22B Fatty Acid Synthesis

Question 1

Where does Fatty Acid Synthesis occur?

Answer 1

Cytoplasm

Question 2

What are Fatty Acids Synthesized from?

Answer 2

Acetyl CoA’s from the matrix of Mitochondria

Question 3

Activation of Acetyl CoA in Fatty Acid Synthesis

Answer 3

Addition of CO2 in the form of HCO3- (CO2 in aqueous solution dissociates into HCO3- and H+)

Question 4

Acetyl CoA Carboxylase

Answer 4

Carboxylation (addition of CO2)
Acetyl CoA + ATP + HCO3- -> Malonyl CoA + ADP

• Commited Step in Fatty Acid Synthesis=REGULATED
• Requires ATP
• Prosthetic Group=Biotin

Question 5

How is biotin attached to the enzyme Acetyl CoA Carboxylase

Answer 5

E amino group of Lysine

Question 6

What three enzymes has Biotin as Prosthetic group?

Answer 6

Acetyl CoA Carboxylase
Propionyl CoA Carboxylase
Pyruvate Carboxylase

Question 7

Acetyl Transacylase

Answer 7

Exchanges CoA for ACP on acetyl group forming Acetyl ACP

Acetyl CoA-> Acetyl ACP

Question 8

Malonyl Transacylase

Answer 8

Transfer malonyl group from CoA to ACP

Question 9

ACP

-structure

Answer 9

Acyl Carrier Protein

• 77 amino acids
• Acyl Group Attaches to serine R group ( same as Coenzyme A)

Question 10

Elongation Phase of Fatty Acid Synthesis:

-1st Step

Answer 10

Condensation
Acetyl ACP + Malonyl ACP -> AcetoAcetyl ACP + ACP + CO2

• catalyzed by Acyl-maloynl ACP condensing enzyme
• Decarboxylation reaction which provides the energy (decreases in free energy)

Question 11

Elongation Phase of Fatty Acid Synthesis:

-2nd Step

Answer 11

Reduction
AcetoAcetyl ACP-> D-3-hydroxybutryl ACP

catalyzed by B-Ketoacyl ACP reductase
NADPH is oxidized to NADP+

Question 12

Elongation Phase of Fatty Acid Synthesis:

-3rd Step

Answer 12

Dehydration
D-3-hydroxybutryl ACP (4C)-> Crotonyl ACP(4C) + H2O

catalyzed by 3-hydroxyacyl ACP dehydrates

Question 13

Elongation Phase of Fatty Acid Synthesis:

-4th Step

Answer 13

REduction
Crotonyl ACP (4C) -> Butyryl ACP

catalyzed by Enoyl ACP reductase
-NADPH oxidized to NADP+

Question 14

Acetyl CoA Carboxylase

-Structure

Answer 14

Contains all enzymes from elongation step
Dimer: 3 domains with 7 activites
1) Domain 1-substrate entry and condensation unit
-AT=acetyl transacylase
-MT-Malonyl Transacylase 
-CE= Acyl-Malonyl ACP condensing enzyme
2) Domain 2-reduction unit
-KR=B-ketoacyl ACP reductase
-DH=3-hydroxyacyl ACP dehydratase
-ER=Enoyl ACP reductase
3) Domain 3-palmitate release
-TE-Thioesterase

Question 15

Palmitate synthesis requires

Answer 15

8 Acetyl CoA
14 NADPH
7 ATP’s

Question 16

How Are acetyl CoA transported from Mitochondria to Cytoplasm for Fatty Acid Synthesis?

Answer 16

Acetyl CoA can’t cross the inter membrane of Mt
* When Acetyl CoA and OAA concentration is High, Citrate is synthesized and transported to cytoplasm for Fatty Acid Synthesis

Steps:

1) Acetyl CoA + OAA -> Citrate in Krebs cycle
2) Citrate transported across the inter membrane of mitochondria and through porons of the outer mitochondrial membrane into the cytoplasm
3) Citrate-> Acetyl CoA + OAA
- catalyzed by ATP citrate lipase
- occurs in cytoplasm
- acetyl CoA can now undergo Fatty Acid Synthesis
4) OAA -> Malate
- catalyzed by Malate Dehydrogenase
- OAA is reduced to Malate
- NADH is oxidized to NAD+ to be used in glycolysis and fermentation
5) Malate-> Pyruvate
- catalyzed by NADP+ linked malate enzyme
- oxidizes malate to pyruvate
- Synthesizes ONE NADPH per acetyl unit

Question 17

What is the source of NADPH in Fatty Acid Synthesis?

Answer 17

1) Oxidation of Malate to Pyruvate by NADP+ Linked malate enzyme
2) Pentose phosphate pathway

Question 18

Acetyl CoA Carboxylase Regulation

Answer 18

High Activity when: there is a high concentration of

• Carbohydrates concentration=represented by citrate
• High Energy Charge (ATP)

Turned ON:

1) dephosphorylation by Protein Phosphatase 2A
2) Allosterically by: Citrate which facilitates polymerization of dimers of Acetyl CoA carboxylase

Turned OFF:

1) Phosphorylation by AMP dependent Protein Kinase
- stimulated by AMP and Inhibited by ATP
2) Palmitoyl CoA
- faciliates depolymerization of Acetyl CoA carboxylase polymers
- Inhibits Citrate translocase
- Inhibits Glucose 6-Phosphate in Pentose Phosphate Pathway

Question 19

Hormonal Control of Acetyl CoA Carboxylase

Answer 19

Turns ON:
1) Insulin- well fed state
-activates Protein Phosphatase 2A which converts carboxylase into dephosphorylated form (Active form)
Turned OFF:
1) Glucagon and Epinephrine
-Maintains carboxylase in Phosphorylated State by AMP-dependent Protein Kinase

Question 20

Adaptive Control

Answer 20

1) regulation due to dietary changes
- Fasting animals then switch to high carbohydrate state (Fed state), low fat diets exhibit increase conc of Acetyl CoA Carboxylase and Fatty Acid Synthase

2) Transcriptional Level
- up regulate the synthesis of mRNA for the enzymes apart of Fatty Acid Synthesis

Question 21

Synthesis of >16 Carbon Fatty acids

Answer 21

Enzymes located on cytoplasmic side of smooth ER

Adds two carbon units to carboxyl end of saturated and unsaturated fatty acids from Malonyl CoA
-energy provided by decarboxylation of Malonyl CoA

Question 22

Synthesis of Unsaturated Fatty Acids

Answer 22

Enzymes located on cytoplasmic side of smooth ER
Double Bonds inserted by multi enzyme complex

1) NADH cytochrome b5 reductase
- FAD prosthetic group
2) cytochrome b5
- Heme prosthetic group with Iron
3) Desaturase
- Non heme iron
- Molecular O2 which accepts 4 electrons- 2 from NADH and 2 from single bond of fatty acyl substrate
- NADH provides 2 electrons

Question 23

Synthesis of Unsaturated Fatty Acids in Mammals

Answer 23

Mammals lack the enzyme to introduce double bonds at carbon atoms beyond C9:

Essential Fatty Acids-Linoleate and Linolenate both have double bonds after C9 this is why they are essential to mammals

Question 24

Arachidonate

Answer 24

20:4 Fatty acid is precursor for synthesis of Eicosanoid Hormones

Eicosanoid Hormones: contain 20 carbons

• Prostaglandins
• Prostacyclins
• Thromboxanes
• Leukotrienes