Lecture 1 - Chylomicrons

Question 1

Give 6 examples of cardiovascular diseases (CVD)

Answer 1

Coronary heart disease (CHD)

Myocardial infarction

Angina - coronary artery disease

Ischamic stroke - 1/4 of all CVD fat derived bloacked arteries to the brain

Atherosclerosis - blockage in arteries

Thromboembolism - clot

Question 2

What are factors linked to heart disease?

Answer 2

High blood levels of cholesterol

High blood levels of triglycerides
-Diet 60-130g/day, 90% absorbed

Question 3

What are the 2 sources of cholesterol?

Answer 3

Diet - 300mg/day, 30-60% efficiency and same amount secreted in bile

De Novo synthesis - 650-950mg/day in liver

Total : 1-1.5g/day in 70kg male for membrane and steroid hormone synthesis

Question 4

From where and to cholesterol is transported in the body?

Answer 4

Forward: Liver to peripheral tissue

Reverse: Peripheral tissue to liver

Question 5

What is the problem associated with transportation of lipids and how is this overcome?

Answer 5

Problem : Lipids are hydrophobic

Solution: Non-covalent associated with proteins in plasma or serum i.e Lipoproteins/Chylomicrons

Question 6

What are lipoproteins classified by, give examples?

Answer 6

Density of protein:lipid ratio

Classes:
VHDL (very little amounts)
HDL (2 classes)
IDL
LDL
VLDL

Question 7

Outline the components of lipoprotein

Answer 7

Outer: Polar protein phospholipid (PPL), apoproteins (CBA66:22:12) and cholesterol

Inner: lipid components - TAG(95%) and CE (5%)

Water insoluble, spherical globules

Question 8

What is the role of chylomicrons?

Answer 8

Deliver cholestero ester (CE) and Triacylglycerides (TAG) from gut to liver.

Forward transport of cholesterol

Question 9

Which lipoprotein has a strong INVERSE relationship with CHD development?

Answer 9

HDL

Highest ratio protein:lipid = 1:1

Question 10

Which lipoprotein is the major carrier of cholesterol (60%) and apoprotein (90%)?

Answer 10

LDL

Question 11

Whici lipoprotein constains free esterified cholesterol?

Answer 11

VLDL

Question 12

What is the TAG:CE ratio of LDL and HDL?

Answer 12

20% : 80%

TAG : CE

Question 13

How are chylomicrons made?

Answer 13

Nascent chylomicron formed in intestine (Golgi)

Secreted during absorption of dietary fats (TAG)

Size related to amount of fat intake

Production continued post-absorptive state

FFA + MAG > TAG in mucosal cell > Chylomicrons

Question 14

What is the role of coenzyme A-O-acyltransferase (ACAT)?

Answer 14

Conversion of cholesterol to cholesterol ester

Question 15

What are the apoproteins of chylomicron?

Answer 15

Synthesised in mucosal cells and essential:
Apo B48, A3, A4

Post-transcriptionally modified:
Apo B100
-CAA becomes UAA
-2153 glu becomes terminal codon truncated 2152 amino acid protein

Question 16

What happens to Apo ACE on plasma chylomicrons

Answer 16

Apo A dissociates from chylomicron

Apo C and E dissociate from HDL and bind to chylomicron

Apo CII - essential for binding to endothelial cells

Once chylomicrons have entered blood plasma, apo C will dissociate and re-bind to HDL

Question 17

What are chylomicrons digested by?

Answer 17

Lipoprotein lipase bound via. proteoglycan

Rate of hydrolysis depends on number of Apo CII (up to 12)

Question 18

How are lipoprotein lipase (LPL) synthesised?

Answer 18

By parenchymal cells of tissue and secreted for transplant to capillary endothelium.

Lipoprotein lipase is bound to polysaccharide chains to the endothelial cells

It has a rapid turnover (half life few hours)

Question 19

What promotes synthesis of lipoprotein lipase (LPL)?

Answer 19

Insulin

Synthesis occurs in adipose tissue

Question 20

How much TAG do chylomicrons retain after entering blood plasma?

Answer 20

20% TAG
100% CE

These are called chylomicron remnants
These are transported to liver

Question 21

How much TAG can be hydrolyzed daily?

Answer 21

300g

less than 1% detected in blood at any one time

less than 10 min for TAG, shorter for remnant residence times

Question 22

What is Abetalipoproteinemia?

Answer 22

clinical disorder associated with chylomicrons
-Genetic disorder (autosomal recessive)

cannot synthesise ApoB, therefore cannot make chylomicrons or LDL

Results in fats and fat soluble vitamins not absorbed in diet
and steatorrhea (frothy foul smelling and floating stool due to high fat content)

Question 23

What is hyperlipoproteinemia?

Answer 23

clinical disorder associated with chylomicrons
Lipoprotein lipase deficiency

Results in hyperchylomicronemia (overproduction of chylomicrons) when person is on normal diet. Treated by fat-free diet.

Causes
deficiency of LPL (type1)
production of abnormal LDL (type2)
apoC-II deficiency

Question 24

What is diabetes mellitus (typeI)?

Answer 24

clinical disorder associated with chylomicrons
autoimmune destruction of insulin producing cells

Has a secondary effect on LPL synthesis

Results in hyperlipoproteinemia