Fatty Acid, Triglycerides, & Cholesterol Synthesis

Question 1

Where does FA synthesis take place?

Answer 1

Liver & lactating mammary glands

Question 2

What reactants are required for FA/TG synthesis?

Answer 2

Acetyl CoA, NADPH, ATP

Question 3

Acetyl CoA is required for FA/TG synthesis? Where is this Acetyl CoA obtained?

Answer 3

Citrate produced in TCA begins to accumulate in the mitochondria and is transported to the cytosol. Here, the citrate lyase produces OAA and Acetyl CoA from citrate. The Acetyl CoA can be used for FA/TG synthesis

Question 4

The citrate lyase produced acetyl CoA and OAA. What is the fate of OAA?

Answer 4

OAA is converted to Malate by the cytosolic malate dehydrogenase. Malate is then converted to pyruvate by the malic enzyme to re-enter TCA. This also produced NADPH, which can be used in FA/TG synthesis.

Question 5

Describe the process of FA synthesis.

Answer 5

Acetyl CoA is converted to Malonyl CoA by the Acetyl CoA Carboxylase. This step requires CO2, ATP, and Biotin.

The FA synthase forms a 4-chain FA through carbonyl attack of malonyl CoA on acetyl CoA.

2 carbons are added to the growing FA with each step to ultimately produce Palmitate (16C).

Question 6

Palmitate is the product of FA synthesis. How can the FA be further elongated?

Answer 6

Only fatty-acyl CoA molecules can be elongated. The Fatty Acyl-CoA Synthetase activated a free-floating FA. The FA elongase added malonyl CoA to the existing FA in a process similar to FA synthesis. Elongation happens in the SER.

Question 7

How are FAs desaturated?

Answer 7

FAs are desaturated by the Fatty Acyl CoA Desaturase. This process only takes place in the ER.

Question 8

True/False. Humans cannot desaturate bones between omega 1-6.

Answer 8

True. Omega 6 or less cannot be unsaturated. This is where Omega 3 and 6 are essential FAs.

Question 9

What is the key enzyme of FA synthesis? How is this enzyme regulated?

Answer 9

Acetyl CoA Carboxylase - stimulated by Citrate, inhibited by Palmitoyl CoA, stimulated by dephosphorylation by insulin

Question 10

What enzyme phosphorylates and inactivates Acetyl CoA Carboxylase?

Answer 10

AMP-Activated Protein Kinase

Question 11

What enzymes involved in FA synthesis are induced by insulin?

Answer 11

Citrate lyase, Acetyl CoA Carboxylase, G-6-P Dehydrogenase, Malic Enzyme, FA Synthase

Question 12

What is the role of G-6-P Dehydrogenase in FA synthesis?

Answer 12

G6PDH plays a role in the oxidative cycle of the PPP. This produces NADPH used in FA synthesis.

Question 13

What enzyme adds acyl-CoA chains to a growing triglyceride?

Answer 13

Acyltransferase

Question 14

What is the starting backbone of a triglyceride?

Answer 14

Glycerol-3-Phosphate

Question 15

How does TG synthesis vary in the small intestine, liver, and adipocytes?

Answer 15

Small Intestine - Chylomicrons

Liver - Very Low-Density Lipoprotein

Adipocytes - Storage

Question 16

What is the backbone of glycerophospholipids? How are these molecules synthesized?

Answer 16

Glycerol-3-Phosphate is the backbone for glycerophospholipids. The molecules are synthesized by either activating the phosphatidic acid to CDP-diacylglycerol or activating the X to CDP-X.

Question 17

How do sphingolipids differ from glycerophospholipids? How are sphingolipids synthesized?

Answer 17

Sphingolipids have a sphingosine backbone, whereas glycerophospholipids have a glycerol backbone.

Palmitoyl-CoA and Serine are combined to form ceramide. A choline group from phosphatidylcholine is added to ceramide to form a sphingolipid.

Question 18

What molecule is a precursor for cholesterol synthesis?

Answer 18

Mevalonate

Question 19

How is Cholesterol synthesized?

Answer 19

Cholesterol synthesis occurs in 3 phases and requires acetyl-CoA and NADPH.

Acetyl CoA and Acetoacetyl CoA are combined by the HMG CoA Synthase to form HMG-CoA. HMG-CoA is reduced by the HMG-CoA Reductase to form Mevalonate. Mevalonate is a cholesterol precursor that enters phases 2 and 3 to form cholesterol.

Question 20

What is the rate-limiting step of cholesterol synthesis?

Answer 20

HMG-CoA Reductase (HMG-CoA –> Mevalonate)

Question 21

What are the four mechanisms in which the HMG-CoA Reductase is regulated?

Answer 21

Stimulated by insulin or thyroid hormone, proteolytic degradation, inactivation by phosphorylation, inhibition by Cholesterol

Question 22

How do statins reduce cholesterol levels?

Answer 22

Inhibit cholesterol synthesis by inhibiting the HMG CoA Reductase

Question 23

Ketone synthesis is similar to cholesterol synthesis. How do these processes differ?

Answer 23

Ketone synthesis takes place in the mitochondria and is induced by glucagon. Cholesterol synthesis takes place in the cytoplasm and is induced by insulin.

Question 24

What enzyme esterifies cholesterol?

Answer 24

Acyl-CoA Cholesterol Acyl Transferase (ACTH)