Lecture 32: Lipid Anabolism Flashcards

1
Q

Fatty Acid Synthesis Overview

Where does FA synthesis occur?

A

in the cytosol

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2
Q

Fatty Acid Synthesis Overview

What provides the first 2 carbons for the synthesis?

A

Acetyl-CoA

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3
Q

Fatty Acid Synthesis Overview

What provides the later carbons?

A

malonyl-CoA donating 2C units

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4
Q

Fatty Acid Synthesis Overview

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

A

the -SH groups

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5
Q

Fatty Acid Synthesis Overview

What is the reductant in FA synthesis?

A

NADPH

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6
Q

Fatty Acid Synthesis Overview

When does elongation by the fatty acid synthase complex stop?

A

When it forms palmitate (C16)

further elongation and unsaturation is down by other enzyme systems

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7
Q

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

A

Fatty Acid Synthase

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8
Q

Formation of Malonyl Coenzyme A

What is the commited step in FA synthesis?

A

Synthesis of malonyl-CoA

rate limiting step

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9
Q

Formation of Malonyl Coenzyme A

What is the equation involing malonyl-CoA synthesis?

A

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

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10
Q

Formation of Malonyl Coenzyme A

What controls the rate of FA biosynthesis?

A

acetyl-CoA carboxylase

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11
Q

Formation of Malonyl Coenzyme A

How is acetyl-CoA carbocylase activated/deactivated?

A

Activated: dephosphorylation
Deactivated: phosphorylation

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12
Q

Formation of Malonyl Coenzyme A

How are the intermediated linked to the ACP for transport?

A

covalently

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13
Q

Formation of Malonyl Coenzyme A

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

A

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

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14
Q

Fatty Acid Synthesis

What is the overall goal of FA synthesis?

A

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

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15
Q

Fatty Acid Synthesis

What are the 4 enzyme catalized steps of elongation cycles?

A
  1. Condensation (produce CO2 and ACP)
  2. Reduction (Uses NADPH, Produces NADP)
  3. Dehydration (Produces H2O)
  4. Reduction (Uses NADPH, Produces NADP)
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16
Q

Enzymes in Elongation Cycle

What is the enzyme in step 1?

Condensation

A

b-ketoacyl-ACP synthase (KS)

produces: acetoacetyl ACP

17
Q

Enzymes in Elongation Cycle

What is the enzyme in step 2?

Reduction

A

b-ketoacyl-ACP reductase (KR)

produces: D-3-hydroxbutyryl ACP

18
Q

Enzymes in Elongation Cycle

What is the enzyme in step 3?

Dehydration

A

b-hydroxyacyl-ACP dehydratase (DH)

produces: Crotonyl ACP

19
Q

Enzymes in Elongation Cycle

What is the enzyme in step 4?

Reduction

A

enoyl-ACP reductase (ER)

Produces Butyryl ACP

20
Q

Elongation Cycle

What does this elongation cycle look similar to?

A

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

21
Q

Elongation Cycle

What does the second cycle begin with?

A

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

22
Q

Elongation Cycle

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

A

Thioesterase

23
Q

Elongation Cycle

Where is further elongation and unsaturation happening?

A

in the endoplasmic reticulum by other enzymes

24
Q

Elongation Cycle

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

A

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

25
Q

Elongation Cycle

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

A

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

26
Q

Elongation Cycle

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

A

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

27
Q

Citrate Shuttle

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

A

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

28
Q

Biosynthesis of triaclglycerols and phospholipids

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

A
  1. Incorporated into tryacylglycerols for long term energy storage
  2. be incorporated into membrane phospholipids
29
Q

Biosynthesis of triaclglycerols and phospholipids

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

A

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

30
Q

Biosynthesis of triaclglycerols and phospholipids

How is phosphatidic acid formed?

A

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

31
Q

Biosynthesis of triaclglycerols and phospholipids

What is phosphatidic acid the precursor for?

A

triacylglycerols and phospholipids

32
Q

Biosynthesis of triaclglycerols and phospholipids

What is done to phosphatidic acid to make triacylglycerols?

A

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

33
Q

Biosynthesis of triaclglycerols and phospholipids

What is done to phosphatidic acid to make phospholipids?

A

Head group is attached onto phosphate