Lecture 13

Question 1

What are the domains in fatty acid synthase?

Answer 1

Malonyl/acetyl-CoA/ACP transacylase (MAT)

KS (ketone synthase), KR (ketoreductase), DH (dehydratase), ER (enoyl-reductase), and TE (thioesterase)

Question 2

What is step 1 in the fatty acid synthase process of fatty acid biosynthesis (assume malonyl-CoA was already made)?

Answer 2

MAT adds starting acetyl-CoA to malonyl-CoA, the latter of which is attached to fatty acid synthase by its thiol group

Question 3

With which step is the first step of fatty acid synthase parallel to in beta-oxidation?

Answer 3

Products of thiolytic cleavage

Question 4

What is step 2 in the fatty acid synthase process?

Answer 4

Ketone synthase (KS) carries out the condensation reaction. Releases CO2 so that acetyl-CoA can attach

Question 5

What is step 3 in the fatty acid synthase process?

Answer 5

Ketone reductase (KR) reduces the beta-carbon ketone to an alcohol, using NADPH as an electron donor

Question 6

What is step 4 in the fatty acid synthase process?

Answer 6

Dehydratase converts beta-carbon hydroxyl to carbon-carbon double bond

Question 7

What is step 5 in fatty acid synthase?

Answer 7

Enoyl-reductase (ER) reduces the carbon-carbon double bond to hydrocarbons. NADPH used as electron donor.

Question 8

What is step 6 in fatty acid synthase?

Answer 8

Repeat steps 2-5 as needed

Question 9

What is step 7 in fatty acid synthase?

Answer 9

Thioesterase (TE) releases the final product, a fatty acid

Question 10

How many ATP and NADPH does one round of fatty acid biosynthesis consume?

Answer 10

1 ATP and 2 NADPH

Question 11

Differences between beta-oxidation and fatty acid biosynthesis?

Answer 11

beta-oxidation: CoA is the acyl carrier, FAD and NAD+ are the electron acceptors, L-beta-hydroxyacyl group in dehydration step, C2 unit product is acetyl-CoA

FA biosynthesis: ACP is the acyl carrier, NADPH is the electron donor, D-beta-hydroxyl group in hydration step, C2 unit donor is malonyl-CoA

Question 12

How does eating Omega-3/6 fatty acids affect inflammatory responses?

Answer 12

They reduce inflammation responses. Paradoxically, they also increase inflammatory response?

Question 13

What do NSAIDs do?

Answer 13

They inhibit the conversion of arachidonic acid (Omega-6 FA) and eicosapentaenoic acid (Omega-3 FA) to downstream products that increase inflammation response.

Question 14

What does phospholipase do in inflammatory response?

Answer 14

It releases a free FA to make prostaglandins

Question 15

What are 2 essential FAs? Do we synthesize them?

Answer 15

Linoleate and alpha-linolenate. We do not synthesize them, rather we eat them from fish, who eat the plants that have the FAs.

Question 16

What are the 2 precursors for making glycerophospholipids?

Answer 16

Fatty acyl-CoA and L-glycerol 3-P

Question 17

How to make L-glycerol 3-P?

Answer 17

Glyceroneogenesis, where glycerol kinase converts glycerol to L-glycerol 3-P (Requires ATP input. Release ADP). Can also get it from glycolysis and gluconeogenesis.

Question 18

Describe phospholipid synthesis. Alternative path?

Answer 18

Acyl-CoA synthetase converts fatty acid to fatty acyl-CoA, which reacts with L-glycerol 3-P to form an acid. A head group is attached to make a glycerophospholipid. An alternative path is to make DAG and then TAG from the acid.

Question 19

Do we have a mechanism to degrade cholesterol?

Answer 19

No. It must either be used or excreted through the liver.

Question 20

When do we make cholesterol?

Answer 20

After we eat. Maybe to make bile salts?

Question 21

Describe big-picture cholesterol synthesis

Answer 21

1. Acetate
2. Mevalonate (commited to making isoprene)
3. Isoprene
4. Squalene
5. Cholesterol

Question 22

Describe mevalonate synthesis

Answer 22

1. 2 Acetyl-CoA react via thiolase to make acetoacetyl-CoA
2. Another acetyl-CoA is added to make HMG-CoA via HMG-CoA synthase
3. HMG-CoA reductase uses 2 NADPH to reduce HMG-CoA to mevalonate

Question 23

Where does mevalonate synthesis occur?

Answer 23

Cytosol, so it doesn’t compete with ketogenesis in the mitochondria

Question 24

Which hormones regulate HMG-CoA reductase?

Answer 24

Glucagon inhibits it bc don’t want to make fatty acids when hungry
Insulin activates it bc want to make fatty acids (for bile salts?)

Question 25

What do statins do?

Answer 25

They prevent cholesterol synthesis by COMPETITIVELY inhibiting HMG-CoA reductase. It’s a billion dollar industry.

Question 26

How does glucagon regulate HMG-CoA reductase?

Answer 26

It phosphorylates the enzyme, which deactivates it

Question 27

How does insulin regulate HMG-CoA reductase?

Answer 27

It dephosphorylates the enzyme, which activates it

Question 28

How do ATP and AMP concentrations regulate cholesterol synthesis?

Answer 28

High ATP/low AMP -> increased cholesterol synthesis

Low ATP/high AMP -> decreased cholesterol synthesis

Question 29

How does diabetes mellitus affect people?

Answer 29

Cannot use glucose for glycolysis AND CANNOT make fatty acids from carbs or amino acids

Question 30

Describe the big-picture version of glyceroneogenesis

Answer 30

It’s the abbreviated version of gluconeogenesis, from pyruvate to DHAP - > glyceraldehyde 3-P -> TAGs