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2) Biochemistry II > Lipid Biosynthesis > Flashcards

Lipid Biosynthesis Flashcards

(53 cards)

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1
Q

Name the biological functions of lipids.

A
  • Energy storage (TG)
  • Constituents for membranes
  • Anchors for membrane proteins (prenyl group, IP2/PIP3)
  • Cofactors for enzymes (vitamin K)
  • Signaling molecules (eicosanoids, IP3)
  • Pigments (retinal); important for vision
  • Detergents (bile salts); help the absorption of lipids and fats from the diet
  • Transporters
  • Antioxidants (vitamin A)
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2
Q

What is the first step in the synthesis of fatty acids? Which enzyme catalyzes this step?

A
  • Formation of Malonyl-CoA from Acetyl-CoA

- Acetyl-CoA carboxylase (ACC)

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3
Q

Does Acetyl-CoA carboxylase (ACC) require energy?

A

Yes

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4
Q

How is Malonyl-CoA formed?

A
  • CO2 is added to biotin
  • Conformational change: biotin shifts from biotin carboxylase to trans carboxylase
  • CO2 is added to Acetyl-CoA, converting it to Malonyl-CoA
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5
Q

What is the second step in the synthesis of fatty acids? Which enzyme catalyzes this step?

A
  • Addition of 2-carbons to fatty acyl chains

- Fatty acid synthase

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6
Q

Which reactions occur on fatty acid synthase (in order)?

A

1) Condensation
2) Reduction
3) Dehydration
3) Reduction

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7
Q

How does Malonyl-CoA attach to fatty acid synthase?

A

By a thiol (SH) group, attached to Lysine in the ACP moiety

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8
Q

To which domain on the fatty acid synthase does Malonyl-CoA attach itself?

A

ALWAYS attaches on the ACP domain

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9
Q

What is on the KS domain of fatty acid synthase? What happens to it?

A
  • Acetyl-CoA

- Structure is brought to ACP to get elongated

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10
Q

Where does the elongated FA chain go?

A

Brought BACK to the KS domain

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11
Q

Where does elongation occur?

A
  • OCCURS in the ACP domain

- Brought back to the KS domain AFTER

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12
Q

What does the reduction reaction do in fatty acid synthase?

A

Adds hydrogens to the carbons through NADPH

- In the second reduction, it creates a CH2-CH2 bond

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13
Q

At which residue does the growth of the fatty acid chain occur?

A

On the lysine

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14
Q

What fatty acid does fatty acid synthase typically synthesize?

A

Palmitate (16:0)

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15
Q

Where are long fatty acid chains produced?

A
  • In the ER

- In the mitochondria

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16
Q

What is the precursor for longer FA chains?

A

Palmitate

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17
Q

What is the precursor for unsaturated fatty acids?

A

Palmitate and stearate

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18
Q

How are palmitate and stearate desaturated?

A
  • By Fatty acyl-CoA desaturase

- Adds double bonds by an oxidative reaction (removes hydrogens)

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19
Q

Where are the double bonds on palmitoleate? What about oleate? How many carbons do they have?

A
  • Palmitoleate (16:1)
  • Oleate (18:1)
  • Double bonds are at C9-C10
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20
Q

Which fatty acid cannot be synthesized in mammals?

A
  • Linoleate (18:2)
  • Double bonds at 9 and 12
  • It is essential, must be eaten
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21
Q

What is arachidonate synthesized from?

A

Linoleate

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22
Q

Can arachidonate be synthesized by mammals?

Study These Flashcards
A

Yes, but it requires linoleate (which can’t)

23
Q

What is the rate-limiting enzyme in the biosynthesis of fatty acids?

Study These Flashcards
A

Acetyl-CoA carboxylase

24
Q

What is Acetyl-CoA carboxylase inhibited by?

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A

Phosphorylation, which is regulated by the hormones epinephrine and glucagon

25
What is the feedback inhibitor of Acetyl-CoA carboxylase?
Palmitoyl-CoA
26
What is an activator of Acetyl-CoA carboxylase?
Citrate
27
What does catabolism of fatty acids produce? Where does it occur?
- Produces Acetyl-CoA and electron donors (NADH) | - Takes place in the mitochondria
28
What does anabolism of fatty acids produce? Where does it occur?
- Requires Acetyl-CoA, Malonyl-CoA, and electron donors (NADPH) - Takes place in the cytosol
29
What makes Acetyl-CoA be destined for B-oxidation?
When it is brought back into the mitochondria through carnitation
30
What makes Acetyl-CoA be destined for fatty acid synthesis?
When it is converted to Malonyl-CoA
31
_____________ inhibits all reactions towards B-oxidation.
Malonyl-CoA
32
How does high levels of glucose regulate fatty acid synthesis/breakdown?
- Sufficient energy; release of glucose - Signals to hormone-dependent phosphatase to remove a phosphate group of ACC - Activates ACC and FA synthesis
33
How does low levels of glucose regulate fatty acid synthesis/breakdown?
- Glucagon (GPCR) leads to the activation of PKA through cyclic AMP - PKA phosphorylates ACC, which inactivates it - Inactivation of FA synthesis
34
What is the source of Acetyl-CoA for the synthesis of fatty acids?
- NOT B-oxidation - Pyruvate carboxylation - AA catabolism
35
How does Acetyl-CoA escape from the matrix of the mitochondria?
- Acetyl-CoA is added to Oxaloacetate - Citrate synthase in the TCA cycle makes citrate out of it - Transporter for citrate transports it from the matrix to the cytoplasm - Citrate lyase in the cytoplasm converts it to Acetyl-CoA and oxaloacetate
36
What happens to the oxaloacetate in the cytoplasm produced by citrate lyase?
- Oxaloacetate gets converted to Malate by Malate dehydrogenase - Malate is transported to the matrix through the malate-a-ketoglutarate transporter - Or, malate is converted to pyruvate in the cytoplasm - Pyruvate can go into the mitochondria easily through transporters
37
What are the two steps to the biosynthesis of triacylglycerols?
1) Glycerol-3-phosphate to phosphatidic acid | 2) Phosphatidic acid to TG
38
Which enzyme catalyzes glycerol-3-phosphate to phosphatidic acid?
Acyl transferase
39
What does acyl transferase do?
- Transfers two fatty acid chains (acyl chains) | - One phosphate still remains, which makes it phosphatidic acid
40
What can phosphatidic acid become? (2)
1) Synthesized to a glycerophospholipid by adding a head group 2) Phosphate is removed, and one more acyl group is added to form a TG
41
Which enzymes catalyze phosphatidic acid to TG?
1) Phosphatidic acid phosphatase (removes phosphate) | 2) Acyl transferase (adds a FA)
42
What promotes the synthesis of TG? How?
- Insulin | - Activation of acyl transferase
43
Where does the biosynthesis of cholesterol occur?
- In the cytoplasm/microsomes
44
What are the steps of the biosynthesis of cholesterol?
1) Condensation 2) Phosphorylation 3) Polymerization 4) Cyclization
45
In the biosynthesis of cholesterol, what are the intermediates produced following condensation?
- Converts acetate to HMG-CoA by HMG-CoA synthase | - Converts HMG-CoA to Mevalonate by HMG-CoA reductase
46
Where is HMG-COA synthase present? What is it used for?
1) Mitochondria: ketone body synthesis | 2) Cytoplasm: biosynthesis of cholesterol
47
What happens during polymerization and cyclization in the biosynthesis of cholesterol?
Polymerization: straight chains Cyclization: straight chains --> cyclic rings
48
What is the rate-limiting enzyme in cholesterol synthesis?
HMG-CoA reductase
49
How does AMP-dependent protein kinase affect cholesterol synthesis?
- When AMP rises, kinase phosphorylates the enzyme | - Decreases cholesterol synthesis
50
How do glucagon and epinephrine affect cholesterol synthesis?
- Cascades lead to phosphorylation | - Decreases cholesterol synthesis
51
How does insulin affect cholesterol synthesis?
- Cascades lead to dephosphorylation | - Increases cholesterol synthesis
52
What does Insig mean? What is its function in cholesterol synthesis?
- Insulin-Induced Gene Protein | - Senses cholesterol levels
53
What does Insig trigger when cholesterol levels are high?
- Triggers ubiquination of HMG-CoA reductase - Ubiquination triggers protein degradation - Decreases cholesterol synthesis

2) Biochemistry II (23 decks)

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