MMT: fatty acid biosynthesis

Question 1

What is the main product of fatty acid synthase?

Answer 1

Palmitic acid

Question 2

What are the transporters of fatty acids in the fed state?

Answer 2

Chylomicrons and VLDL

Question 3

What are the transporters of fatty acids in the fasting state?

Answer 3

Albumin

Question 4

In the fed state, fatty acids are released by?

Answer 4

LPL in the capillaries

Question 5

In the fasting state, fatty acids are released by?

Answer 5

Hormone-sensitive lipase in adipocytes

Question 6

What are the 4 major stages of palmitate formation?

Answer 6

1. Pyruvate formation 2. Citrate formation 3. Malonyl CoA formation 4. Palmitate

Question 7

What is the rate limiting enzyme of fatty acid synthesis?

Answer 7

Acetyl CoA carboxylase

Question 8

In the fed state, what drives the formation of citrate?

Answer 8

Acetyl CoA buildup

Question 9

How does the high insulin/glucagon ratio in the fed state drive formation of citrate?

Answer 9

It reduces the need for gluconeogenesis and upregulates glycolysis, allowing oxaloacetate that is formed to be used to make citrate

Question 10

How does a high ATP/ADP ratio in the fed state impact the formation of citrate?

Answer 10

It reduces the need for acetyl CoA to be used in the citric acid cycle, making it available to make citrate

Question 11

What enzyme is upregulated in the fasting state to promote formation of oxaloacetate?

Answer 11

Pyruvate carboxylase

Question 12

What vitamin is needed to produce malonyl CoA from acetyl CoA?

Answer 12

Biotin (acetyl CoA carboxylase)

Question 13

Malonyl CoA inhibits…? What is the significance of this?

Answer 13

CPTI; upregulates fatty acid synthesis instead of oxidation

Question 14

What is the ‘short arm’ of fatty acid synthase?

Answer 14

Cysteine; associated with acetyl group

Question 15

What is the ‘long arm’ of fatty acid synthase?

Answer 15

ACP; associated with malonyl group

Question 16

What is the structure of fatty acid synthase?

Answer 16

A dimer that makes 2 palmitic acids at a time

Question 17

What is the 4-reaction cycle of fatty acid synthesis?

Answer 17

1. Condensation 2. Reduction 3. Dehydration 4. Reduction

Question 18

What is used as a reducing agent in fatty acid synthesis?

Answer 18

NADPH

Question 19

Where does fatty acid synthesis occur?

Answer 19

The cytoplasm

Question 20

What happens once palmitate is formed?

Answer 20

It is released from fatty acid synthase and converted to palmitoyl CoA

Question 21

What enzyme forms palmitoyl CoA?

Answer 21

Fatty acyl CoA synthase

Question 22

What is the major control point of fatty acid synthesis?

Answer 22

Acetyl CoA carboxylase

Question 23

What are the main regulatory methods of acetyl CoA carboxylase?

Answer 23

Phosphorylation and allosteric modulators

Question 24

More citrate will __ fatty acid synthesis?

Answer 24

Promote

Question 25

More palmitoyl CoA will __ fatty acid synthesis?

Answer 25

Reduce

Question 26

Describe the regulation of ACC in the fed state.

Answer 26

Insulin promotes a phosphatase that promotes formation of malonyl CoA and thus inhibition of CPTI. This leads to synthesis of fatty acids.

Question 27

Describe the regulation of ACC in the fasting state.

Answer 27

High AMP causes AMPK to phosphorylate ACC, causing less malonyl CoA. This will promote fatty acid oxidation as opposed to synthesis.

Question 28

What enzymes upregulate fatty acid synthesis due to insulin?

Answer 28

Malic enzyme and citrate lyase

Question 29

Elongation of fatty acids occurs in the…

Answer 29

ER

Question 30

Where does VLC FA oxidation take place?

Answer 30

Peroxisomes

Question 31

What are the steps for elongation of fatty acids?

Answer 31

Same as synthesis! 1. Condensation 2. Reduction 3. Dehydration 4. Reduction

Question 32

In unsaturated fatty acids, where can we introduce double bonds?

Answer 32

Carbon 4, 5, 6, and 9, but not beyond 9!!

Question 33

What is fatty acyl CoA desaturase?

Answer 33

A membrane-bound oxygenase that desaturates fatty acids in the ER

Question 34

What does desaturation require to occur?

Answer 34

Iron

Question 35

What are the main functional roles of fatty acids?

Answer 35

1. Serve as fuel 2. Make up TGs and phosphoacylglycerols 3. Serve as hormones and intracellular messengers

Question 36

Why does the brain not use free fatty acids for fuel?

Answer 36

1. ATP generation from beta oxidation demands more oxygen than from glucose, which increases risk of neural hypoxia 2. Superoxide is generated in beta oxidation which can cause oxidative stress 3. Rate of ATP generation is slower than that of glucose

Question 37

What is the starting molecule for phosphoacylglycerol?

Answer 37

G3P

Question 38

Other than cell membranes, where can phosphoacylglycerols be found?

Answer 38

Outside of lipoproteins

Question 39

What are eicosanoids?

Answer 39

Molecules formed from arachidonic acid that act as local hormones; they can cause inflammation, clotting, smooth muscle contraction, etc

Question 40

Where is arachidonic acid in the cell membrane?

Answer 40

In the fatty acid tails of phospholipids

Question 41

What are the pathways of eicosanoid synthesis?

Answer 41

COX and LOX

Question 42

Aspirin and ibuprofen block…

Answer 42

COX