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

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

Fatty Acids
Saturated FA = no carbon doublebonds
Monounsaturated 1 C=C
double bond
Polyunsaturated > 2 C=C
double bonds
C=C causes bend (kink) in
molecule
Increases space needed when
compacted
More fluid or liquid oils at room
temp

OH

Lauricacid(12:0)

OH

Palmitoleicacid(16:1)

Clinical importance of fatty acids

Fecal fatty acids are sometimes measured to
detect malabsorptive and pancreatic
disordersthe 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

OH

CO

(CH2)n

CH3

OH

CO

(CH2)n

CH3

OH

CO

(CH2)n

CH3

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
There should be a form of
hydrophilic compound
Lipids are transported by a series
of micelles called lipoproteins

Triglycerides &
cholesteryl esters

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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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