Fatty Acid and Triacylglycerol Metabolism Flashcards

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1
Q

What are the two main sites of fatty acid de novo synthesis?

A

1) Liver after a carbohydrate rich meal

2) Lactating mammary gland

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2
Q

What can be achieved by fatty acid de novo synthesis in the liver after a carbohydrate rich meal?

A

Fatty acid de novo synthesis in the liver reduces the high blood glucose level
after a carbohydrate-rich mean and it also provides fatty acids for eventual
storage in TAGs in fat cells.

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3
Q

Which metabolic condition leads to high citrate levels in liver mitochondria?

A

A high carbohydrate diet leads to increased citrate in liver mitochondria

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4
Q

What happens to the citrate in liver mitochondria after a carb rich meal

A

High citrate levels in liver mitochondria lead to transfer of citrate into the cytosol

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5
Q

Describe the cellular location of citrate lyase and describe the irreversible reaction catalyzed by this enzyme.

A

-Citrate lyase is found in cytosol.
-Citrate and CoA and ATP are the substrates and products are acetyl CoA ,
oxaloacetate , ADP and Pi

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6
Q

Describe the cellular location and the reaction catalyzed by the malic enzyme.

A
  • The malic enzyme is found in liver cytosol.

- Malate and NADP+ are substrates and products are pyruvate, CO2 and NADPH

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7
Q

What is the dietary precursor to arachidonic acid?

A

Linoleic acid

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8
Q

Biosynthesis of fatty acids most likely occurs in which state?

A

Well-fed state

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9
Q

Where does Acetyl CoA produced in mitochondria come from?

A
  • oxidation of pyruvate (PDH complex)
  • Degradation of fatty acids
  • Degradation of ketone bodies
  • Degradation of amino acids
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10
Q

What happens when ATP is high in the mitochondria which causes Acetyl CoA to be converted to citrate?

A

Isocitrate dehydrogenase is inhibited

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11
Q

What is Acetyl CoA converted to for transport in the cytosol?

A

Citrate

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12
Q

Once in the cytosol, what enzyme converts Citrate into Acetyl CoA and Oxaloacetate?

A

ATP-Citrate lyase

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13
Q

Which enzyme produces NADPH in order to be used in Fatty Acid synthesis?

A

Malic enzyme

converts malate to pyruvate

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14
Q

Which enzyme catalyzes the first committed step of fatty acid biosynthesis?

A

Acetyl CoA Carboxylase (ACC)

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15
Q

What is the rate-limiting enzyme for fatty acid synthesis?

A

Acetyl-CoA Carboxylase

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16
Q

Which cofactor does Acetyl CoA Carboxylase need?

A

Biotin

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17
Q

Acetyl CoA Carboxylase requires how many ATP molecules per malonyl-coA formed?

A

1 ATP

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18
Q

The enzyme Acetyl CoA Carboxylase converts _____ to _____

A

Acetyl CoA

Malonyl CoA

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19
Q

What two molecules are used in short term allosteric regulation of Acetyl CoA Carboxylase?

A

Citrate

Palmitoyl CoA

20
Q

How does citrate allosterically regulate Acetyl CoA Carboxylase?

A

Citrate shifts the polymer - monomer equilibrium towards polymer formation –> activation

21
Q

How does Palmitoyl CoA allosterically regulate Acetyl CoA Carboxylase?

A

Palmitoyl CoA shifts the equilibrium toward monomer formation –> inhibition

22
Q

What contributes to short term HORMONAL regulation of Acetyl CoA Carboxylase?

A

Glucagon
Epinephrine
Norepinephrine

23
Q

How do glucagon, epinephrine and norepinephrine act upon Acetyl CoA Carboxylase?

A

Trigger cAMP dependent phosphorylation of enzyme (through activation of AMPK) that shifts the equilibrium toward monomer formation (inactive form).

24
Q

How does high carb, fat free diet lead to Long term regulation of Acetyl CoA Carboxylase.

A

Up-regulation/ induction of ACC resulting in increased synthesis of FA

25
Q

How do high-fat diets, fasting ad glucagon levels regulate Acetyl CoA Carboxylase long term?

A

Lead to decreased synthesis (down regulation, repression) resulting in decreased synthesis of FA

26
Q

Which form of Fatty Acid Synthase is the fully functional form?

A

Dimeric

27
Q

How does insulin effect Fatty Acid Synthase?

A

Upregulates the amount of enzyme expressed

28
Q

In the first reaction of FA synthesis, Acetyl CoA is added to a ______ group of which domain of FAS?

A
Cysteine-SH group;
Condensing Enzyme (CE) domain
29
Q

What is added in the second reaction of FA synthesis?

A

Malonyl CoA

30
Q

Which group is Malonyl CoA added to in the second step of FA synthesis?

A

ACP sulfhydryl group

ACP= acyl carrier peptide

31
Q

What occurs during the 3rd reaction of FA synthesis?

A

Acetyl group is transferred to the Malonyl Group with the release of carbon dioxide

32
Q

Regarding the 4th step of FA synthesis, the _______ is _______ to a ______ by the ________ activity.

A

Keto group;
Reduced;
Hydroxyl group;
Beta-ketoacyl reductase

33
Q

Regarding the 5th reaction, what is dehydrated to form a trans-monounsaturated fatty acyl group?

A

Beta-hydroxybutyryl-ACP

34
Q

What occurs in the 6th reaction of Fatty Acid synthesis

A

An acyl group is converted to a butyryl group

Then, butyryl group is transferred from ACP sulfhydryl group to CE sulfhydryl

35
Q

What occurs after step 6 in FA synthesis?

A

The butyryl group is now ready to condense with a new malonyl group (step 3) to repeat the process

36
Q

Regarding FA Synthesis, Once the fatty acyl group reaches its final carbon chain length, what occurs in step 7?

A

Thioesterase activity hydrolyses it, forming final free form.

37
Q

What modifications are typically made to produce variety in fatty acids?

A
  • chain elongation to give longer fatty acids

- desaturation, giving unsaturated fatty acids

38
Q

Where does chain elongation of fatty acids primarily occur?

A

Membranes of ER and involves addition of malonyl CoA to palmitate.

39
Q

Where is the minor elongation pathway of fatty acids and how does it occur?

A

Mitochondria;

Reversal of B-oxidation.

40
Q

What introduces sites of unsaturation (double bonds) in fatty acids?

A

Fatty acyl-CoA desaturases

41
Q

In the fatty acid desaturation system, what positions are doubles bonds introduced by fatty acyl-CoA desaturases?

A

5, 6 or 9

42
Q

Why are linoleate and linolenate considered essential fatty acids?

A

Because they have unsaturations beyond carbon 9

43
Q

What 3 enzymes are involved in the fatty acid desaturase system (an electron transport system in the ER)

A

1) cytochrome b5
2) desaturase
3) NADPH-cytochrome b5 reductase

44
Q

What are the substrates in phosphatic acid synthesis?

A

DHAP–> Glycerol-3-Phosphate –> Monoacylglycerol-3-phosphate—> Phosphatic Acid

45
Q

DHAP is converted to Glycerol-3-phosphate using which enzyme?

A

Glycerol-3-phosphate

46
Q

What are the substrates of TAG synthesis?

A

Phosphatic acid –> 1,2-Diacylglycerol–> TAG