Download Cholesterol Metabolism and CVS Function

Cholesterol Metabolism and CVS Function
Learning Objectives
By the end of this lecture the students should be able to understand:
• The functions of cholesterol
• Cholesterol synthesis and metabolism
• Cholesterol transport
• Cholesterol as a risk factor for cardiovascular disease
Cholesterol
• The major sterol compose of four fused rings and an eight-membered,
branched hydrocarbon chain
Functions of Cholesterol
• Necessary part of cell membranes
• Precursor molecule for steroid synthesis
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–
–
–
–
–
–
Aldosterone
Corticosteroids
Estrogens
Progesterone
Testosterone
Bile acid for digestion
Vitamin D
Sources of Cholesterol
Cholesterol
Synthesis
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•
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•
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Occurs in cytosol
Requires NADPH and ATP
Highly regulated
80 % in liver, ~10% intestine, ~5% skin
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for
cholesterol synthesis.
• HMG-CoA is also an intermediate on the pathway for synthesis of ketone
bodies from acetyl-CoA.
Formation of HMG CoA-Rate Limiting step
 HMG-CoA is formed by condensation of acetyl-CoA & acetoacetyl-
CoA, catalyzed by HMG-CoA Synthase.
 HMG-CoA Reductase catalyzes production of mevalonate from HMGCoA
O
H3C
H2O  O
H3C
C
CH2
C
SCoA
SCoA
HMG-CoA
Synthase
HSCoA
OH
O
O
C
acetoacetyl-CoA
acetyl-CoA

O
C
CH2
C
O
CH2
C
SCoA
CH3
hydroxymethylglutaryl-CoA
Regulation of Cholesterol Synthesis
Cholesterol Transport
• Chylomicrons:
– Chylomicrons transport triglycerides from intestine
• Very Low Density Lipoproteins (VLDL) and Intermediate Density
Lipoproteins (IDL) :
– VLDL produced in liver . Carry cholesterol and triglycerides
• Low Density Lipoproteins (LDL)
– LDL result from metabolism of VLDL and IDL and carry cholesterol.
LDL are important cause of heart disease
• High Density Lipoproteins(HDL)
– HDL is “good” cholesterol. It removes cholesterol and protects against
heart disease
Cholesterol
Transport
Hypercholestrolemia
Blood Cholesterol levels
• Total cholesterol
< 5.17 mmol/L = Good
5.17-6.19
= Borderline High
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•
•
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> 6.20
= High
LDL
< 2.58 mmol/L = Good
2.58-3.33 = Near Normal
3.34- 4.12 = Borderline High
4.13-4.88 = High
> 4.88
= Very High
Hypercholestrolemia
Hypercholestrolemia-Risk factor for
Atherosclerosis
Atherosclerosis
Hypercholesterolemia and Risk of Stroke
HDL-Cardio protective Lipoprotein
Management of Hypercholestrolemia
• Life style modifications
– Balanced diet
– Exercise
– Stress management
• Drug Therapy