METABOLISME KOLESTEROL,

LIPOPROTEIN DAN
APOLIPOPROTEIN
Meizly Andina
DEPARTEMEN BIOKIMIA
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH SUMATERA

Cholesterol is present in tissues and in

plasma either as:
Free cholesterol or

as a storage form, combined with a long-chain

fatty acid as cholesteryl ester.

In plasma, both forms are transported in

lipoproteins
Cholesterol is an amphipathic lipid and as
such is an essential structural component
of membranes and of the outer layer of
plasma lipoproteins.

 Cholesterol

is obtained from

the diet
or synthesized by a pathway that occurs

in most cells of the body,

but to a greater extent in cells of the
liver and intestine.

The precursor for cholesterol

synthesis is acetyl CoA, which
can be produced
from

glucose
fatty acids,
amino acids.

Metabolisme
cholesterol
Fungsi cholesterol :
Membentuk garam empedu
Integritas membran
Membentuk hormon steroid
Membentuk Vitamin D3

Absorpsi dan transportasi

lipid
Free Fatty acids, free cholesterol dan

2- monoacylglycerol .
Resintesa TG dan Cholesteryl ester
didalam sel-sel mucosa usus
Enzim Fatty acyl CoA synthetase
(Thiokinase) mengaktifkan FA
FA
rantai
sedang
dan
pendek
langsung ke sirkulasi porta dan
ditransport oleh Albumin.
Lipid
lainnya
ditransport
oleh
Chylomicron
didalam
pembuluh

Transportasi
lipid
TG

dari Chylomicron dihydrolisa oleh

enzim Lipoprotein lipase
Chylomicron remnant.
Hepar mensynthese TG, ditransport oleh
VLDL
Dihydrolisa oleh Lipoprotein lipase
IDL
LDL (22 nm, memp. 1500 molekul
ester Cholesterol dng Linolat)
LDL diselubungi oleh : - Phospholipid
- Cholesterol non

Transportasi
lipid
Fungsi LDL : - transport cholesterol ke
jaringan peripher
- kontrol synthese de novo
cholesterol di jaringan
HDL : transport cholesterol dari
jaringan rusak/mati kesirkulasi. Oleh
Acyltransferase cholest. ini
diesterifikasi dan oleh protein transfer

Lipoprotein general
structure

Lipoproteins are characterized according to their

densities.

The lipoprotein densities vary depending on their

lipid composition.

The free hydroxyl group of cholesterol is exposed

on the surface of the lipoprotein to interact with
water. These proteins are referred to as
apoproteins.

APOLIPOPROTEINS
Apolipoproteins are the protein
components of the lipoproteins. They
are important in :
1. Maintaining the structural integrity
of the lipoproteins
2. Regulaton certain enzymes which
act on lipoproteins
3. Receptor recognition

Properties of Some Human

Apolipoproteins

STRUCTURE OF
LIPOPROTEIN

Composition of the Lipoproteins

in Plasma of Humans

Lipoprotein Composition

LIPOPROTEIN
FUNCTIONS

Four classes of lipoproteins, visualized in the electron microscope

after negative staining.

Chylomicrons, 50 to 200 nm in diameter; VLDL, 28 to 70 nm; HDL, 8 to
11 nm;
and LDL, 20 to 25 nm.

Molecular structure of a chylomicron

The surface is a layer of phospholipids,

with head groups facing the aqueous
phase. Triacylglycerols sequestered in the
interior (yellow) make up more than 80% of
the mass. Several apolipoproteins that
protrude from the surface (B-48, C-III, C-II)
act as signals in the uptake and
metabolism of chylomicron contents. The
diameter of chylomicrons ranges from
about 100 to 500 nm.
Synthesized in small intestine
Transport dietary lipids
98% lipid, large sized, lowest density
Apo B-48
Receptor binding
Apo C-II
Lipoprotein lipase activator
Apo E
Remnant receptor binding

LIPOPROTEIN
METABOLISM
The two key enzyme systems are
involved in lipoprotein metabolism,
example :
1.

Lipoprotein lipase releases free

fatty acids and glycerol from
chylomicrons and VLDL into the
tissues

2.

Lechitin cholesterol acyl transferase

Metabolic fate of chylomicrons. (A, apolipoprotein A; B-48, apolipoprotein B-48; ,

apolipoprotein C; E, apolipoprotein E; HDL, high-density lipoprotein; TG, triacylglycerol; C,
cholesterol and cholesteryl ester; P, phospholipid; HL, hepatic lipase; LRP, LDL receptorrelated protein.) Only the predominant lipids are shown.

VERY LOW DENSITY

LIPOPROTEIN (VLDL)

Very low density lipoprotein (VLDL) is

formed in the liver from triacylglycerol and
cholesterol provided by the tissue and
with the assistance of apoprotein B-100.

It is mostly made in the body (90%) with a

small portion (10%) derived from the diet.

LIPID
MOBILIZATION

The VLDL is exported and picks up apoprotein CII

and E in the blood. Note that since LDL is derived
from VLDL, the VLDL molecule contains the
apoproteins needed for both VLDL and LDL
functions.

The role of VLDL is to transport and deliver fatty

acids to peripheral tissues. Triacylglycerols
contained in VLDL, as in chylomicrons, are
substrates for lipoprotein lipase in capillaries.

LIPID
mature MOBILIZATION
VLDL reaches the peripheral

The
tissues
(adipose tissue and skeletal and cardiac muscles) where
it is acted upon by the enzyme plasma lipoprotein lipase
(LPL) which needs apoCII for its activation.

The action of this enzyme results in hydrolysis of

triglycerides into glycerol and free fatty acids.

The fatty acids are taken up by the cells in these tissues

and are either used in the production of energy (skeletal
and cardiac muscles) or used in the synthesis of tissue
or milk fat (adipose tissues and lactating mammary
glands.

 After

LIPID
MOBILIZATION

losing the main bulk of its

triglycerides, the VLDL returns the
apoC back to the HDL and become
VLDL remnants (IDL).

Then

VLDL remnants give their apoE

back to the HDL and become LDL.

LIPID
MOBILIZATION

Characteristics of Common
Hyperlipidemia

Clinical Manifestations of
Hyperlipidemia
Xanthelasma

Severe
xanthelasma and
arcus cornea

Tuberous
xanthoma

Large tuberous
xanthoma of elbow

Eruptive
xanthoma

Xanthoma of
extensor tendons
of the hands

Xeroradiogram
of Achilles
tendon
xanthoma

Xanthoma of
Achilles
tendon

Lipoprotein Metabolism and

Atherosclerosis

Atheroma in Artery

Log-linear relationship between LDL-C levels and

relative risk for CHD

Sekian