Fatty Acid Synthesis Week 2

Question 1

Where do we start numbering of fatty acid chains

Answer 1

Start at the COOH group and last is methyl group

NOrmamly we make a completely saturated palmitic Acid (16 chain)

Name number of chains: how many double bonds (at what position)

Question 2

What is a kink in a carbon chain? When is it important?

Answer 2

It’s a double bond (unsaturaton) imporatant that one side of a membrane is unsaturated because that adds fluidity

Question 3

List the groups of fatty acids

Answer 3

Short chain FA- 2-4

Medcium Chain- 6-10

Long Chain- 12-18

Very long chain 20-24

We make mostly long chains., but remember that short and medium are good for babies.

Question 4

What is special about breast milk

Answer 4

It is only short and medium fatty acids so it can go directly to portal blood and don’t need carnitine to go into the mitochondria. Also has essential fatty acids. Has glucose (not sucrose) so easy transport. Has essential vitamins, minerals and anitbodies.

Question 5

How do we make aclyglycerols

Answer 5

we esterify fatty acids and glycerol and we store it.

Question 6

Where is most fatty acid made? Where else

Answer 6

LIver cytosol!!!

SOme in mammary glands and adipose

Question 7

What is the starting chain that other FA are modified from

Answer 7

Palmitic acid which is a 16 chain carbon

Question 8

What’s the source of all carbons and where is it produced from?

Answer 8

Acetyl CoA (C2) and it is produced from glucose and some AA. It has to be transported to the mitochondria for FA synthesis.

Question 9

When we start with Acetyl CoA in the fatty acid snythesis process what enzymes adds to it?

Answer 9

Two carbons are added to the carboxyl end by fatty acid snythase

The rest of the two carbon are added in the form of malonyl-CoA which are produced from Acetyl CoA by Acetyl Coa-carboxylase.

Question 10

Explain process of getting Acetyl-CoA to where it needs to be for FA synthesis

Answer 10

Fatty acid synthesis takes place in thecytosol, but AcetylCoA is a source of the PDH reaction which takes place in the mitochondria.

Since AcetylCoA can’t leave the mitochondria, a process involving citrate moves the C2 unit out. (Aectyl CoA + OAA –citrate synthase–> citrate)

Citrate can leave the mitochondria easily and with one ATP and ATP-citrate lyase can be cleaved and release Acetyl CoA and Oxalacetate.

Question 11

CItrate brings out Acetyl CoA and ?? What happens to the ???

Answer 11

Oxaloacetate (OOA) is reduced to malate by one NADH. THe malate is the decaroxylated by the NADP-linked malic enzyme to produce NADPH, pyruvate and CO2. The pyruvate goes back to the mitochondria.

Question 12

Transfering Acetyl CoA to cytosol cost what? Produces what?

Answer 12

Cost NADH and Atp

Produces NADPH

Since Acetyl CoA can’t leave we send out citrate which breaks down to OAA and AcetylCoA- COST ONE ATP

OAA to Malate through Malate DH- COST ONE NADH

Malate to pyruvate through Malic Acid- MAKES ONE NADPH

Question 13

The formation of palmitate cost how many NADPH?Where do they come from?

Answer 13

Cost 14 NADPH

8acetyl CoA (2 carbon chain) go through the citrate cycle making 8NADPH

The other 6 come from PPP/hoexose monophosphate shunt

Question 14

What is the rate limiting step in FA synthesis? Whats the actual step?

Answer 14

Formation of Malonyl-CoA

Acetyl CoA +HCO3- +ATP—Acetyl-CoA Carboxylase-> Malonyl-CoA + H2O + ADP +Pi

Acetyl Coa carboxylase requires coenzyme Biotin

Question 15

Alloseric regulation of Acetyl CoA Carboxylase

Answer 15

The enymze that takes Acetyl CoA to Manoyl Coa

1. Its inactive monoeric state, but when with citrate it active (postive)
2. Palmotoyl CoA inhibts it (Negative FEEDBACK)

Question 16

HOrmonal regulation of Acetyl CoA Carboxylase

Answer 16

The enzyme that takes Acetyl Coa to Manyl CoA (rate limiting in FA synthesis)

1. Controlled by cAMP phos/dephos pathway in which phos is less active– glucagon- phos, insulin dephos
2. Enzyme is synthesized more when insulin high and low fat diet
3. Glucagon, fasting (AMPK- kinase upredgulated when there is low cellular energy level), and high fat diet decrease enzyme expression

Question 17

Steps of FA synthesis

Answer 17

1. Start with Acetyl CoA (remember it leaves mitochondria as citrate then use ATP Citrate Lyase)
2. AcCoA binds to the multifunctional enzyme
3. 7- Malonyl CoA added one by one by fatty acid synthase
4. After adding maloynl CoA there is a reduction, then dehydration, then reduction– reductase use NADPH

5 Hydrolyze the enzyme off palmitate when we reach the 16 carbon chain

Question 18

Regulatoin of FA synthase

Answer 18

Alloesteric- activated by G6P (upstream from citrate)

Hormonal- Up-insulin Down- Glucagon

Question 19

What energy and components use in FA synthesis

Answer 19

7 ATP- one ATP is used in the formation of Malonyl-CoA (come from the 7AcetylCoA we use)

14 NADPH- 2 used for every elongation

Palmitate is 7Malonl CoA + 1 AcetylCoA

Question 20

What are the 3 further modifications of FA

Answer 20

Elongation, dessaturation and hydroxlation

Question 21

Explain what happens (where) in elongation of FA

Answer 21

They are elongated in the ER or mitochondria in a process similiar to the production in the cytosol with malonyl-CoA as the source, but the itnermediates are CoA esters and arn’t attached to a protein.

To 18carbon chain is almost exclusively in the ER.

Brain cells can synthesize long chains (20-24)

Question 22

Desaturationa and dehydroxylation of FA acis.

Answer 22

Mixed-function oxidases in the ER are responsible to introduce a variety of cisdouble bonds to fatty acids.

The enzymes use NADPH and oxygen.
 Linoleic and linolenic (ω-3 and ω-6) fatty acids cannot be prod

Question 23

How do we store FA? How are they synthesized?

Answer 23

We store them as triglycerols in the liver (in VLDL) and adipose (liquid droplets).

Synthezies from faccty actyl CoA and GLycerol 3-phosphate