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2) Biochemistry II > Lipid Biosynthesis > Flashcards

Lipid Biosynthesis Flashcards

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?

A

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

23
Q

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

A

Acetyl-CoA carboxylase

24
Q

What is Acetyl-CoA carboxylase inhibited by?

A

Phosphorylation, which is regulated by the hormones epinephrine and glucagon

25
Q

What is the feedback inhibitor of Acetyl-CoA carboxylase?

A

Palmitoyl-CoA

26
Q

What is an activator of Acetyl-CoA carboxylase?

A

Citrate

27
Q

What does catabolism of fatty acids produce? Where does it occur?

A
  • Produces Acetyl-CoA and electron donors (NADH)

- Takes place in the mitochondria

28
Q

What does anabolism of fatty acids produce? Where does it occur?

A
  • Requires Acetyl-CoA, Malonyl-CoA, and electron donors (NADPH)
  • Takes place in the cytosol
29
Q

What makes Acetyl-CoA be destined for B-oxidation?

A

When it is brought back into the mitochondria through carnitation

30
Q

What makes Acetyl-CoA be destined for fatty acid synthesis?

A

When it is converted to Malonyl-CoA

31
Q

_____________ inhibits all reactions towards B-oxidation.

A

Malonyl-CoA

32
Q

How does high levels of glucose regulate fatty acid synthesis/breakdown?

A
  • Sufficient energy; release of glucose
  • Signals to hormone-dependent phosphatase to remove a phosphate group of ACC
  • Activates ACC and FA synthesis
33
Q

How does low levels of glucose regulate fatty acid synthesis/breakdown?

A
  • Glucagon (GPCR) leads to the activation of PKA through cyclic AMP
  • PKA phosphorylates ACC, which inactivates it
  • Inactivation of FA synthesis
34
Q

What is the source of Acetyl-CoA for the synthesis of fatty acids?

A
  • NOT B-oxidation
  • Pyruvate carboxylation
  • AA catabolism
35
Q

How does Acetyl-CoA escape from the matrix of the mitochondria?

A
  • 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
Q

What happens to the oxaloacetate in the cytoplasm produced by citrate lyase?

A
  • 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
Q

What are the two steps to the biosynthesis of triacylglycerols?

A

1) Glycerol-3-phosphate to phosphatidic acid

2) Phosphatidic acid to TG

38
Q

Which enzyme catalyzes glycerol-3-phosphate to phosphatidic acid?

A

Acyl transferase

39
Q

What does acyl transferase do?

A
  • Transfers two fatty acid chains (acyl chains)

- One phosphate still remains, which makes it phosphatidic acid

40
Q

What can phosphatidic acid become? (2)

A

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
Q

Which enzymes catalyze phosphatidic acid to TG?

A

1) Phosphatidic acid phosphatase (removes phosphate)

2) Acyl transferase (adds a FA)

42
Q

What promotes the synthesis of TG? How?

A
  • Insulin

- Activation of acyl transferase

43
Q

Where does the biosynthesis of cholesterol occur?

A
  • In the cytoplasm/microsomes
44
Q

What are the steps of the biosynthesis of cholesterol?

A

1) Condensation
2) Phosphorylation
3) Polymerization
4) Cyclization

45
Q

In the biosynthesis of cholesterol, what are the intermediates produced following condensation?

A
  • Converts acetate to HMG-CoA by HMG-CoA synthase

- Converts HMG-CoA to Mevalonate by HMG-CoA reductase

46
Q

Where is HMG-COA synthase present? What is it used for?

A

1) Mitochondria: ketone body synthesis

2) Cytoplasm: biosynthesis of cholesterol

47
Q

What happens during polymerization and cyclization in the biosynthesis of cholesterol?

A

Polymerization: straight chains
Cyclization: straight chains –> cyclic rings

48
Q

What is the rate-limiting enzyme in cholesterol synthesis?

A

HMG-CoA reductase

49
Q

How does AMP-dependent protein kinase affect cholesterol synthesis?

A
  • When AMP rises, kinase phosphorylates the enzyme

- Decreases cholesterol synthesis

50
Q

How do glucagon and epinephrine affect cholesterol synthesis?

A
  • Cascades lead to phosphorylation

- Decreases cholesterol synthesis

51
Q

How does insulin affect cholesterol synthesis?

A
  • Cascades lead to dephosphorylation

- Increases cholesterol synthesis

52
Q

What does Insig mean? What is its function in cholesterol synthesis?

A
  • Insulin-Induced Gene Protein

- Senses cholesterol levels

53
Q

What does Insig trigger when cholesterol levels are high?

A
  • Triggers ubiquination of HMG-CoA reductase
  • Ubiquination triggers protein degradation
  • Decreases cholesterol synthesis

2) Biochemistry II (23 decks)

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