Lecture 32: Lipid Anabolism

Question 1

Fatty Acid Synthesis Overview

Where does FA synthesis occur?

Answer 1

in the cytosol

Question 2

Fatty Acid Synthesis Overview

What provides the first 2 carbons for the synthesis?

Answer 2

Acetyl-CoA

Question 3

Fatty Acid Synthesis Overview

What provides the later carbons?

Answer 3

malonyl-CoA donating 2C units

Question 4

Fatty Acid Synthesis Overview

What are immediates attached to on an acyl carrier protein (ACL)?

Answer 4

the -SH groups

Question 5

Fatty Acid Synthesis Overview

What is the reductant in FA synthesis?

Answer 5

NADPH

Question 6

Fatty Acid Synthesis Overview

When does elongation by the fatty acid synthase complex stop?

Answer 6

When it forms palmitate (C16)

further elongation and unsaturation is down by other enzyme systems

Question 7

Fatty Acid Synthesis Overview

What is the multi-enam system for fatty acid synthesis called?

Enams can be in one polypeptide chain for higher organisms

Answer 7

Fatty Acid Synthase

Question 8

Formation of Malonyl Coenzyme A

What is the commited step in FA synthesis?

Answer 8

Synthesis of malonyl-CoA

rate limiting step

Question 9

Formation of Malonyl Coenzyme A

What is the equation involing malonyl-CoA synthesis?

Answer 9

Acetyl-CoA + HCO3 + ATP
-(acetyl-CoA carboxylase)->
Malonyl-CoA + ADP + Pi + H

Question 10

Formation of Malonyl Coenzyme A

What controls the rate of FA biosynthesis?

Answer 10

acetyl-CoA carboxylase

Question 11

Formation of Malonyl Coenzyme A

How is acetyl-CoA carbocylase activated/deactivated?

Answer 11

Activated: dephosphorylation
Deactivated: phosphorylation

Question 12

Formation of Malonyl Coenzyme A

How are the intermediated linked to the ACP for transport?

Answer 12

covalently

Question 13

Formation of Malonyl Coenzyme A

What is the enam called that links the acetyl/malonyl to ACP?

Answer 13

“Name” transacylase
ex: acetyl transacylase
ex: malonyl transacylase

Question 14

Fatty Acid Synthesis

What is the overall goal of FA synthesis?

Answer 14

to attach 2 carbon acetate unit from malonyl-CoA to a growing chain then reduce it

Question 15

Fatty Acid Synthesis

What are the 4 enzyme catalized steps of elongation cycles?

Answer 15

1. Condensation (produce CO2 and ACP)
2. Reduction (Uses NADPH, Produces NADP)
3. Dehydration (Produces H2O)
4. Reduction (Uses NADPH, Produces NADP)

Question 16

Enzymes in Elongation Cycle

What is the enzyme in step 1?

Condensation

Answer 16

b-ketoacyl-ACP synthase (KS)

produces: acetoacetyl ACP

Question 17

Enzymes in Elongation Cycle

What is the enzyme in step 2?

Reduction

Answer 17

b-ketoacyl-ACP reductase (KR)

produces: D-3-hydroxbutyryl ACP

Question 18

Enzymes in Elongation Cycle

What is the enzyme in step 3?

Dehydration

Answer 18

b-hydroxyacyl-ACP dehydratase (DH)

produces: Crotonyl ACP

Question 19

Enzymes in Elongation Cycle

What is the enzyme in step 4?

Reduction

Answer 19

enoyl-ACP reductase (ER)

Produces Butyryl ACP

Question 20

Elongation Cycle

What does this elongation cycle look similar to?

Answer 20

The last 3 reactions are similar to the reverse of the fatty acid degradation, with some exceptions
* NADPH instead of NADH and FADH2
* D-enantiomer instead of L-enantiomer of hydroxybutarate

Question 21

Elongation Cycle

What does the second cycle begin with?

Answer 21

the condensation of butyryl ACP and malonyl ACP (repeats cycle until reaching 16C, 7 cycles)

Question 22

Elongation Cycle

What cleaves the palmityl-CoA from the ACP since it has reached 16C?

Answer 22

Thioesterase

Question 23

Elongation Cycle

Where is further elongation and unsaturation happening?

Answer 23

in the endoplasmic reticulum by other enzymes

Question 24

Elongation Cycle

What is the net equation of the synthesis of palmaitate from malonyl-CoA?

Answer 24

Acetyl CoA + 7 malonyl CoA + 14 NADPH + 20 H
–>
palmitate + 7 CO2 + 14 NADP + 8 CoA + 6 H2O

Question 25

Elongation Cycle

What is the net equation of the synthesis of malonyl-CoA from acetyle-CoA?

Answer 25

7 Acetyl CoA + 7 CO2 + 7 ATP
–>
7 malonyl CoA + 7 ADP + 7 Pi + 14 H

Question 26

Elongation Cycle

What is the net equation of the overall synthesis of palmitate from acetyl CoA in cytosol?

Answer 26

8 Acetyl CoA + 7 ATP + 14 NADPH + 6 H
–>
palmitate + 14 NADP + 8 CoA + 6 H2O + 7 ADP + 7 Pi

Question 27

Citrate Shuttle

How are acetyl-CoA units moved out of the mitochondrial matrix (where they are formed) to the cytosol (to form fatty acids)?

Answer 27

As citrate: Acetyl-CoA reacts with oxaloacetate to form citrate

Citrate is cleaved by ATP-citrate lyase (consumes 1 ATP) to form back to acetyl-CoA and oxaloacetate

Question 28

Biosynthesis of triaclglycerols and phospholipids

What are the two fates of newly synthesized FA in cells?

Answer 28

1. Incorporated into tryacylglycerols for long term energy storage
2. be incorporated into membrane phospholipids

Question 29

Biosynthesis of triaclglycerols and phospholipids

What is the precursor for the backbone of fat and phospholipids?

Answer 29

glycerol-3-phosphate, which is derived from DHAP (intermediate of glycolysis)

Question 30

Biosynthesis of triaclglycerols and phospholipids

How is phosphatidic acid formed?

Answer 30

Acyl transferases attach two fatty acids to glycerol-3-phosphate

Question 31

Biosynthesis of triaclglycerols and phospholipids

What is phosphatidic acid the precursor for?

Answer 31

triacylglycerols and phospholipids

Question 32

Biosynthesis of triaclglycerols and phospholipids

What is done to phosphatidic acid to make triacylglycerols?

Answer 32

It is dephosphorylated (by phosphotase) then acylated (by acyl transferase) to add third acylglycerol group

Question 33

Biosynthesis of triaclglycerols and phospholipids

What is done to phosphatidic acid to make phospholipids?

Answer 33

Head group is attached onto phosphate