Fatty acid synthesis, ketone bodies and cholesterol synthesis Flashcards Preview

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Flashcards in Fatty acid synthesis, ketone bodies and cholesterol synthesis Deck (55)
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Where does fatty acid synthesis take place?

The cytosol


In what state, high or low energy, does fatty acid synthesis take place?

It uses energy to construct the fatty acids during high energy states


What does insulin do in terms or up or down regulation of fatty acid synthesis?

It upregulates it and insulin initiation leads to weight gain


What is the first enzyme of of fatty acid synthesis?

Acetyl-CoA Carboxylase (ACC)


What is the role of Acetyl-CoA Carboxylase (ACC)?

Its the first enzyme and it used to convert acetyl-CoA into malonyl-CoA using bicarb

**it requires biotin (vit B7) as a prosthetic group


What are the allosteric regulation of ACC?

Citrate accumulation activates ACC (product from the TCA)

The end product of fatty acid synthesis palmitoyl-CoA inhibits ACC activation


What are the hormonal regulation of ACC?

Insulin activates ACC (leads to weight gain)

Glucagon and epi inhibits ACC activation


How are fatty acid synthesis and B-oxidation of fatty acid related?

They are inversely related - if one goes up the other will go down


What is the role of fatty acid synthase?

After malonyl-CoA production, its the enzyme that begins the cycle


What are the four steps that the fatty acid synthase follows?

1. Condensation
2. First reduction
3. Dehydration
4. Second Reduction

**different portions of the synthase handle these steps
****goes thro 7 cycles until palmitic acid (C16:0) is formed


What does each cycle in the FA synthase utilizes?

They all use malonyl-CoA to add twoo carbon units to the elongating fatty acid

****The first step does not use malonyl-CoA


What is the role of the acyl carrier protein (ACP)?

It is required to carry and bind malonyl CoA to fatty acid synthase


What is the energy usage of the fatty acid synthesis?

1 ATP required for the synthesis of malonyl-CoA
***7 ATP are needed for the synthesis of 1 molecule of palmitic acid

Each cycle of FA synthase requires 2 NADPH
***14 NADPH are needed for the synthesis of 1 palmitic acid

***The energy of ATP and NADPH is stored in the fatty acids


Where does the acetyl-CoA come from and how does it relate to where fatty acid synthesis takes place?

The acetyl-CoA comes from the mitochondria but it needs a way to exit because fatty acid synthesis takes place in the cytoplasm


What is the citrate transport system?

Is used to transport acetyl-CoA into the cytoplasm

**only the carbon skeleton is transported and once in the cytosol it binds to free CoA to form acetyl-CoA. (reverse of the TCA)

***HIGH energy state is coupled to FA synthesis, glycolysis is the supplier of NADH in the cytosol


What is the overall balance of fatty acid catabolism vs synthesis maintained by?

Insulin:glucagon ration (IGR)
*insulin turns sythesis on
**glucagon turns it off


What are the two enzymes that are key to the coordination of fatty acid metabolism?

1. Acetyl-CoA carboxylase (ACC)

2. Carnitine acyltransferase (CPT1) - this will limit transport of fatty acids into the mitochondrial matrix for B-oxidation


What happens when you take in a high carb meal and its effects on fatty acid metabolism?

1. triggers release of insulin
2. insulin activates ACC
3. ACC catalyzes the formation of malonyl-CoA
4. Malonyl-CoA inhibits CPT1, which stops CPT1 from bring fatty acids into the mitochondria (blocks B-oxidation)
5. Insulin also block LpL (which cuts fatty acids off adipose) by blocking it there is inhibition of fatty acid release


What happens when blood glucose levels drop?

1. Glucagon is released
2. This inactivates ACC
3. This leads to less malonyl-CoA
4. Less malonyl-CoA removes the suppression of CPT1
5. FAs enter the mitochondrial matrix and burn as fuel by B-oxidation
6. Glucagon will also trigger release of fatty acids from adipose tissue by activating LpL


What happens when glucose levels are low or when someone cant utilize glucose (diabetes) ?

The acetyl-CoA can be converted to ketone bodies


Where does ketogenesis take place?

Acetyl-CoA is formed in the liver by B-oxidation of fatty acids and it can be converted into keytone bodies


What are the three types of keytone bodies?

1. Acetone
2. Acetoacetate
3. D-B-Hydroxybutyrate (during unfed state (low glucose) or glucose intolerance (diabetes))


What gives off the sweet smell characteristic?

Acetone when produced in smaller quantities than the other ketones


What is the purpose keytone bodies in the body?

Acetoacetate and B-hydroxybutyrate are transported thro blood to other tissues this is used by the brain since glucose is low and FAs cant be transported

**brain uses the keytone bodies during prolonged starvation


What happens during diabetes when you have a high accumlation of ketones in the body?

When you cant use glucose it leads to keytones to accumulate in the body which leads to diabetic keto acidosis (DKA)
Acetoacetate and B-hydroxybutyrate are acidic


Where do the reactions of keytone bodies take place?

In the mitochondrial matrix of the liver


What is the role of HMG-CoA lyase in terms of regulation?

Its the key regulatory enzyme for ketogenesis


What are the steps of ketogenesis

Happens in liver
1. Two acetyl-CoA molecules are reacted to produce acetoacetyl-CoA
2. Acetoacetyl-CoA reacts with another acetyl-CoA to produce HMG-CoA
3. HMG-CoA breaks down acetoacetate and acetyl-CoA
4. The acetoacetate can then be either decarboxylated to acetone or be reduced to B-hydroxybutyrate


What is HMG-CoA synthase?

It catalyzes the production of acetoacetate from six-carbon compound HMG-coA

**takes acetoacetyl-CoA and combines an acetyl-CoA to it to create the HMG-CoA


What does the HMG-CoA lyase do?

It removes an acetyl-CoA from HMG-CoA to produce Acetoacetate (which then leads to acetone and d-B-hydroxybutyrate)