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Lipoprotein Metabolism

Lipoproteins are complex lipids that facilitate lipid transport in the body, classified based on density into categories such as chylomicrons, VLDL, LDL, and HDL. Each type has a specific function, with LDL often referred to as 'bad cholesterol' due to its association with cardiovascular diseases, while HDL is considered 'good cholesterol' for its role in reverse cholesterol transport. A lipid profile is used to assess cardiovascular disease risk, with management strategies including dietary changes, exercise, and hypolipidemic drugs if necessary.

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11 views59 pages

Lipoprotein Metabolism

Lipoproteins are complex lipids that facilitate lipid transport in the body, classified based on density into categories such as chylomicrons, VLDL, LDL, and HDL. Each type has a specific function, with LDL often referred to as 'bad cholesterol' due to its association with cardiovascular diseases, while HDL is considered 'good cholesterol' for its role in reverse cholesterol transport. A lipid profile is used to assess cardiovascular disease risk, with management strategies including dietary changes, exercise, and hypolipidemic drugs if necessary.

Uploaded by

nikethhebron26
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Lipoprotein

metabolism
Lipoproteins
•Def: complex lipids
consisting of lipids &
proteins, involved in
lipid transport between
different organs.
Protein part is called
apoprotein /
apolipoprotein
Classification
Based on: Density
1.Chylomicrons
2. Very low density lipoproteins (VLDL)
3. Intermediate density lipoproteins (IDL)
4. Low density lipoproteins (LDL)
5. High density lipoproteins (HDL)
Structure
• Have a polar periphery made of
- Proteins
- Polar heads of PL &
- Cholesterol
Core consists of hydrophobic
lipids
- TG
- Tails of PL &
- Cholesterylester
Lipoprotein Structure

LDL
Apo-lipoproteins
• Protein part of lipoprotein
• All organs produce small
quantities but mainly
synthesized in LIVER &
apo B-48 in intestine
Chylomicrons
Synthesis
• in intestinal mucosal cells
as nascent CM

• Secreted into lacteals of


lymphatic system
Metabolism
(exogenous pathway)

Site – Adipose tissue, heart &


Sk.muscle

Enzyme: lipoprotein lipase (LPL) in


capillary endothelium of above
tissues
• Glycerol to liver for
gluconeogenesis / TG synthesis

• TG content of CM ↓
• CM remnant to liver by
receptor mediated endocytosis
CM- Function
1. Transports dietary TG
from intestine to
- Adipose tissue for
storage &
- Muscle & heart for their
energy needs
2. transports dietary
cholesterol & fat
soluble vitamins to
liver
Very low density lipoproteins
(VLDL)
Synthesis
• In liver : endogenous TG &
cholesterol +
- Apo B-100 - nascent VLDL
- Apo C-II & apo E (from HDL
in plasma)
Metabolism
(endogenous pathway)
•Site – Adipose tissue,
heart & Sk.muscle
•Enzyme: lipoprotein
lipase (LPL)
(capillary endothelium of
above tissues)
• FA to muscle & adipose
tissue
• Glycerol to liver for
gluconeogenesis / TG
synthesis

• This remnant is called


Intermediate density
lipoprotein (IDL)
• IDL returns apo C-II & apo E to
HDL & gets converted to LDL

• This conversion of
• VLDL IDL LDL is called
lipoprotein cascade
pathway
VLDL - Function

- Carries endogenous TG
from liver to peripheral
tissues -Adipose tissue
for storage &
- Muscle & heart for
energy
Low density lipoproteins
(LDL)

• Formed from VLDL in blood

• Cholesterol rich & contain


only apo B-100
Tissue uptake of cholesterol

LDL receptors Scavenger


receptors
-Almost all cells - macrophages
derived
from
monocytes
- Regulated - Unregulated
• Clinical significance:
• Defective LDL receptors -
familial
hypercholesterolemia
(FHC) – Type II A
LDL - Function
• Transports cholesterol
from LIVER to
PERIPHERAL TISSUES
• LDL has 75% of plasma
cholesterol
Clinical significance - LDL
• When LDL conc. in blood increases
a.Excess deposition of cholesterol in
tissues
b.Vascular diseases
c.Atherosclerotic lesions in coronary
arteries – myocardial infarction (MI)
& cerebral vessels - stroke
So LDL –cholesterol is “bad
cholesterol”
High Density Lipoprotein
(HDL)

• HDL is synthesized & secreted


from liver & intestine.
• Nascent HDL discoidal
• Consists of
- PL
- FREE cholesterol &
- apo A-I, C & E
Liver Intestine
(nascent
discoidal HDL)
PL,apo A1, C,E
SR-B1 cholesterol from
peripheral
tissues via
ABC protein

Spherical HDL
LCAT
C

CE

excretion of
cholesterol & bile acids
• ABC protein - ATP-Binding
Cassette Transporter -1

• Mature HDL spheres bind to


hepatic HDL receptors
Functions - HDL
1. Involved in reverse cholesterol
transport - Transports cholesterol
from PERIPHERAL TISSUES to LIVER,
which is later excreted through bile.
(The only excretory route of
cholesterol is through BILE)

2. HDL acts as a repository for apo C


& apo E required for the
metabolism of CM & VLDL
Clinical significance - HDL
• HDL level in serum is inversely
related to incidence of
myocardial infarction – (>
60mg/dl is cardioprotective &
anti-atherogenic)
hence “good
cholesterol”
Lipoprotein (a) / Lp(a)

•Lp(a) is associated with


heart attacks at younger
age (30-40 yrs)
Lipid Profile
• Def: estimation of
- Total cholesterol
- HDL-cholesterol LP
- LDL-cholesterol
- TG
in plasma using fasting blood sample
(8 -12 hrs fasting)

d
Purpose : to assess the risk
for cardiovascular disease
(Note: in addition to lipid
profile,
- Homocysteine
- High sensitivity C Reactive
protein (hs-CRP)
are estimated)
Indications
•
1. Suspected
- cardio vascular disease
- Coronary artery disease
- Peripheral vascular disease

2. All DM patients (once in 6


months)
3. Thyroid, liver & renal disease
4. All above 40yrs (once a year)
Lipid Profile – normal values
(mg/dl)
Lipid fraction

Total cholesterol 150-200

LDL cholesterol 70-130

HDL cholesterol >60

Triglyceride 50-150
• High levels of plasma
lipid profile indicates
risk for cardiovascular
disease.
Atherosclerosis
(athero-fatty, sclerosis- hardening)

Def: condition where plaques are


formed in vessel walls
constricting the lumen &
decreasing its elasticity
Stages :
- Chronic hypercholesterolemia
- ↑ formation of oxidized LDL
- Adhesion of blood monocytes to
endothelium
• nonspecific uptake of oxidized LDL
- foam cells

• Release of various growth


factors by macrophages

• Migration of smooth muscle cells


from media to intima & they
proliferate there.
• Cell death – calcification

• Fibrous plaque protrudes into


the lumen - narrowing of vessel
wall

• Blood flow through narrow lumen


is more turbulent & tendency for
clot formation ↑.
Atherosclerotic Plaque
Thrombosis of

Coronary cerebral vessel

ischemia (reduced delivery of


nutrients & O2 to tissues) &
infarction (death of tissue)

myocardial infarction
Stroke
Atherosclerosis – risk factors
1. High serum cholesterol – Conditions that ↑
cholesterol:
- DM –
- Obstructive jaundice –
- - Hypothyroidism –
- - Nephrotic syndrome –
- - Familial hyperlipoproteinemias
Hypertension
Obesity & sedentary life style
Cigarette – smoking ↑ oxdn of LDL &
↓ HDL
Management

Diet
Exercise Hypolipidemic
drugs
Management
1. ↓ dietary cholesterol - Eggs &
meat rich in cholesterol
2. ↑ PUFA & omega 3 FA –
vegetable oils & fish oil contain
PUFA – for esterification & final
excretion of cholesterol.
ω -3 Fas ↓ LDL.
3. ↑Green leafy vegetables – high
fiber content, ↓ reabsorption of
bile salts.
If diet & exercise are not enough to reduce
cholesterol levels,

Hypolipidemic drugs –
HMG CoA reductase inhibitors – “statins”

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