Biosynthesis and Storage of FAs and TAG (Exam 2)

Question 1

Where does de novo synthesis of FAs occur?

Answer 1

LIVER

Some in the mammary gland during lactation

Question 2

What is the source of carbons for FA synthesis? **

Answer 2

Acetyl-CoA fragments***

Coming from excess dietary carbohydrates and proteins

Question 3

Where is the source of carbons for FA synthesis?

Answer 3

Acetyl-CoA fragments will be locked away in the mitochondria

Question 4

Where does FA synthesis occur?

Answer 4

CYTOPLASM

Question 5

(TRUE/FALSE)

The acetyl-CoA for FA synthesis must be taken from the mitochondria and transported into the cytoplasm.

Answer 5

TRUE**

Remember, it is INSIDE the MITO where we break down nutrients and that is where we make ATP.

Question 6

How are the acetyl-CoA transported out of the mitochondria and into the cytoplasm?

Answer 6

1. As the 1st step in the Krebs Cycle, Acetyl-CoA will complex with OAA via CITRATE SYNTHASE
2. Citrate will then cross the mito membrane and enter the cytosol
3. Citrate will be split via ATP CITRATE LYASE to form OAA and Acetyl-CoA

Question 7

What is the enzyme that splits CITRATE in the cytoplasm?

Answer 7

CITRATE LYASE

Question 8

What is the enzyme that complexes/combines OAA and Acetyl-CoA in the mitochondria?

Answer 8

CITRATE SYNTHASE

Question 9

What is the first step in FA synthesis?

Answer 9

Acetyl-CoA is converted to Malonyl-CoA via ACETYL-COA CARBOXYLASE (ACC)

Question 10

ACC (function)

Answer 10

Acetyl-CoA Carboxylase, a rate-limiting enzyme**

Catalyzes the first reaction in FA synthesis of Acetyl-CoA —-> Malonyl-CoA

Question 11

How is ACC regulated?

Answer 11

Acetyl-CoA Carboxylase

1) Allosterically: ++ Citrate; – Palmitoyl-CoA (the final product of FA synthesis)

2) Covalent Modulation

Question 12

What is palmitoyl-CoA?

Answer 12

It is the final step in FA synthesis; which negatively effects ACC allosterically

Question 13

Explain covalent modulation of ACC.

Answer 13

1) ACTIVE = DEPHOS (High insulin/fed-state levels will activate PROTEIN PHOSPHATASE to dephos ACC, thereby activating it).

2) INACTIVE = PHOSPHORYLATED (High Glucagon, Epi/fasting-state, AMPK Kinase levels will activate AMPK to PHOS ACC, thereby inactivating it).

Question 14

What is the main fragment that is used by FA Synthase Complex for FA synthesis?

Answer 14

Malonyl-CoA, will be added on in several steps, so each time it is elongated and reduced by NADPH.

The reducing will result in a 16 carbon saturated FA called PALMITATE

Question 15

FA Synthase Complex

Answer 15

Has 2 domains:
1) Cysteine residue
2) Acyl-carrier protein

which will allow it elongated these malonyl-CoA fragments in FA synthesis

Question 16

What is the reducing agent in FA synthesis?

Answer 16

NADPH

Question 17

AMPK

Answer 17

AMP-activated protein kinase

Acts to phosphorylate ACC during fasting state, thereby inactivating it. It is allosterically regulated by ++ AMP levels.

Question 18

What increases protein phosphatase enzyme in FA synthesis? What is the result?

Answer 18

Insulin will activate Protein Phosphatase enzyme which will DEPHOSPHORYLATE ACC, thereby activating it. So Acetyl-CoA will be converted to Malonyl-CoA.

Question 19

Explain the long-term regulation of ACC.

Answer 19

Via gene expression level

1) Increased expression/activity with high carbohydrate, or low-fat diet

2) Decreased expression/activity of ACC with low-calorie, high-fat, or low carb diets.

Question 20

(TRUE/FALSE)

The body can create saturated and unsaturated fats

Answer 20

TRUE

Through elongation and desaturation of palmitate, both occurring in the smooth endoplasmic reticulum

Question 21

Explain the synthesis of TAG.

Answer 21

The FAs that are produced through FA Synthase Complex will be used to form TAG molecules within the LIVER.

The FAs must first be activated by FATTY ACETYL-COA SYNTHETASE first. This adds the CoA to each FA, allowing each FA w/ its CoA to attach to the glycerol-3-P molecule.

Question 22

What happens once TAG is synthesized in the liver?

Answer 22

It will be exported as part of VLDL and will go to peripheral tissues to serve as an energy source via LPL (remember!). (The VLDL will then transition to IDL, then LDL).