Metabolism - Fatty Acids

Question 0

How are fatty acids stored in the adipose from the gut?

Answer 0

1) . TAGs are broken down into fatty acids and glycerol by pancreatic lipases, then absorbed by the small intestine.
2) . FA and glycerol are recombined in the gut to give TAGs (using glycerol phosphate).
3) . TAGs are then transported via chylomicrons to the adipose tissue.

Question 1

What are the classes of fatty acids?

Answer 1

1) . Fatty acid derivatives
- ->Fatty acids
- ->TAGs
- ->Phospholipids

2) . HMG acid derivatives
- ->Cholesterol
- ->Ketone bodies

3) . Vitamins
- ->A, D, E, K

Question 2

How are fatty acids released from adipose tissue?

Answer 2

The adipose tissue contains a cycle, which needs glucose n order to keep TAGs stored.
When there in no glucose, this cycle can’t continue as fattyacylCoA can’t join with glucose to form TAGs. This means that fatty acids are then released.

Question 3

How is the release of fatty acids from adipose tissue controlled?

Answer 3

By hormone sensitive lipase.

• phosphorylation by glucagon and adrenaline = activated.
• dephosphorylated by insulin = inhibition.

Question 4

How do released fatty acids enter the mitochondrial matrix?

Answer 4

1). Fatty acyl CoA synthase and ATP are used to link the fatty acid to CoA = activation.
Now it is too big to cross the mitochondrial membrane.

2). Carnitine shuttle transfers it across the membrane using CAT1 to give acyl carnitine and CoA.

Question 5

How is the transport of fatty acids into the mitochondrial matrix controlled?

Answer 5

The transporter is inhibited by Malonyl CoA, the start substance 2C are added onto during fatty acid synthesis.

Question 6

What happens to fatty acids in the mitochondrial matrix to metabolise them?

Answer 6

1). The acyl cartinine is converted back to acylCoA using CAT2.

2) . Beta oxidation occurs…
- -> a number of reactions in which 2C atoms are removed from the fatty acid chain each time until the chain is 2C long.

Question 7

What does beta oxidation of fatty acids produce?

Answer 7

Acetyl CoA and lots of NADH/FAD2H.

Question 8

What happens in the metabolism of fatty acids when they are an odd number of carbon atoms long?

Answer 8

Carbon atoms are removed until the chain is 3C long. It is then carboxylated using ATP and carboxylase to give a 4C molecule that is rearranged by mutase and vitamin B12.

Question 9

How and where is glycerol metabolised?

Answer 9

Glycerol is converted to glycerol phosphate by glycerol kinase, which can then be converted into either TAG synthesis route, or into DHAP (which uses NADH) which can be fed into glycolysis at G3P
It uses ATP and occurs in the liver.

Question 10

What are the 3 ketone bodies found in humans?

Answer 10

Acetoactetate
Acetone
Beta-hydroxybuterate.

Question 11

Where are ketone bodies formed?

Answer 11

In the mitochondria of the liver.

Question 12

In what pathway are ketone bodies produced?

Answer 12

Acetyl CoA is converted to HMGCoA.

HMGCoA can be converted into melavonate, and then cholesterol using HMGCoA reductase, or into ketone bodies using lyase.

Question 13

How is the pathway in which ketone bodies and cholesterol are produced regulated?

Answer 13

High insulin to glucagon ratio inhibits lyase and stimulates HMGCoA reductase.

Low insulin to glucagon ratio stimulates lyase and inhibits HMGCoA reductase.

Question 14

How is the production of ketone bodies alone regulated?

Answer 14

If lots of FA are being produced, this forms a lot of acetyl CoA. This all feeds into krebs, forming a build up of citrate.
Citrate then can inhibit the enzyme isocitrate dehydrogenase, which stops Krebs, meaning the acetyl CoA needs feeding elsewhere = into production of ketone bodies.

Question 15

How can acetoacetate be fed into the Krebs cycle?

Answer 15

It takes a CoA from succinate in krebs to form acetyl CoA, and is therefore fed back into the cycle.

Question 16

How is glucose conserved when ketone bodies are forming?

Answer 16

The muscles will use ketone bodies whilst also breaking down to give amino acids for gluconeogenesis.
This conserves glucose for the brain.

Question 17

How are some tissues dependant on glucose?

Answer 17

The brain can only use glucose (will use ketone bodies at a push).
Some tissues need glucose for specialised function, such as the liver cells producing TAGs.
Some tissues have absolute requirement as uptake depends on the concentration of the blood, such as the RBCs as these don’t contain mitochondria so can’t respire.

Question 18

Where does fatty acid synthesis occur?

Answer 18

The cytoplasm of liver cells.

Question 19

How is acetyl CoA transported to the cytoplasm in fatty acid synthesis?

Answer 19

It is reacted with oxaloacetate to give citrate.

Citrate can the exit the mitochondria and convert back into Acetyl CoA and oxaloacetate once in the cytoplasm.

Question 20

How is the fatty acid synthesised in liver cytoplasm?

Answer 20

Acetyl CoA is converted into malonyl CoA using ATP and acetyl carboxylase in a regulated step.
2C is then added onto the malonyl CoA numerous times until it builds up, using NADPH, ATP and fatty acid synthase.
The fatty acid is then linked to ACP (acyl carrier protein) and transported in the blood.

Question 21

How is the conversion of acetyl CoA to malonyl CoA in fatty acid synthesis regulated?

Answer 21

It is performed by acetyl carboxylase.
It is activated by:
--> citrate - allosteric
--> insulin - dephosphorylation
It is inhibited by:
--> AMP - allosteric
--> glucagon/adrenaline - phosphorylation

Question 22

Where is cholesterol made and what are its functions?

Answer 22

Formed in the liver.
It can make steroid hormones and bile acids.
It forms a major part of the cell membrane.
Esterified by fatty acids to give cholesterolesters.

Question 23

What are the features of cholesterolester?

Answer 23

Esterification eliminates the only polar part of the cholesterol, so it becomes less water soluble.

Question 24

What is a phospholipid and its features?

Answer 24

It is a major component in cell membranes.
Formed from a diacylglycerol and phosphate group.
Form balls due to hydrophobic/hydrophilic parts.

Question 25

How big are lipoproteins?

Answer 25

5-100nm

Question 26

What are lipoproteins constructed of?

Answer 26

Polar molecules (phospholipids, protein, cholesterol) surrounding non polar, hydrophobic lipid particles (TAGs, cholesterolesters).

Question 27

What are the four lipoprotein types, in density order?

Answer 27

Highest-
HDL
LDL
VLDL
Chylomicron
Lowest-

Question 28

What are the proteins in lipoproteins and their function?

Answer 28

They are approve ins, specific to the type of lipoprotein they’re in.
They can occur in polymorphisms (ApoE especially).
They bind to cell surface receptors and cause activation of enzymes there.

Question 29

What is the function of chylomicrons and how are they formed?

Answer 29

They transfer TAGs from the diet to the adipose tissue mostly.
They are formed by enterocytes in the small intestine, which take up FA and glycerol, recombine them to form TAGs, then bind these to specific apoproteins in the lipoprotein.

Question 30

When and where are chylomicrons released?

Answer 30

They are released 4-6 hours after a meal into the lacteals

Lacteals–>lymphatic system –>thoracic duct–>left subclavian vein.

Question 31

Where are VLDLs formed and what is their function?

Answer 31

Formed in the liver as an energy store (rich in TAGs).

Transport lipid from the liver into adipose tissue.

Question 32

When and how are LDLs formed, and what is their function?

Answer 32

They are formed in the liver as this is where the cholesterol is synthesised and bound to apoproteins.
They transport cholesterol from the liver to the tissues.

Question 33

Where are HDLs formed and what is their function?

Answer 33

They’re formed in the tissues and transport cholesterol to the liver to be broken down.

Question 34

How is HDL loaded with cholesterol?

Answer 34

Nascent HDLs are synthesised in the liver or empty VLDL remnants are used.
These sequester cholesterol from the capillaries then mature into HDL particles and transport back to the liver.

Question 35

How are TAGs released from VLDLs and chylomicrons?

Answer 35

The chylomicrons/VLDLs containing the TAGs bind to lipoprotein lipase on the endothelial surface of capillaries.
This cleaves the TAGs into FA and glycerol.
The fatty acids enter the cell to undergo beta oxidation and the glycerol remains in circulation. VLDLs also leave behind remnants, which are recycled or removed by the liver.

Question 36

How is cholesterol released from LDLs?

Answer 36

The LDL binds to receptors on the surface of target cells which recognise ApoB100.
The LDL is taken into the cell by endocytosis where lysosomes break it down to release the cholesterol inside.
These cholesterol is linked to fatty acid = cholesterolester for storage.
The LDL shell is recycled.

Question 37

What do cells do if they require more cholesterol?

Answer 37

They increase expression of ApoB100 receptors on their surface.

Question 38

Why are LDLs bad?

Answer 38

They lead to atherosclerosis:
1). Cholesterol deposits in the intima of the capillary walls.
2). These are oxidised and then engulfed by macrophages.
3). The macrophages turn into foam cells which accumulate to give a visible fatty streak.
4). This fatty streak can expand to form an atheroma.
Atheroma can burst –> thrombosis –> blood clot.

Question 39

What is hyperlipoprotonaemia and its symptoms?

Answer 39

It is a raised level of one of the lipoprotein classes and therefore plasma TAG or cholesterol levels, after a fast of 12hours.

1) . Xanthelasma - fatty deposits of cholesterol under the skin.
2) . Xanthoma - lipid accumulation around the tendons.
3) . Corneal arcus - fat forms a white ring around the iris.

Question 40

What can cause hyperlipoprotonaemia?

Answer 40

1) . Damaged cell receptors.
2) . Defective enzyme.
3) . Variation in a dodgy apoprotein.

Question 41

How do you treat hyperlipoprotonaemia?

Answer 41

1) . Diet and lifestyle changes.
2) . Statins
- -> inhibit HMGCoA reductase = less cholesterol produced.
- -> increase LDL receptor expression = more up taken by cells = not in blood.

Question 42

What is LCAT and its function?

Answer 42

It helps to form and maintain lipoprotein structure as if the structure is changed (by becoming non spherical or having a dodgy surface lipid to core lipid ratio) it can become unstable.
This leads to failure of lipid transport = atherosclerosis and dodgy deposits.