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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1

Where does fatty acid synthesis take place?

The cytosol

2

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

3

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

4

What is the first enzyme of of fatty acid synthesis?

Acetyl-CoA Carboxylase (ACC)

5

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

6

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

7

What are the hormonal regulation of ACC?

Insulin activates ACC (leads to weight gain)

Glucagon and epi inhibits ACC activation

8

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

9

What is the role of fatty acid synthase?

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

10

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

11

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

12

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

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

13

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

14

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

15

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

16

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

17

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

18

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

19

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

20

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

The acetyl-CoA can be converted to ketone bodies

21

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

22

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))

23

What gives off the sweet smell characteristic?

Acetone when produced in smaller quantities than the other ketones

24

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

25

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

26

Where do the reactions of keytone bodies take place?

In the mitochondrial matrix of the liver

27

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

Its the key regulatory enzyme for ketogenesis

28

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

29

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

30

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)