Download Lipid and Lipoprotein Population Distributions - Lectures For UG-5

LIPIDS AND LIPOPROTEINS
LIPID CHEMISTRY AND CARDIOVASCULAR
PROFILE
Main lipids in the blood are the
triglycerides and cholesterol.
 Insoluble in the water.
 Transport in the blood is via lipoproteins

TRIGLYCERIDES

Glycerol with 3 attached fatty acids

Exogenous source : Dietary
Endogenous : Liver and tissue storage
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95 % of body fat is triglycerides
Energy source when plasma glucose is decreased
Triglyceride catabolism is regulated by lipase, epinephrine
and cortisol
Triglycerides transported by Chylomicrons ( exogeneous )
and VLDL ( endogenous )
CHOLESTEROL



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

Found only in animals
Important component of membranes, steroid hormones, bile and
Vitamin D
Exogeneous cholesterol comes from diet
Endogeneous cholesterol is synthesized by the liver
70 % of cholesterol associated with cellular components
30 % is in the plasma ( ⅓ free form , ⅔ esterfied )


Transported by HDL and LDL
4

Fatty acids are short to long carbon chained
molecules
 Saturated fatty acids
 Unsaturated fatty acids

Phospholipids



Important components of cell membranes
Lecithin and sphingomyelin are utilized to determine
fetal lung maturity from amniotic fluid ( L / S Ratio )
Glycolipids


Lipids with a carbohydrate component
ABO antigen are glycolipids
LIPOPROTEINS
Lipoprotein is a complex spherical structure
that has a hydrophobic core wrapped in
hydrophilic coating.
4 major classes of lipoproteins.
Chylomicrons
Very low density lipoproteins (VLDL)
Low density lipoproteins (LDL)
High density lipoproteins (HDL)
LIPOPROTEINS COMPOSITIONS
COMPOSITION OF LIPOPROTEINS
Class
Diameter
(nm)
% protein
%
triacylglycerol
% cholesterol % phospholipid
& cholesterol
ester
HDL
5–15
33
30
29
4
LDL
18–28
25
50
21
8
IDL
25–50
18
29
22
31
VLDL
30–80
10
22
18
50
8
7
84
Chylomicrons 100-1000 <2
CHYLOMICRON STRUCTURE
LDL
Most core lipid in LDL is cholesterol ester.
ApoB100 is only apolipoprotein in the surface.
LDL RECEPTOR

Also named as apoB-100/apoE receptors

LDL receptors exist in the liver and in most peripheral tissues

The complexes of LDL and receptor are taken into the cells by
endocytosis, where LDL is degraded but the receptors are recycled

Number and function of the receptor shows LDL levels.

LDL cholesterol levels are positively related to risk of
cardiovascular disease

Therefore, cholesterol in LDL has been called “bad cholesterol”
APOLIPROPROTEINS
 Outer
protein “shell” of the lipoprotein molecule
 The protein – lipid interaction allows the water
insoluble lipid to become soluble in plasma
12
CLASSES OF APOLIPOPROTEINS

A, B, C, D, E are major classes
Subclasses: apo A-1, apo C-II
N.B. function of all apolipoproteins are not yet known
•
Act as structural components of lipoproteins
•
Recognize the lipoprotein receptors on cell membrane
surface as ligand
•
Activate/inhibit enzymes involved in lipoprotein
metabolism

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METABOLISM
Exogenous
 Endogenous


Lipoprotein lipase
 release
VLDL

FFA and glycerol from chylomicron and
Lecithin Cholesterol acyl transferase
LCAT
 Forms
cholesteryl esters from free cholesterol
and fatty acids
LIPID AND LIPOPROTEIN POPULATION
DISTRIBUTIONS
Serum lipoprotein concentrations differ
between adult men and women,
 Primarily as a result of differences in sex
hormone levels,



Women having, on average, higher HDL cholesterol
levels and lower total cholesterol and triglyceride
levels than men.
The difference in total cholesterol,
however, disappears after menopause as
estrogen decreases
HYPERCHOLESTEROLEMIA

Familial hypercholesterolemia (FH)
(7.5- 12 mmol/L)
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1
8
Primarily LDL elevations
Synthesis may be normal but decrease or lack LDL
receptors due to mutation in LDL receptor gene.
Therefore LDL builds-up in serum
Since cells cannot acquire from LDL therefore
increase internal synthesis of cholesterol.
Tendon xanthomatas
Early occurrence of coronary artery disease
HYPERTRIGLYCERIDEMIA

Triglycerides


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Familial hypertriglyceridemia


Genetic
Secondary hypertriglyceridemia


1
9
Borderline = 150-200 mg/ dl
High 200-500 mg/dl
Very High > 500 mg/dl
Hormonal imbalances
Imbalance between synthesis and clearance of VLDL
HYPERTRIGLYCERIDEMIA
Generally caused by deficiency of LPL or
LPL cofactor. (LPL hydrolyzes triglycerides
in chylomicrons and VLDL)
 Deficiency prevents processing and
clearing of triglycerides
 Elevated even with fasting

2
0
FAMILIAL COMBINED HYPERLIPIDEMIA
Presence of elevated levels of serum total
cholesterol and triglycerides
 Hepatic overproduction of apo B
 Increased VLDL and LDL

2
1
FAMILIAL HYPERCHYLOMICRONEMIA
Genetic mutation of LPL or apo C-II gene
 Recurrent abdominal pain
 Pancreatitis

CLINICAL DISORDERS OF LIPID METABOLISM
Primary
 Secondary

HYPERLIPIDEMIAS
SECONDARY
Disease
Lipid abnormality
DM
TG
Alcohol
TG
CRF
TG
Drugs thiazide
TG
Hypothyroidism
Cholesterol
Nephrotic syndrome
Cholesterol