adipose and
muscle tissues degrade TAG in
VLDLs. VLDLs become IDLs.
• IDLs can then give up more lipid
and become LDLs.
• LDLs are rich in cholesterol and
cholesterol-esters.
Apolipoproteins
• VLDLs, IDLs, and LDLs all contain a large
monomeric protein called ApoB-100.
• ApoB-100 forms amphipathic crust on
lipoprotein surface.
• Chylomicrons contain analogous lipoprotein
ApoB-48.
• VLDLs and IDLs also possess a number of small
weakly associated proteins that disassociate
during lipoprotein degradation.
• Small apolipoproteins function to modulate the
activity of enzymes involved in lipid mobilization
and interactions with cell surface receptors.
LDL Receptor
• Binds to ApoB-100.
• Found on cell surface of many cell types
• Mediates delivery of cholestrol by inducing
endocytosis and fusion with lysosomes.
• Lysosomal lipases and proteases degrade the
LDL. Cholesterol then incorporates into cell
membranes or is stored as cholesterol-esters.
High LDL levels can lead to
cardiovascular disease.
• LDL can be oxidized to form oxLDL
• oxLDL is taken up by immune cells called
macrophages.
• Macrophages become engorged to form
foam cells.
• Foam cells become trapped in the walls
of blood vessels and contribute to the
formation of atherosclerotic plaques.
• Causes narrowing of the arteries which
can lead to heart attacks.
Plaque Build up in Artery
Absence of LDL Receptor Leads
to Hypercholesteremia and
Antherosclerosis
• Persons lacking the LDL receptor suffer from
familial hypercholestermia
• Result of a mutation in a single autosomal gene
• Total plasma cholesterol and LDL levels are
elevated.
• Homozygous indivdiuals have cholesterol levels
of 680 mg/dL. Heterozygous individuals = 300
mg/dL. Healthy person = <200 mg/dL.
• Most homozygous individuals die of
cardiovascular disease in childhood.
LDLs/HDLs and Cardiovascular
Disease
• LDL/HDL ratios are used as a diagnostic tool
for signs of cardiovascular disease
• LDL = “Bad Cholesterol”
• HDL = “Good Cholesterol”
• A good LDL/HDL ratio is 3.5
• Protective role of HDL not clear.
• An esterase that breaks down oxidized lipids
is associated with HDL. It is possible (but
not proven) that this enzyme helps destroy
oxLDL
Triacylglycerols are Highly
Concentrated Energy Stores
• Complete oxidation of fatty acids yield 9
kcal/gm while only 4 kcal/gm are
generated from carbos and proteins.
• Fatty acids are more reduced than
proteins or carbos.
• Since TAGs are non-polar and anhydrous
(lacking hydration shell), can store more
than 6 times as much energy per gm
than glycogen.
Energy Reserves of a 150 lb Man
• 100,000 kcal of TAG, 25,000 kcal
protein, 600 kcal glycogen, 40 kcal
glucose.
• 24 lbs of body weight is TAG
• Would need 121lbs of glycogen to
store the same amount of energy
Absorption and Mobilization of TAG
• Digestion of dietary lipids occurs in the small
intestine.
• TAG must be broken down to fatty acids for
absorption across intestinal epithelium.
• First TAG forms micelles with bile salts
(amphipathic molecules drived from cholestrol)
• The micelles form to orient ester bonds of TAG
towards the hydrophillic surface to allow water
soluble lipases to cleave molecule.
Bile Salt
• Fatty acids and MAG enter mucosal cells where
they are used to re-synthesize TAG
• TAG is then packaged into lipoprotein transport
particles called chylomicrons (lipoprotein).
• Chylomicrons are mainly composed of TAG and
apoprotein B-48. Also contain fat solubel vitamins
• Chylomicrons enter the lymph system and then the
blood stream.
• Chylomicrons bind to membrane bound lipoprotein
lipases at the surface of adipose and muscle cells.
Storage of FAT
• TAG is delivered to
adipose tissue in the
form of chylomicrons and
VLDLs.
• The TAG is hydrolyzed
and enters adipose cell
as free fatty acid and
MAG.
• Fatty acids and MAG are
re-esterified to form
TAG.
• TAG coalesce in the
cytoplasm of adipose
cells to form large
globules
Mobilization of Fat
• Epinephrine,
noepinephrine, glucgon
and
adrenocorticotrophic
hormones activate an
adipose lipase.
• The hormones bind to
the 7M receptor on
outer surface of the
adipose cell plasma
membrane.
• Induces a G-protein
mediated signal
transduction pathway.
Mobilization of Fat
• Free fatty acids are not soluble in blood plasma.
• Fatty acids are carried through the blood stream
on proteins called serum albumins.
• Once fatty acids reach target cell it enters the
cell and becomes esterified to CoA-SH and enters
b-oxidation pathway
• Glycerol generated from fat breakdown is
absorbed by the liver it can serve as an
intermediate for glycolysis or gluconeogenesis.