Lipid transport

Question 1

Where are lipids transported

Answer 1

From the gut to the liver
From the liver to non-hepatic tissue including adipocytes
Non-hepatic tissue back to the liver

Question 2

How are free fatty acids formed

Answer 2

From triglycerides stored in adipose tissue

Question 3

How are free fatty acids transported and why

Answer 3

Circulates bound to protein as NA+ salt, particularly albumin
This is because unbound fatty acids would act as a detergent and cause physical damage to membranes

Question 4

What are the different lipoproteins

Answer 4

1. Chylomicrons
2. Very low density lipoproteins (VLDL)
3. Intermediate density lipoproteins (IDL)
4. Low density lipoproteins (LDL)
5. High density lipoproteins (HDL)

Question 5

Chylomicrons

Answer 5

Synthesised from dietary fats, very little protein content

apoproteins: B48, Apo C2, C3 and E

Question 6

Very low density lipoproteins

Answer 6

High triglyceride content

Apoproteins; B100, Apo C1, C2, C3 and E

Question 7

Intermediate density lipoproteins

Answer 7

Mixed content

Apoproteins; B100 and Apo E

Question 8

Low density lipoproteins

Answer 8

High cholesterol content

Apoproteins; B100

Question 9

High density lipoproteins

Answer 9

High protein content

Apoproteins; Apo A1, A2, C1, C3, D and E

Question 10

What is the general layout of a lipoprotein

Answer 10

Each one has a very a large protein, an apolipoprotein
Cholesterol esters and triglycerides inside
Phospholipids and cholesterol on the outside

Question 11

Apoprotein fuction

Answer 11

Structural backbone of lipoprotein
Helps in the assembly of the lipoprotein around
Allows the lipids to be soluble and transported readily
Acts as enzymes or enzyme co-factors e.g. Apo C2 for lipoprotein lipase
Allows for tissue targeting e.g. Apo E binds to the HDL receptor

Question 12

Formation of chylomicrons

Answer 12

1. In the lumen of the gut, under the influence of lipases, triglycerides are broken down into FFA and monoacyl-glycerol
2. Transported into the mucosal cell and reformed back into triglycerides
3. Form with apoproteins to make chylomicrons and are secreted into the lymphatic system
4. Drains into the thoracic duct and goes into the vena cava
5. This takes them to the non-hepatic tissue first
6. Originally a nascent chylomicron
7. As it circulates it will interact with HDLs, and there will be an exchange of other apoproteins to form mature chylomicrons

Question 13

Chylomicron composition

Answer 13

Reflects meal composition
Low density due to high TG content
Contain fat soluble vitamins like A and E that prevent lipids from undergoing oxidation

Question 14

Why does the density of chylomicrons decrease over time and how

Answer 14

The triglyceride content will decrease since they will be acted upon by lipoprotein lipases that are expressed on endothelial cells that line blood vessels
Muscle and adipose tissue will have more of these enzymes
Chylomicron remnants will form, these are removed by the liver by binding to specific receptors on the liver causing endocytosis
Contents is recycled

Question 15

Lipoprotein lipase enzyme (LPL) action

Answer 15

Apo C2 will bind to LPL activating it

This enzyme will break down triglycerides into monoacyl-glycerol and FFA

Question 16

What is the differences in Km of the LPL isoforms between adipocytes and muscle

Answer 16

Km of LPL isoform in adipocytes is greater then the Km in muscle, therefore the muscle is normally saturated at low levels of lipoproteins
This means the adipocytes will act as a pool when circulating chylomicron concentrations are high

Question 17

LPL stimulation

Answer 17

LPL on adipocytes are stimulated by insulin

Question 18

where is VLDL synthesised

Answer 18

The golgi and the liver ER

Question 19

How do VLDL’s mature

Answer 19

They are released into circulation in a nascent form with B100, but then they interact with HDLs and exchange components
They gain Apo E and Apo C2 to become mature

Question 20

How is VLDL formation enhanced

Answer 20

1. Dietary carbohydrate
2. Circulating FFA
3. Alcohol and raised insulin and decreased glucagon

Question 21

VLDL’s have 2 fates

Answer 21

1. Returned to the liver

2. May form intermediate density lipoproteins

Question 22

LDL use

Answer 22

Carry cholesterol to the periphery and regulate de novo synthesis

Question 23

How are LDL’s metabolised

Answer 23

They contain 1 Apo B100, which can bind to a specific receptor on hepatocytes
They are either removed by the liver or removed by non-hepatic tissue for steroid biosynthesis

Question 24

What do HDL’s act as

Answer 24

They are circulating reservoirs of apoproteins C2 and Apo E

Question 25

Where are HDL’s formed

Answer 25

Formed mainly in the liver but can also be budded off LDLs and made from free Apo A1

Question 26

What is the HDL’s primary job and how does it carry it out

Answer 26

To remove cholesterol from circulation in plasma
They contain the enzyme LCAT, which esterifies the cholesterol preventing it from diffusing out the HDL
They take up cholesterol by reverse cholesterol transport
Endothelial cells have transporters that moves cholesterol from inside to outside using ATP, the HDL binds to this and removes the cholesterol

Question 27

How are HDL’s metabolised

Answer 27

HDL’s are transported to the liver and steroid producing cells
In the liver they are metabolised; the protein content is broken down by lysosomes and the components of that are incorporated into new proteins
The lipids will be used for ketone synthesis and the generation of glucose from the carbohydrate backbones

Question 28

How do HDL’s interact with other lipoproteins

Answer 28

They transfer cholesterol to VLDL’s and LDL’s using cholesterol ester transfer protein

Question 29

How can the HDL/LDL ratio be used

Answer 29

Can be used diagnostically to assess susceptibility to heart disease
Normal ratio is 3:5

Question 30

How are lipoproteins removed from circulation

Answer 30

Through receptor mediated endocytosis

LDL receptors will bind to both APO B100 and Apo E

Question 31

What are scavenger receptors

Answer 31

Expressed primarily on macrophages and endothelial cells

They aren’t regulated and normally only bind at high concentrations

Question 32

How are LDLs metabolised

Answer 32

1. LDL will bind to LDL receptors
2. These receptors are concentrated in coated pits
3. Clatherin protein association will aid in the membrane pinching off forming an endosome
4. These endosomes will start the process of breaking down the receptor-LDL interaction
5. The receptor will break off in vesicles and be recycled back to the surface membrane
6. The remaining LDL will be broken down when a lysosome fuses containing hydrolyses
7. Cholesterol esters will be converted to cholesterol which will diffuse out into the cytoplasm where they will be immediately re-esterified
8. The free cholesterol ester droplets will be resynthesised
9. The TG will be broken down into fatty acids which can be other metabolised
10. The amino acids will also be broken down

Question 33

How is LDL metabolism regulated

Answer 33

It is regulated by the intracellular concentration of cholesterol
At high concentrations of cholesterol the receptors will be less expressed on the membrane
Increased cholesterol will inhibit HMG-CoA reductase activity which will reduce LDL receptor expression

Question 34

What is familial hypercholesterolemia

Answer 34

A loss of LDL receptor function
Caused by a single amino acid substitution that prevents localisation of the LDL receptor to the coated pits
Symptoms; high serum cholesterol, developed blocked arteries, die young from heart attacks, de novo synthesis is not regulated by LDL

Question 35

How are lipoproteins regulated

Answer 35

Hormones; Insulin, thyroid hormones and cortisol

Nutritional status; decreased synthesis during fasting, increased by dietary fats