Lipid Metabolism

Question 1

The majority of carbons that contribute to FA synthesis come from where?

Answer 1

-carbohydrates that are ingested, and undergo the first few steps of glycolysis. Specifically form DHAP or G3P

Question 2

Where is FA synthesis most common in occurring?

Answer 2

brain, liver, kidneys and are stored in adipocytes

Question 3

In the cells where does FA synthesis occur?

Answer 3

cytoplasm

Question 4

What are the starting units and the addition units of FA synthesis?

Answer 4

• starts with acetyl CoA

- Malonyl CoA contributes 2 C additions to the growing FA chain

Question 5

What is the primary electron carrier that is used?

Answer 5

NADP+—–> NADPH

Question 6

What is the committed/rate limiting step in FA synthesis?

Answer 6

conversion of Acetyl CoA to Malonyl CoA via acetyl CoA carboxylase

Question 7

What are the 3 steps in FA synthesis?

Answer 7

Conversion of Acetyl CoA to Malonyl CoA

• Elongation
• Desaturation

Question 8

The elongation step of FA synthesis is what?

Answer 8

-malonyl CoA donates 2 C’s to the growing FA chain

Question 9

What is the point of a desaturation reaction with FA synthesis?

Answer 9

this process allows for the addition of double bonds to the chain

Question 10

What is the coenzyme for carboxylases?

Answer 10

-biotin

Question 11

After the TCA cycle, citrate is produced and can be used to produce what components?

Answer 11

• supply C’s for FA synthesis

- use of citrate lyase to from Acetyl CoA

Question 12

What enzyme is used to convert Acetyl CoA to Malonyl CoA?

Answer 12

acetyl CoA carboxylase (ACC)

Question 13

What factors with increase or promote the activity of ACC?

Answer 13

• citrate
• insulin
• high carb/low fat diet
• available amount of B7—> biotin (which is cofactor for carboxylases)

Question 14

What factors with inhibit the activity of ACC?

Answer 14

• [Long chain FA]
• epinephrine/glucagon (signal energy burning)
• low carb/ high fat diet
• deficiency of Vit. B7

Question 15

What ways is the ACC regulated?

Answer 15

• phosphorylation pathways
• allosteric pathways
• gene expression pathways

Question 16

Fatty acid synthase is the enzyme where FA synthesis occurs. What is the structural components that allow this?

Answer 16

• 2 monomers that form a dimer
• each monomer has 7 catalytic activities and acyl carrier proteins
• the acyl carrier protein contains a phosphopantetheine group that binds with the other monomers cysteinyl sulfhydryl group. (thioester bond)

Question 17

What are the four stages of the FA synthesis process?

Answer 17

• condensation: loss of ACP, and CO2
• reduction: NADPH—> NADP+
• dehydration: loss of water
• reduction: NADPH—> NADP+

Question 18

What three enzymes are used in the desaturation of FA in order, and what is the final product?

Answer 18

• NADH cytochrome b5 reductase
• cytochrome b5
• stearoyl CoA desaturase: produces oleoyl CoA and water

Question 19

What are the two main components required for TAG synthesis?

Answer 19

TAGs can form from glycerol or glucose. The main intermediate is G-3-P

Question 20

What are the steps to forming TAGs?

Answer 20

G-3-P converts to phosphatidic acid; converts to diacylglycerol; converts to TAG and combine with apoproteins to move to the liver as very low density lipoproteins

Question 21

What is needed to form eicosanoids?

Answer 21

phospholipids and diacylglycerols

Question 22

What are the types of eicosanoids that exist?

Answer 22

• leukotriene (B4)
• prostacyclin (PGI2): vasodilator
• thromboxane A2: vasoconstrictor
• prostaglandin (E2)

Question 23

Lipoxygenases form what type of eicosanoids?

Answer 23

-leukotrienes

Question 24

Prostaglandin synthase forms what type of eicosanoids?

Answer 24

• prostaglandin
• prostacyclin
• thromboxane

Question 25

What are the products of phosphatidic acid in the mechanism 1?

Answer 25

• phosphatidylcholine

- phosphatidylethanolamine

Question 26

What products form from mechanism 2 from phosphatidic aicd?

Answer 26

• phosphatidylinositol

- cardiolipin: major component of mito. matrix

Question 27

What is the main difference between mechanism 1 and 2 in the phospholipid synthesis?

Answer 27

the main difference is where the CDP head group attaches to the diacylglycerol.

• mech 1: adds CDP-head group in one step
• mech 2: adds CDP and then adds the head group.

Question 28

What component is the primary “hub” for forming phosphatidylserine/choline?

Answer 28

• PE is swapped to PS

- PE if methylated forms PC

Question 29

Cholesterol is derived from what?

Answer 29

Acetyl CoA and Acetoacetyl CoA

Question 30

What is the rate limiting/control step of cholesterol production?

Answer 30

• HMG CoA Reductase
• -converts acetyl CoA to mevalonate.
• -produces 2 NADP+ and CoA

Question 31

Where do statins work primarily to reduce the level of cholesterol?

Answer 31

-at HMG CoA reductase, the rate limiting step

Question 32

What happens during fasting after mevalonate is formed? There is a second compound produced, what is it and what will it do?

Answer 32

• acetyl CoA and acetoacetate

- -instarvation acetyl CoA forms ketone bodies

Question 33

Stage 2 of cholesterol synthesis is how many steps, and how many C’s from start to finish?

Answer 33

• occurs in three reactions and start with 5–>10–>15–>20 C’s
• squalene is able to begin the ring cyclization of cholesterol.

Question 34

What is the name of the enzyme that helps stabilize the structure for ring formation?

Answer 34

-oxidosqualene cyclase, maintains the ring structure of the intermediates until stabile cholesterol is formed

Question 35

The accumulation of cholesterol is what?

Answer 35

LDL that allows release into blood stream and delivers cholesterol to the liver and peripheral tissue

Question 36

HDL is able to transfer APoE and APoCII to what molecules?

Answer 36

• chylomicrons
• VLDL
• IDL
• LDL

Question 37

If a person has a cholesterol ester transfer protein mutation or deficiency what is the ultimate problem?

Answer 37

-TAG and phospholipids are not able to transfer from LDL, VLDL, IDL to HDL.