Lipid Metabolism I

Question 1

Purpose of Malonyl CoA?

Answer 1

RLS for FA synthesis!!!

• Inhibits Carnitine Acyltransferase
• Prevents the Synthesis and Degradation from occurring SIMULTANEOUSLY

Question 2

What is a precursor of FA synthesis?

Answer 2

Acetyl CoA

- 2C molecule

Question 3

Steps from Citrate to Pyruvate in the Cytosol

Answer 3

1. Citrate —> ACoA + OAA
   - by Citrate LYASE
2. OAA ——> Malate
   - by Malate Dehydrogenase
3. Malate ——> Pyruvate
   - by Malic enzyme

Question 4

The reactions of the FA synthesis occur on the ___?

Answer 4

FA synthase Complex

Question 5

How does Pyruvate ——> OAA?

Answer 5

It is CARBOXYLATED by Pyruvate Carboxylase

Question 6

What is the “Big Daddy” of the Regulation of ACoA Carboxylase?

Answer 6

Phosphorylation (-) and Dephosphorylation (+)

(+)
- Insulin via protein phosphatase

(-)
- Epinephrine
- Glucagon
     (Both by PKA)
- AMP via AMP Kinase

Question 7

What is the Reducing power of FA elongation?

Answer 7

NADPH

Question 8

Where does FA synthesis primarily occur?

Answer 8

The Liver

Question 9

Phase I steps

Answer 9

Cytosolic entry of ACoA

• Transport of ACoA from Mitochondria to the Cytoplasm
• ACoA ——> Citrate
• Citrate transported into the cytosol via the Citrate transporter
• Citrate ——> ACoA
• OAA ——> Pyruvate ——>OAA
  (Cytosol) (Cytosol) (Mitoch)

Question 10

Synthesis of VLDL

Answer 10

TAg packaged with Apoproteins to form VLDL

• Secreted into the blood

Question 11

What is the C-donor used in the Mitochondria?

Answer 11

ACoA

Question 12

How many reactions must take place in order to create palmitate from Malonyl CoA?

Answer 12

7

Question 13

Major Steps in the synthesis of FA?

Answer 13

3 Phases

I: Cytosolic entry of ACoA

II: Generation of Malonyl CoA

III: FA chain formation

Question 14

How many saturases ado human possess?

Answer 14

4 total

Desaturase 4, 5 , 6 & 9

Question 15

Phase II Steps

Answer 15

ACoA ——> Malonyl CoA

• Catalyzed by ACoA Carboxylase (ACC)
• Add CO2 to ACoA
• Uses ATP for energy
• Uses Biotin as a Co-factor

Question 16

What LOWERS the FA synthesis?

Answer 16

Starvation and High Fat Diets

Question 17

TAG Synthesis Summary

1. Precursors
2. Backbone
3. Net Result
4. Release

Answer 17

1. Glucose, Glycerol, and FA
2. G-3-P
3. Formation of VLDL
4. Released into the blood

Question 18

Major regulatory enzymes in all the phases of the FAS

Answer 18

I: ATP Citrate Lyase

II: ACoA Carboxylase

III: FA Synthase

Question 19

Desaturation of FA’s

1. Location
2. Reactants
3. Enzyme

Answer 19

1. SER
2. NADPH (or NADH) and O2
3. ACoA Desaturases

Question 20

Palmitate Synthesis Rxn

Answer 20

1 ACoA + 7 MCoA + 14 NADPH + 14 H+

————>

Palmitate + 14 NADP+ + 8CoA + 6 H2O

Question 21

Carbon structure of palmitate?

Answer 21

16:0

Question 22

FASynthase

Answer 22

• Multi-enzyme complex
• 2 identical DIMERS
• Arranged in Head to Tail confirmation
• Has 7 enzyme activities
• Has Acyl carrier protein (ACP)

Question 23

Where is the major source of Carbon for Fatty Acid Synthesis?

Answer 23

Dietary Carbs

Question 24

What is the C-donor used in the SER?

Answer 24

Malonyl CoA

“S&M”

Question 25

What can enter the inside of the Mitochondrial matrix

Answer 25

Both Malate and Pyruvate can both enter the Mitochondria - Malate via the Malate-alpha-ketoglutarate transporter - Pyruvate via the Pyruvate transporter

Question 26

Phase III Steps?

Answer 26

FA Chain Formation - 2C of Malonyl CoA are attached to the growing fatty acyl chain to form palmitate

Question 27

TAGs contain ____ times more energy as Carbs (Glycogen)

Answer 27

6.75

Question 28

General cycle of FAS

Answer 28

* Needs Cysteine* 1. Condensation 2. Reduction 3. Dehydration 4. Reduction - Repeat 6 more times “CRDR - CRazy DR.”

Question 29

Allosteric Regulation of ACoA Carboxylase. 1. Positive 2. Negative

Answer 29

1. Citrate | 2. Long chain FA (Palmitate)

Question 30

What is Leptin?

Answer 30

Hormone that suppresses the activity ATP Citrate Lyase - Let’s you know that you are full

Question 31

How does Malate ——> OAA?

Answer 31

It is OXIDIZED by Malate Dehydrogenase

Question 32

ATP Citrate Lyase Regulation 1. Stimulation 2. Inductors of gene expression 3. Induction counteracted by ?

Answer 32

1. Phosphorylation 2. Glucose/Insulin 3. Poly-unsaturated FA (PUFA) & Leptin

Question 33

Gene expression of the regulatory enzymes of FAS are induced by ____?

Answer 33

- Low Fat - High CARB diet - Insulin - Glucocorticoid hormones

Question 34

Where are the secondary sources for FA synthesis?

Answer 34

4 sources - Brain - Adipose tissue - Mammary glands (lactating) - Kidneys “BAMK”

Question 35

What is the rate limiting step of Fatty Acid synthesis?

Answer 35

Formation for Malonyl CoA from ACoA

Question 36

What is used as a co-factor in the conversion of ACOA to Malonyl CoA

Answer 36

Biotin