Lipids & Lipoproteins

• Lipids are a diverse group of compounds

that have many biological functions
• They have 2 primary purposes in living
Organisms
– Storage of excess caloreis
• Composed mostly of carbon hydrogen (rich source
of energy)
– Structural role: Integral part of cell membrane
• Because of their unique structural design

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 Lipids
• The term lipid applies to a class of compounds that
are soluble in organic solvents and nearly insoluble in
water
• Some lipids contain non lipid groups (phosphoryl,
amino, sulfate)
• They are carried in the body by lipoproteins
– Lipoproteins allow fat to be dissolved into the plasma
• Subdivided into 4 main groups based on their
chemical structure
• Fatty acids
• Cholesterol
• Triglycerides
• Phospholipids

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 Fatty Acids
• Linear chains of carbon and hydrogen
– Terminate in -COOH carboxyl group
– Short chain = 4-6 carbons
– Medium = 6-12 carbons
– Long chain > 12 carbons
• Diet is mostly long chains with even number
of carbons

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 Fatty Acids
• Saturated FA = no carbon double-  
OH
bonds

• Monounsaturated → 1 C=C O

double bond Lauric acid (12:0)

• Polyunsaturated → > 2 C=C
double bonds
• C=C causes bend (kink) in
molecule OH

– Increases space needed when O

compacted
– More fluid or liquid → oils at room Palmitoleic acid (16:1)
temp

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Clinical importance of fatty acids

• Fecal fatty acids are sometimes measured to

detect malabsorptive and pancreatic
disorders—the test is mostly considered
obsolete
• Serum free fatty acids help distinguish
between hyperinsulinemic hypoglycemia
(FFA normal) and disorders of fatty acid
oxidation (FFA elevated and negative
ketones)

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 Triglycerides
• Glycerol backbone with FA attached by ester bonds
• Each FA can be different
• Triglycerides with saturated FA (no kinks)
– pack tightly → solid at room tempt
• Triglycerides with unsaturated FA typically oils at room temp

H H

H C OH H C O CO (CH2)n CH3

H C OH H C O CO (CH2)n CH3

H C OH H C O CO (CH2)n CH3

H H

Glycerol Triglyceride
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 Triglycerides

• Most plant-derived FA are highly

unsaturated
– Corn, safflower, sunflower, and peanut oils
• Most animal-derived saturated FA
– Usually solid at room temp
• Triglycerides → No charged groups or
polar hydrophilic groups
– Hydrophobic
– Not soluble in water

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 Triglycerides
• Source of Triglycerides:
– Exogenous source: Dietary
– Endogenous : Liver and tissue storage
• Triglycerides transported by Chylomicrons
(exogenous) and VLDL (endogenous)
• Energy source when plasma glucose is decreased
• Triglycerides catabolism is regulated by:
– lipase,
– Epinephrine,
– and cortisol

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 Phospholipids
• Similar in structure to
triglycerides
• Two FA – usually 14 - 24 C
long
– One saturated; one unsaturated
• Third spot has phospholipid
head group
• Several types of
phospholipid head groups
– Choline, serine, ethanolamine,
inositol

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 Phospholipids
• Phosphatidylcholine
– Have a choline head group
– Most common in lipoproteins and cell
membranes
• Phospholipids are Amphipathic lipid
molecules
– Hydrophobic FA and hydrophilic head group
• In Cell membrane
– Polar hydrophilic faces outward toward
aqueous environment
– Hydrophobic FA face inward away from
water

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 Cholesterol

• Unsaturated steroid alcohol - amphipathic

• 4 ring structures (A, B, C, D) with single side R
chain (like FA)
• Hydrophilic OH on A ring
• 4 rings and side chain internal, OH external

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 Cholesterol

• Primarily animal source

– Plants have other sterols
• Cholesterol not used as fuel source
– Not readily catabolized by cells
• Converted by liver to bile salts
– Promote fat absorption in bowel
• Converted to steroid hormones
– Vitamin D3
• Transported by HDL and LDL

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 Cholesteryl Ester

• Hydroxyl group bonded to FA

• Therefore no polar group → very
hydrophobic
• Generally found in center of lipid droplets
with triglycerides

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 Lipoproteins
• Lipids need to be transported to
tissues and organs to perform
their metabolic functions
• Triglycerides & cholesteryl esters
are hydrophobic Triglycerides &
• There should be a form of cholesteryl esters
hydrophilic compound
• Lipids are transported by a series
of micelles called lipoproteins

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 Lipoproteins
• General structure – spherical
– 10 - 1200 nm

– Lipoproteins composed of lipids &

proteins (apolipoprotein)
– Cholesterol and phospholipids on
surface monolayer
– Triglycerides and cholesterol esters
in center
• Main role is delivery of lipids

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 Lipoproteins
• Size correlates to lipid content
• Larger particles have more lipid core
– Relatively more triglycerides & cholesterol esters
– Larger lipid to protein ratio
– Lighter in density
• Various lipoproteins were separated by
ultracentrifugation into different density fractions:
• Chylomicrons,
• Very Low Density Lipoproteins (VLDL),
• Low Density Lipoproteins (LDL),
• High Density Lipoproteins (HDL)

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Lipoproteins

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 Apolipoproteins

• Apolipoproteins primarily on surface of

lipoprotein particle
– Maintain structural integrity
– recognition of cell surface receptors
– Activators & inhibitors of various enzymes that
modify lipoprotein particles
– Amphipathic helix
• Hydrophobic aa residues interact with lipids
• Hydrophilic aa resides interact with aqueous
environment

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 Apolipoproteins
• Apo A-1
• major protein of HDL
• Apo B
• Primary protein of LDL, VLDL and chylomicrons
• Apo C
• Chylomicrons, VLDL, HDL
• Apo E
• LDL, VLDL, HDL

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 Chylomicrons

• Contain apo B-48 lipoprotein

• Largest and least dense – up to 1200nm
• Large size reflect light – post-prandial
serum turbidity
• Float to the top – “cream” layer

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 Chylomicrons
• Produced by intestine, where
they are packaged with lipids
• Triglycerides and cholesterol
esters hydrolyzed by lipases
• Leaves chylomicron remnant →
liver recycled
• Therefore primary purpose is
transport of dietary lipid to liver
and peripheral cells

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 VLDL

• Contains apo B-100, apo E, Apo C

• Rich in endogenously derived triglycerides
from liver to cells
• Large size reflects light – fasting serum
turbidity
• Excess carbohydrates in diet, saturated FA
and trans FA increases hepatic synthesis of
triglycerides → hepatic synthesis VLDL
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 LDL

• Contain apo B-100 and apo E

• More cholesterol rich
• Form from lipolysis of VLDL
• LDL taken up by cells through receptor
– Part of reason behind atherosclerosis
• Up to 8 subclasses – still working on
diagnostic significance

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 LDL

• Significantly smaller than VLDL – can

embed in vessel walls
• Oxidized, taken up by macrophages
• Macrophages with too much lipid become
foam cells
• Become fatty streaks – precursor of
atherosclerotic plaques

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 Lipoprotein (a)

• LDL-like molecule
• Contain apo (a) linked to apo B-100
• Very heterogeneous number of peptide
sequences (kringles) in apo (a) portion
• Elevated Lp (a) increased risk for premature
coronary heart disease
– Kringle regions homology with plasminogen
– Compete with binding – increase clotting

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 HDL

• Smallest and most dense

• Synthesized by liver and intestine
• Discoidal HDL has 2 apo A-I molecules
– Forms a ring around phospholipids &
cholesterol
– Nascent/newly secreted HDL – active in
removal of excess cholesterol from peripheral
cells

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 HDL

• Discoidal HDL acquires additional lipids,

cholesterol esters & triglycerides form core
region = spherical HDL
• Spherical HDL predominate in plasma
• HDL transport lipids back to the liver from
peripheral tissues

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