Metabolism: Lipid Metabolism

Question 1

Recall the 4 uses of acetyl-CoA.

Answer 1

1. TCA
2. ketone bodies
3. cholesterol synthesis
4. fatty acid synthesis

Question 2

What are the 3 enzymes important for fatty acid synthesis?

Answer 2

1. acetyl-CoA carboxylase
2. carnitine palmitoyltransferase1
3. FAS complex

Question 3

What is the rate-limiting enzyme for FA synthesis?

Answer 3

acetyl-CoA carboxylase

Question 4

Describe the fate of lipid metabolism during fed state.

Answer 4

• increased BG => increased insulin => activation of ACC, inhibition of CPT1 => increased TAG synthesis
• increased acetyl-CoA => increased cholesterol synthesis

Question 5

Describe the fate of lipid metabolism during starvation.

Answer 5

• decreased BG => increased glucagon => activation of CPT1, inhibition of ACC
• TAG is degraded into glycerol and fatty-acyl-CoAs
• CPT1 takes fatty acyl-CoAs => acetyl-coA
• aCoA used to make ketone bodies

Question 6

What is the function of acetyl-CoA carboxylase?

Answer 6

2 acetyl-CoA + CO2 => 7 malonyl-CoA

Question 7

What is the function of carnitine palmitoyltransferase?

Answer 7

fatty-acyl-CoA => acetyl-CoA

Question 8

Describe fatty acid transport and metabolism during fed state.

Answer 8

1. dietary TAG transported to the liver via chylomicrons
2. glucose used to generate more TAG
3. transported in lipoproteins to store in adipose or muscles

Question 9

Describe fatty acid transport and metabolism during starvation.

Answer 9

1. stored TAG in adipose and muscles broken down to make glycerol and fatty acyl-CoA
2. exported to the liver attached to albumin
3. generate acetyl-CoA => ketone bodies
4. gluconeogenesis

Question 10

What is an essential FA?

Answer 10

linoleic acid

found in omega-3

Question 11

What is the function of FAS?

Answer 11

1 acetyl-CoA + 7 malonyl-CoA + NADPH => palmitate

Question 12

What is the function of citrate in fatty acid metabolism?

Answer 12

• used to transport acetyl-CoA out of the mitochondria (leaves mitochondria, convered to OAA and aCoA)
• allosteric activator of ACC

Question 13

What are the 5 things required for fatty acid synthesis?

Answer 13

• acetyl groups via citrate
• ACC
• biotin - activated CO2
• NADPH
• FAS

Question 14

What is the cofactor for ACC?

Answer 14

biotin

Question 15

Describe the allosteric control of ACC.

Answer 15

activator - citrate

inhibitor - palmitoyl-CoA, AMPK

Question 16

Describe the function of malonyl-coA.

Answer 16

• key regulator of fatty acid oxidation and ketone body formation
• physiological (coarse) control of ACC
• made by ACC

Question 17

Why is AMPK an inhibitor of ACC?

Answer 17

because indicates we don’t have enough energy. We don’t need to store TAG we need to break it down and utilize it for energy

Question 18

What are long-term activators of ACC and FASC synthesis?

Answer 18

• high carb diet
• insulin
• thyroid hormone (only ACC)
• fat free diet (will want to store as much as it can?)

Question 19

What are long-term inhibitors of ACC and FASC synthesis?

Answer 19

• high fat diet (causes low insulin and high glucagon)
• fasting
• glucagon

Question 20

What are short-term activators of FASC?

Answer 20

F16BP (allosteric) => higher glucose => higher pyruvate => higher acetyl-CoA => activates FASC

Question 21

What is the long-term goal of fatty acid synthesis?

Answer 21

• via esterification and elongation you can generate TAG, cholesterol, or phospholipids

Question 22

How can you endogenously generate TAG?

Answer 22

• depends on substrate availability

- activated by PRARs (peroxisome proliferator-activated receptors)

Question 23

How is TAG transported?

Answer 23

VLDL apolipoproteins