Metabolism of Lipids And: Lipoproteins

Metabolism of Lipids and
Lipoproteins
Ajeng Diantini
Lipids and Cardiovascular Disease

Evidence suggests :
there is positive correlation between the risk of developing
ischaemic heart disease and plasma LDL-cholesterol levels
and a negative one with those of HDL-cholesterol
Atherogenesis
Lipid theory
Response to Injury theory
Mesenchymal theory
Mutagenic theory
Factors of Coronary Heart

Diseases
Cardiovascular Risk Factors
Major Lipids of the Body
Triglicerides (Triacylglycerols) : energy

reservoir,
Structural components of membranes:

Cholesterol : precursor for steroid hormones
and bile acids
Phospholipids: lipid complex consisting
phosphate and a nitrogenous base.
Glycolipids
In blood stream, lipids are transported in the
form of lipoproteins.
After a fatty meal: the main of ingested TAG in the

mucosal cells is absorbed into the lymph as
chylomicrons which enter the blood mainly
through the thoracic duct
Adipose tissue
Lipoprotein lipase (clearing factor lipase)
precursor of LPL is synthesized in the
adipocytes and transferred to an outer membrane
of the cells, where it is activated by heparin or
related proteogycan, then transported to the
endothelial cells of adipose tissue.
LPL controlled by insulin (promote activation), and
adrenalin (inhibit activation).
Apo C-II is a cofactor for lipoprotein lipase, and

this apoprotein is transferred from HDL to
chylomicrons or VLDLs to activate the enzyme
when they reach endothelial cells.
At the endothelial cells: hydrolysis of TAG of

chylomicrons to monoglycerol + FFA.
2 FFA + monoacylglycerol from each TAG cross the

cell membrane. MonoAG subsequently hydrolysed
to glycerol + FFA (by monoAG hydrolase).
Glycerol is released to circulation but the FA are
retained and synthesized into TAG in adipose
tissue cells.
Fase penetrasi sel dan intra luminal

absorpsi trigliserida
Fase seluler absorpsi trigliserida
ROLE OF GLUCOSE AND INSULIN

After normal mixed meal,the plasma
glucose will rise and this cause the rise of
insulin plasma. Insulin enhances the
activation of LPL, so that circulating TAG
are rapidly taken un into tissues.
Glucose also plays an important role in the
provision of glycerol-3-phosphate for the
synthesis of TAG from FFA taken up from
the chylomicrons.
Catabolism of Triglyceride
Lipid transport in the fasting state
Chylomicrons clearing : 10 hours, then the

adipose tissue may begin to release its store of
TAG (by hs-Lipase)
Lipoprotein are water-soluble complexes

of high molecular weight composed of
lipids (cholesterol, triglycerides,
phospholipids) and one or more specific
proteins, called apolipoprotein.
Function of lipoproteins:
Transport for water-insoluble lipids in the
blood
Structure :
They form particles in which the hydrophilic moieties
of the phospholipids and apolipoproteins are arrange
at the surface and the hydrophobic triglycerides and
cholesteryl esters are oriented toward the interior to
Classification:
The lipoproteins are divided into various

categories according to density, as
determined by ultracentrifugation
Chylomicrons:
D < 0.95 g/ml
Formed in the intestine, transport
exogenous triglycerides
Composed of 98 99.5 % lipid and 0.5
2 % protein
Float to form a superficial layer on serum
allowed to stand overnight.
Lipoptroteins
LDL (Low-density Lipoproteins)
d = 1.019 1.063 g/ml
transport cholesterol in the blood
LDL arises as metabolic products of VLDL
Contain approx. 75 % lipid and 25 % protein

HDL (High Density Lipoproteins)
d = 1.063 1.21 g/ml
contain approx. 50 % lipid and 50 % protein
are produced by the intestine and liver in precursor form,

then fully developed in plasma.
Capable of taking up cholesterol from cells and

transporting it back to the liver.
HDL subfractions : HDL1 (1.055-1.085 g/ml), HDL2

(1.063 -1.15 g/ml) and HDL 3 (1.15 1.21 g/ml)
VLDL (Very Low Density Lipioproteins)
d < 1.006 g/ml
formed in the liver, transport endogenous

triglycerides
consist of 85 90 % lipid and 10-15 protein.

IDL (Intermediate-density Lipoproteins)
d = 1.006 1.019 g/ml
found in the absence of metabolic diseases only

in very low concentration
are thought to be metabolic products of VLDL or

precursor particles of LDL
Lipoproteins
separated by
-lipoproteins (LDL)
electrophoresis
are classified as:
pre - lipoproteins (VLDL)

-lipoproteins (HDL)
The triglyceride-rich chylomicrons show almost no
migration at all and remain at the origin on
supporting media.
The -lipoproteins migrate with the -globulin.
pre - lipoproteins migrate with 2-globulins
-lipoproteins with 1-globulins
Apolipoprotein
Apolipoproteins
Lipoproteins and apolipoproteins
Esterification of Cholesterol
Biosynthesis of HDL-Cholesterol
Internalization of LDL into the cell
Metabolic pathways of lipid and

lipoproteins
Major function of the plasma lipoprotein :
is transport of triglyceride from sites of synthesis in
the intestine or liver to sites of storage (adipose
tissue), energy use (muscles), or metabolism (liver).
PROTECTIVE HDL
HDL is a Reverse Cholesterol
Transport. HDL decreased LDL oxidation
(have an antioxidant function). Paraoxonase (enzyme present in HDL)
Prevents the accumulation of
Lipoperoxides in LDL. HDL decreased expression of VCAM-1,
ICAM-1 and E-Selectin, induced
By TNF-.-
WHO Classification of hyperlipoproteinaemia
Disorder of lipid metabolism
Hypertriglyceridemia :
high level of chylomicron , VLDL or both.
turbid plasma
associated with abdominal pain, pancreatitis, or symptom
free.
reduce HDL, and/or increase LDL
Hypercholesterolemia:
- with little or no elevation of TG, often is almost always
due to raised LDL levels.
- Main disorders that may produce a secondary increase
LDL and total chol:
hypothyroidism, diabetes mellitus, nephrotic syndrome,
cholestasis
Hyperchylomicronaemia:
- deficiency of LPL (lipoprotein lipase)
Rare disorder of lipid metabolism
deficiencies of HDL ---- premature CHD

- abnormal Apo A result in excessive catabolism
of HDL
Apo B deficiency ( abetalipoproteinemia, LDL
def) : impaired synthesis of chylomicron and
VLDL.
------ steatorrhea
Deficiency of LCAT --- accumulation of free
chol----- premature atherosclerosis
LIPIDS & LIPOPROTEINS

ANALYSIS.-
Cholesterol
Triglyceride
LDL-Cholesterol
HDL-Cholesterol
Apo B
Lp (a)
Small-Dense LDL
Ox-LDL
Parameter of Dislipidemia:
How far and why?
Chylomicron
Triglyceride
Total cholesterol
Cholesterol-LDL
Cholesterol-HDL
Apo-A
Apo-B
Ratio Apo A/Apo B
Ratio Total Chol/HDL
CRP
Strong pedictor of :
1. Myocardial infarction
2. Stroke
3. Peripheral vascular disease
4. Sudden cardiac death in individuals
without a history of heart disease
Role of CRP in
atherogenesis
Local endothelial cell surface adhesion

molecule
2. Monocyte chemoattractan protein-1
3. Endothelin-1
4. Endothelial plasminogen activator inhibitor-1
CRP also:
1. Reduces endothelial nitric oxide bioactivity
2. Increases the induction of tissue factor on
monocyte and LDL uptake og macrophage
3. Co-localizes with the complement MAC
(membrane attack complexes) within artery
lession
1.
Homocystein
Increased concentration of total
homocystein (tHcy) correlate with CHD
Sulfur-containing amino acid with each
molecule of Hcy containing one atom of
sulfur
It is formed during metabolism of
methionine and requires folic acid as cofactor

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Metabolism of Lipids and

Lipids and Cardiovascular Disease

Factors of Coronary Heart

Cardiovascular Risk Factors

Major Lipids of the Body

Triglicerides (Triacylglycerols) : energy

Structural components of membranes:

After a fatty meal: the main of ingested TAG in the

Apo C-II is a cofactor for lipoprotein lipase, and

At the endothelial cells: hydrolysis of TAG of

2 FFA + monoacylglycerol from each TAG cross the

Fase penetrasi sel dan intra luminal

Fase seluler absorpsi trigliserida

ROLE OF GLUCOSE AND INSULIN

Lipid transport in the fasting state

Chylomicrons clearing : 10 hours, then the

Lipoprotein are water-soluble complexes

The lipoproteins are divided into various

LDL (Low-density Lipoproteins)

d = 1.019 1.063 g/ml

transport cholesterol in the blood

LDL arises as metabolic products of VLDL

Contain approx. 75 % lipid and 25 % protein

d = 1.063 1.21 g/ml

contain approx. 50 % lipid and 50 % protein

are produced by the intestine and liver in precursor form,

Capable of taking up cholesterol from cells and

HDL subfractions : HDL1 (1.055-1.085 g/ml), HDL2

VLDL (Very Low Density Lipioproteins)

d < 1.006 g/ml

formed in the liver, transport endogenous

consist of 85 90 % lipid and 10-15 protein.

d = 1.006 1.019 g/ml

found in the absence of metabolic diseases only

are thought to be metabolic products of VLDL or

pre - lipoproteins (VLDL)

Lipoproteins and apolipoproteins

Internalization of LDL into the cell

Metabolic pathways of lipid and

WHO Classification of hyperlipoproteinaemia

Disorder of lipid metabolism

Rare disorder of lipid metabolism

deficiencies of HDL ---- premature CHD

LIPIDS & LIPOPROTEINS

Local endothelial cell surface adhesion

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