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Flashcards in Metabolism - Fatty Acids Deck (43):

What are the classes of fatty acids?

1). Fatty acid derivatives
-->Fatty acids

2). HMG acid derivatives
-->Ketone bodies

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


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

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.


How are fatty acids released from adipose tissue?

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.


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

By hormone sensitive lipase.

- phosphorylation by glucagon and adrenaline = activated.

- dephosphorylated by insulin = inhibition.


How do released fatty acids enter the mitochondrial matrix?

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.


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

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


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

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.


What does beta oxidation of fatty acids produce?

Acetyl CoA and lots of NADH/FAD2H.


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

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.


How and where is glycerol metabolised?

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.


What are the 3 ketone bodies found in humans?



Where are ketone bodies formed?

In the mitochondria of the liver.


In what pathway are ketone bodies produced?

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


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

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

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


How is the production of ketone bodies alone regulated?

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.


How can acetoacetate be fed into the Krebs cycle?

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


How is glucose conserved when ketone bodies are forming?

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


How are some tissues dependant on glucose?

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.


Where does fatty acid synthesis occur?

The cytoplasm of liver cells.


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

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.


How is the fatty acid synthesised in liver cytoplasm?

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.


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

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


Where is cholesterol made and what are its functions?

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.


What are the features of cholesterolester?

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


What is a phospholipid and its features?

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


How big are lipoproteins?



What are lipoproteins constructed of?

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


What are the four lipoprotein types, in density order?



What are the proteins in lipoproteins and their function?

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.


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

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.


When and where are chylomicrons released?

They are released 4-6 hours after a meal into the lacteals
Lacteals-->lymphatic system -->thoracic duct-->left subclavian vein.


Where are VLDLs formed and what is their function?

Formed in the liver as an energy store (rich in TAGs).
Transport lipid from the liver into adipose tissue.


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

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.


Where are HDLs formed and what is their function?

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


How is HDL loaded with cholesterol?

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.


How are TAGs released from VLDLs and chylomicrons?

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.


How is cholesterol released from LDLs?

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.


What do cells do if they require more cholesterol?

They increase expression of ApoB100 receptors on their surface.


Why are LDLs bad?

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.


What is hyperlipoprotonaemia and its symptoms?

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.


What can cause hyperlipoprotonaemia?

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


How do you treat hyperlipoprotonaemia?

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.


What is LCAT and its function?

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.