Fatty Acid Biosynthesis

Question 1

When are fatty acids synthesized?

Answer 1

Whenever excess calories is ingested

- Major source of C for synthesis of fatty acids is dietary carbohydrate

Question 2

Which tissue are fatty acids synthesized?

Answer 2

Primarily in the liver

To a lesser extent in adipose tissue

Question 3

What happens when excess dietary carbohydrate is consumed?

Answer 3

Glucose is converted to acetyl CoA
Acetyl CoA provides the 2C unit that condense in a series of reactions on the fatty acid synthase complex, producing palmitate that is converted to other fatty acids

Question 4

Where is fatty acid synthase complex located?

Answer 4

In the cytosol (and therefore uses cytosolic acetyl-CoA)

Question 5

What site are fatty acids synthesized?

Answer 5

Cytosol

Question 6

What are the redox coenzymes involved in fatty acid synthesis?

Answer 6

NADP+/NADPH

Question 7

What site are fatty acids degraded?

Answer 7

Mitochondria

Question 8

What are the redox coenzymes involved in fatty acid degradation?

Answer 8

NAD+/NADH

Question 9

Fatty acid occurs in the cytosol and starts with Acetyl Co-A. What is the problem associated with that?

Answer 9

• Most acetyl CoA is produced in the mitochondria

- Acetyl CoA is unable to travel through the mitochondrial membrane

Question 10

Using mitochondrial derived Acetyl CoA in the cytosol

Answer 10

• Pyruvate produced in the cytosol then transferred to the mitochondria
• Pyruvate + pyruvate dehydrogenase –> Acetyl CoA
• Fatty acid (in the mitochondria) + beta oxidation –> acetyl CoA
• Acetyl CoA + oxaloacetate –> citrate
• Citrate crosses the mitochondrial membrane and enters the cytoplasm
• Citrate + ATP-citrate lyase –> acetyl CoA
• Or AA in the cytosol can be converted to acetyl coA

Question 11

What is the rate limiting step in fatty acid synthesis?

Answer 11

conversion of acetyl CoA to Malonyl CoA by acetyl carboxylase
Reaction is irreversible

Question 12

What is malonyl Co-A?

Answer 12

The immediate donor of the 2C units added to the growing fatty acid chain on the fatty acid synthase complex

Question 13

How is malonyl Co-A synthesized?

Answer 13

Acetyl Co-A carboxylase adds a carboxyl group to acetyl Co-A in the presence of ATP and biotin

Question 14

How is the rate limiting step of fatty acid synthesis regulated?
What stimulates it?
What inhibits it?

Answer 14

• It is less active when phosphorylated and more active when dephosphorylated.
• Insulin dephosphorylates it and therefore activates it
• Citrate stimulates it (feed forward regulation)
• Palmitoyl CoA inhibits it (feedback inhibition - product of the pathway inhibits it)

Question 15

Describe the fatty acid synthase complex

Answer 15

• It contains 2 identical subunits in a head to tail arrangement
• Each subunit has seven catalytic activities
• The Acyl Carrier Protein (ACP) segment contains a phosphopantetheine

Question 16

What is the prosthetic group in the ACP?

Answer 16

Phosphopantetheine

Question 17

What is the purpose of Phosphopantetheine

Answer 17

The thiol group on phosphopantetheine reacts with malonyl CoA to form a thioester during fatty acid synthesis

Question 18

What is the initial step in fatty acid biosynthesis?

Answer 18

• an acetyl moiety is transferred from acetyl Co-A to the ACP phosphopantetheine sulfhydryl group of one subunit
• The acetyl moiety is then transferred to the cysteinyl sulfhydryl group of the other subunit
• Malonyl moiety from malonyl-CoA then attaches to the ACP phosphopantetheine sulfhydryl group of first subunit
• The acetyl and malonyl moieties condense with the release of malonyl carboxyl group as CO2
• A 4C b-keto acyl chain is now attached to the ACP phosphopantetheinyl sulfhydryl group.

Question 19

What is the second step in fatty acid biosynthesis?

Answer 19

1. Reduction of the 4C keto group to an alcohol
2. Removal of water to form a double bond
3. Reduction of the double bond

Question 20

What is the net result of the second step in fatty acid biosynthesis?

Answer 20

The original acetyl group is elongated by 2C

Question 21

What provides the reducing equivalents for the reactions in the second step of fatty acid biosynthesis?

Answer 21

NADPH

Question 22

How many subunits does fatty acid synthase has?

Answer 22

2 identical subunits

Question 23

What two domains do fatty acid synthase have?

Answer 23

acyl carrier protein (ACP) domain - with a phosphophantetheine residue (P-SH)
Cysteinyl sulfhydryl group (Cys-SH)

Question 24

Describe the synthesis of palmitate on the fatty acid synthase complex

Answer 24

1. Acetyl moiety is transferred from acetyl-CoA to P-SH of one subunit & then to Cys-SH of the other subunit
2. The acetyl & malonyl moieties condenses and malonyl carboxyl group is released as CO2
3. Reduction of the 4C keto group to an alcohol
4. Removal of water to form a double bond
5. Reduction of the double bond

The C4 fatty acyl chain is transferred to Cys-SH and condenses with a malonyl group

Question 25

The fatty acid is a dimer, how does this affect the release of palmitate?

Answer 25

Bc it is a dimer, there are two active sites which function simultaneously and independently both releasing palmitate

Question 26

Where are fatty acids elongated?

Answer 26

In the ER

Question 27

How are FA elongated?

Answer 27

1. After synthesis on the fatty acid synthase complex, palmitate is activated, forming palmitoyl-CoA 2, Palmitoyl-CoA is elongated, two carbons at a time, by a series of reactions that occur in the ER 3. Malonyl-CoA serves as the donor of the two carbon units (NADPH providing the reducing equivalents) 4. The major elongation reaction that occurs in the body involves the conversion of palmitoyl CoA (C16) to stearyl-CoA (C18), involving a reduction step, removal of water and reduction of the double bond 5, Very long-chain fatty acids (C22 to C24) are also produced, particularly in the brain

Question 28

Where does desaturation of fatty acids occur?

Answer 28

In the ER

Question 29

What are required for desaturation of FA?

Answer 29

O2 NADH cytochrome b5

Question 30

What are the common desaturation reactions?

Answer 30

Palmitic acid to palmitoleic acid | Stearic acid to oleic acid

Question 31

Polyunsaturation

Answer 31

Slide 17

Question 32

Importance of linoleic acid

Answer 32

Slide 18 It is a precursor of arachidonic acid which is a precursor of prostaglandins Linoleic acid + elongation + desaturation (x2) --> arachidonic acid --> prostaglandins

Question 33

A molecule of palmitic acid, attached to carbon 1 of the glycerol moiety of a triacylglycerol, is ingested and digested. The fatty acid is stored in a fat cell and ultimately is oxidized to carbon dioxide and water in a muscle cell. Choose the molecular complex in the blood in which the palmitate residue is carried from the lumen of the gut to the surface of the gut epithelial cell. ``` A. VLDL B. Chylomicron C. Fatty acid–albumin complex D. Bile salt micelle #. LDL ```

Answer 33

Ch 33