Lipid pdf - د. باسل

LIPOPROTEINS

OBJECTIVE:



List the types of lipoproteins (LPs)

and

their

basic

structures.



Recognize the function of each LP in

transporting of cholesterol and TG.



Classify the LPs as exogenous, endogenous, bad

lipid, and the good (protective) lipid.

Definition:

All the types of Lipid components are

relatively water insoluble and therefore cannot be
transported into the blood throughout the body in their
native lipid forms (TGs, Phospholipids, FFAs,
cholesterol,

etc).

Lipoproteins(LPs)

are spherical structures composed

of native lipid components and specific proteins,
referred to apolipoproteins, function in transporting of
lipids throughout the human body.

To be able in

carrying the lipids

the no polar lipids directed to the

core, the TGs and Ech

while the relatively polar

components, Fch and phospholipids oriented to the
surface of the spherical structures

, and these structures

referred to

apolipoproteins(apoLPs).

Although,

the apoLPs still unable to be transported

throughout the body,

addition of sufficient amounts of

specific proteins, the

apolipoproteins

confer

the apoLP structures adequate polarity to be soluble and
transported in blood throughout the body.

Apoproteins

are

several

types

apoA;

I,II,III

apoB;

48,

100

apoC;

I,II,III

apoE;

2,3,4.

These apoproteins are poly peptide family function in

1. structural components of LPs, they are essential
constituents

for

integral

structures

2. some as cofactor for Enzymes involved in lipid
metabolism

as,

apoCII

,apoAI

3. some as ligand for recognition of whole particle of LPs by
their

receptor

apoE3,

apoB100

4. some aid in secretion of LP particles from the site of
origin

apoB48

from

small

intestine.

TYPES

LPs

There are five types that are involved in lipid function; They
are classified according to their density(ratio of
protein/lipid

content,

size).

The ascending order for classification of these LPs according
to their density (opposite for size) are as follow:

1.Chylomicrone(Exogenous lipid, TG-rich

particle)

2.Very Low Density Lipoprotein

VLDL

(Endogenous

lipid,

TG-rich

particle)

3.Intermediate

Density

Lipoprotein

IDL(Transient

lipid,

TG-Cholesterol)

4. Low Density Lipoprotein-Cholesterol

LDL-C

5. High Density Lipoprotein-Cholesterol

HDL-C

CHYLOMICRONE (Exogenous Lipid,TG-
rich particle):

Dietary lipid {90% TG+10%

(Phospholipids,  cholesterol,  Sphingolipids  &free  fatty
acids)  are digested and absorbed by small intestine in
enterocytes,  the  absorbed  lipids  are  resynthesized
again  into  TG,  PLs,    sphingolipids  &  small  amounts  of
FFAs

addition of apolipoproteins; mainly apoB48

Lipoprotein

Chylomicrone

the exogenous lipid.

So the Exogenous lipid source is small intestine which

secreted  into  lymphatic  system  (because  of  large  size
?),  blood  circulation,  where  Chylomicrone  acquired
apoCII  and  apoE,  both  are  important  for  their

metabolism.

Chylomicrons
◦ Synthesized in small
intestine
◦ Transport dietary lipids
◦ 98% lipid, large sized,
lowest density
◦ Apo B-48

involved in secretion

◦ Apo C-II

Lipoprotein lipase activator

◦ Apo E

Remnant receptor binding

Secreted  Circulated  Chylomicrone  transported  to
adipose tissue(A.T) & Muscles (cardiac+skeletal) where
it    hydrolyzed  (the  TG  content)  by  enzyme  Lipoprotein
Lipase  LPL  in  the  presence  of  apoCII  as  cofactor  (this
enzyme  coated  into  luminal  surface  of  blood  vessels
mainly of  A.T  ,  Sk.M and  Cardiac M).

The hydrolysis of

chylomicrone-TG

=FFAs+

glycerol.

FFAs are taken by A.T, Sk.M+ Cardiac M, while
glycerol

returned

the

liver.

The  chylomicron-    remnant  ,  which  contain  mainly
cholesterol,  apoE,apoB100  and  the  remainder  TG  10%
of original amount will be  taken up by the liver which
has receptor for Chylomicrone remnant recognized the
apoE3  on  the  surface  of  remnant  of  LPs.  This  engulfed
or  internalized  hepatic  remnant  used  in  endogenous
lipid

synthesis.

VLDL

(Endogenous

lipid,

TG-rich

particle):

This LP is synthesized in the Liver from the

remnant lipid of Chylomicrone & the Denovo
synthesized lipid in the liver (TG, PL+ cholesterol from
excess glucose and dietary FFAs

). ApoVLDL which after

addition of apoB100 and apoE3 is converted into LP
VLDL.

It is secreted directly into blood circulation where

it  acquired  apoCII,  the  cofactor  of  ?.  Then  as
Chylomicrone  undergoes  the  removal  of  significant
amount  of  TG  by  LPL  in  A.T,  Sk.M  &  cardiac  M.

The

remainder component of this metabolism referred to
IDL which contains equal amount of TG and cholesterol
in addition to apoE3 and apoB100.

IDL

is transient LP component, 50% of which is retaken

by the liver via hepatic receptor recognized apoE3,
while the remainder 50% are converted into LDL after
removal

all

from

IDL.

LDL

is exclusively cholesterol containing particle

with          only  apoB100  as  apoLP,  it  is  synthesized  from
VLDL  in  the  circulation  and  it  is  the  carrier,  mainly  of
cholesterol  from  the  principal  site  of  synthesis,  the
liver,  to  the  peripheral  tissues  such  as  the  endocrines,
skin,…,  etc.  LDL-C  is  the  more  dense  and  smaller  size
compared  with  chylomicrone  and  VLDL,  so  it  is  the
Atherogenic lipid, means its blood concentrations have
the  direct  correlation  with  risk  and  the  incidence  of
coronary heart disease CAD.

You  must  know  that  this  lipid  LDL  is  subdivided  into  several
fractions  LDL1  to  LDL  9,  of  which  the  LDL5  may  be  the
atherogenic  one.  Also,  the  native  LDL-C  molecule  is  not
atherogenic  by  itself,  but  the  modified,  such  as  the  oxidized
LDL-C

the

atherogenic

lipid.

The control of blood LDL level is by two ways:

1.  Hepatic  tissue  receptors;  the  hepatic  LDL  receptor
which  account  for  2/3  removal  of  blood  LDL  and  is
regulable  and  saturable  mechanism.  These  LDL  receptors
recognize  the  apoB100  found  on  the  surface  of  LDL-C
molecules  and  the  complex  of  LDL-Receptor  internalized  by
hepatic  cells  and  so  regulate  the  blood  cholesterol

concentrations.

2.  Scavenger  receptor  1/3  of  blood  LDL  and  is  found  in
many  cell  of  tissues  but  predominant  in  Macrophage
cells  (the  native  of  them  are  Monocyte  cells)  and  it  is
nonsaturable

and

not

regulated

blood

LDL.

The vascular

sub endothelial LDL-rich macrophages

are the precursors and the early step in plaque
synthesis and consequent atherosclerosis.

The

entered LDL-C

to the liver regulates blood

cholesterol concentration by the following ways:

1. decreased the HMG-CoA reductase enzyme, so
decrease the endogenous cholesterol synthesis

2. Increased Acyl Cholesterol Acyl Transferase

(ACAT)

enzyme, which increased the intracellular cholesterol
synthesis,

the

less

toxic

cholesterol.

3. decreased the LDL-C receptor synthesis by inhibition
of gene expression to lower the LDL-C endocytosis and
prevents the intracellular cholesterol accumulation.

HDL-C

is cholesterol-rich particle and the

protective lipid. Its blood concentrations have inverse
correlation with the risk and the incidence of CAD.

It is

the carrier LP of excess amounts of cholesterol from the
peripheral tissues, such as the HEART (intracellular and
cell membranes) and returned it to the Liver, the only
route

for

removal

excess

cholesterol.

There  are  HDL3  and  HDL2  which  differ  in  their
cholesterol  content.  HDL2  is  more  cholesterol-
containing particle than HDL3.  The reversed cholesterol
by HDL must be esterified  to be captured and returned
to  liver.  LCAT,  Lecithin  Cholesterol  Acyl  Transferase,  is
the  enzyme  responsible  about  esterification  in  the
presence

cofactor

apoAI.

CETP: Cholesterol Ester Transfer Protein.