Lipoproteins

• particles found in plasma that transport

lipids including cholesterol
• lipoprotein classes
• chylomicrons: take lipids from small
intestine through lymph cells
• very low density lipoproteins (VLDL)
• intermediate density lipoproteins (IDL)
• low density lipoproteins (LDL)
• high density lipoproteins (HDL)
 Lipoprotein Density (g/ Diameter Protein % Phospholipi Triacylglycerol
class mL) (nm) of dry wt d % % of dry wt
HDL 1.063-1.21 5 – 15 33 29 8

LDL 1.019 – 1.063 18 – 28 25 21 24

IDL 1.006-1.019 25 - 50 18 22 31

VLDL 0.95 – 1.006 30 - 80 10 18 50

chylomicrons < 0.95 100 - 500 1-2 7 84

Composition and properties of human lipoproteins

most proteins have densities of about 1.3 – 1.4 g/mL and lipid aggregates usually
have densities of about 0.8 g/mL
Lipoprotein structure
LDL molecule
 The apolipoproteins
• major components of lipoproteins
• often referred to as apoproteins
• classified by alphabetical designation (A-E)
• the use of roman numeral suffix describes the
order in which the apolipoprotein emerge from
a chromatographic column
• responsible for recognition of particle by
receptors
 LIPOPROTEINS
• spherical particles with a hydrophobic
core (TG and esterified cholesterol)
• apolipoproteins on the surface
• large: apoB (b-48 and B-100)
• smaller: apoA-I, apoC-II, apoE
• classified on the basis of density and
electrophoretic mobility (VLDL; LDL;
IDL;HDL)
Apoproteins of human lipoproteins
• A-I (28,300)- principal protein in HDL
• 90 –120 mg% in plasma; activates LCAT
• A-II (8,700) – occurs as dimer mainly in HDL
• 30 – 50 mg %; enhances hepatic lipase activity
• B-48 (240,000) – found only in chylomicron
– <5 mg %; derived from apo-B-100 gene by RNA
editing; lacks the LDL receptor-binding domain of
apo-B-100
• B-100 (500,000) – principal protein in LDL
• 80 –100 mg %; binds to LDL receptor
Apoproteins of human lipoproteins
• C-I (7,000) – found in chylomicron, VLDL, HDL
• 4 – 7 mg %; may also activate LCAT
• C-II (8,800) - found in chylomicron, VLDL, HDL
• 3 – 8 mg %; activates lipoprotein lipase
• C-III (8,800) - found in chylomicron, VLDL, IDL, HDL
• 8 – 15 mg %; inhibits lipoprotein lipase
• D (32,500) - found in HDL
• 8 – 10 mg %; also called cholesterol ester transfer protein (CETP)
• E (34,100) - found in chylomicron, VLDL, IDL, HDL
• 3 – 6 mg %; binds to LDL receptor
• H (50,000) – found in chylomicron; also known as β-2-
glycoprotein I (involved in TG metabolism)
Type Association Function

B48 Chylomicron Carry cholesterol esters

Lacks LDL recpt
binding domain

B100 VLDL,IDL,LDL Binds LDL recpt.

C-II Chyl. VLDL, IDL, HDL Activates LPL

C-III Chyl. VLDL, IDL, HDL Inhibits LPL

E Chyl. Remnant, VLDL, IDL Binds LDL recpt

HDL

A-1 HDL/Chylomicron LCAT activator

(lecithin cholesterol
acyltransferase)
 Major lipoprotein classes
• Chylomicrons (derived from diet)
– density <<1.006
– diameter 80 - 500 nm
– dietary triglycerides
– apoB-48, apoA-I, apoA-II, apoA-IV, apoC-II/
C-III, apoE
– remains at origin in electrophoretic field
 Chylomicron
• formed through extrusion of resynthesized
triglycerides from the mucosal cells into the intestinal
lacteals
• flow through the thoracic ducts into the subclavian
veins
• degraded to remnants by the action of lipoprotein
lipase (LpL) which is located on capillary endothelial
cell surface
• remnants are taken up by liver parenchymal cells due
to apoE-III and apoE-IV isoform recognition sites
Chylomicron metabolism
 Major lipoprotein classes
• VLDL
– density >1.006
– diameter 30 - 80nm
– endogenous triglycerides
– apoB-100, apoE, apoC-II/C-III
– prebeta in electrophoresis
– formed in the liver as nascent VLDL
(contains only triglycerides, apoA and apoB)
 VLDL
• nascent VLDLs then interact with HDL to
generate mature VLDLs (with added
cholesterol, apoC-II and apoC-III)
• mature VLDLs are acted upon by LpL to
generate VLDL remnants (IDL)
• IDL are further degraded by hepatic
triglyceride lipase (HTGL) to generate
LDLs
VLDL metabolism
 Major lipoprotein classes
• IDL (intermediate density lipoproteins)
– density: 1.006 - 1.019
– diameter: 25 - 35nm
– cholesteryl esters and triglycerides
– apoB-100, apoE, apoC-II/C-III
– slow pre-beta
 Major lipoprotein classes
• LDL (low density lipoproteins)
– density: 1.019 - 1.063
– diameter: 18-25nm
– cholesteryl esters
– apoB-100
– beta (electrophoresis)
– < 130 LDL cholesterol is desirable, 130-159 is
borderline high and >160 is high
 Major lipoprotein classes
• HDL (high density lipoproteins)
– density: 1.063-1.210
– diameter: 5-12nm
– cholesteryl esters and phospholipids
– apoA-I, apoA-II, apoC-II/C-III and apoE
– alpha (electrophoresis)
 Functions of HDL
• transfers proteins to other lipoproteins
• picks up lipids from other lipoproteins
• picks up cholesterol from cell membranes
• converts cholesterol to cholesterol esters via the
LCAT reaction
• transfers cholesterol esters to other lipoproteins,
which transport them to the liver (referred to as
“reverse cholesterol transport)
Cholesterol and lipid transport by
lipoproteins
Cholesterol and lipid transport by
lipoproteins
 Liver
Dietary TG
CE Apo B48

cholesterol
Apo B48
CII
FFA FFA-FABP TG
TG/CE
micelle
A
CIII

chylomicron
ER/golgi

enterocyte

Plasma
Plasma
TG
B48 FFA
Oxidation
CII
muscle
TG/CE Lipoprotein
CIII Lipase

chylomicron

Lipoprotein B48 CII

FFA Lipase
TG/CE
CIII
FFA E
Chylomicron remnant
G3P liver

Triglyceride adipose
storage
Endogenous Lipid Transport
Plasma Dietary Carbohydrate
LIVER

glucose pyruvate Acetyl CoA

B48 LDL receptor Acetyl CoA

E mitochondria
TG/CE
TG
Cholesterol
CMr
(endogenous)
cholesterol
B100
(exogenous)

CE/TG VLDL
FFA FFA TG

VLDL
 From liver Cholesterol.
In bile LIVER
Endogenous cholesterol
B100 E

CII
CE/TG

VLDL B100 E
LDL receptor
CE/TG

IDL E

B100
LPL FA CE

FFA LDL Extrahepatic tissue

muscle LDL receptor

adipose
 LDL
Liver

Dietary fat Bile salts Endogenous

cholesterol
extrahepatic
small Exogenous tissue
intestine cholesterol

HDL
chylomicrons
chylomicrons reminants
VLDL

IDL

capillaries

Lipoprotein Lipase Lipoprotein Lipase

FFA FFA
Adipose, muscle