Fatty Acid and Triacylglycerol Metabolism Flashcards

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
How do high-fat diets, fasting ad glucagon levels regulate Acetyl CoA Carboxylase long term?
Lead to decreased synthesis (down regulation, repression) resulting in decreased synthesis of FA
26
Which form of Fatty Acid Synthase is the fully functional form?
Dimeric
27
How does insulin effect Fatty Acid Synthase?
Upregulates the amount of enzyme expressed
28
In the first reaction of FA synthesis, Acetyl CoA is added to a ______ group of which domain of FAS?
``` Cysteine-SH group; Condensing Enzyme (CE) domain ```
29
What is added in the second reaction of FA synthesis?
Malonyl CoA
30
Which group is Malonyl CoA added to in the second step of FA synthesis?
ACP sulfhydryl group | ACP= acyl carrier peptide
31
What occurs during the 3rd reaction of FA synthesis?
Acetyl group is transferred to the Malonyl Group with the release of carbon dioxide
32
Regarding the 4th step of FA synthesis, the _______ is _______ to a ______ by the ________ activity.
Keto group; Reduced; Hydroxyl group; Beta-ketoacyl reductase
33
Regarding the 5th reaction, what is dehydrated to form a trans-monounsaturated fatty acyl group?
Beta-hydroxybutyryl-ACP
34
What occurs in the 6th reaction of Fatty Acid synthesis
An acyl group is converted to a butyryl group | Then, butyryl group is transferred from ACP sulfhydryl group to CE sulfhydryl
35
What occurs after step 6 in FA synthesis?
The butyryl group is now ready to condense with a new malonyl group (step 3) to repeat the process
36
Regarding FA Synthesis, Once the fatty acyl group reaches its final carbon chain length, what occurs in step 7?
Thioesterase activity hydrolyses it, forming final free form.
37
What modifications are typically made to produce variety in fatty acids?
- chain elongation to give longer fatty acids | - desaturation, giving unsaturated fatty acids
38
Where does chain elongation of fatty acids primarily occur?
Membranes of ER and involves addition of malonyl CoA to palmitate.
39
Where is the minor elongation pathway of fatty acids and how does it occur?
Mitochondria; | Reversal of B-oxidation.
40
What introduces sites of unsaturation (double bonds) in fatty acids?
Fatty acyl-CoA desaturases
41
In the fatty acid desaturation system, what positions are doubles bonds introduced by fatty acyl-CoA desaturases?
5, 6 or 9
42
Why are linoleate and linolenate considered essential fatty acids?
Because they have unsaturations beyond carbon 9
43
What 3 enzymes are involved in the fatty acid desaturase system (an electron transport system in the ER)
1) cytochrome b5 2) desaturase 3) NADPH-cytochrome b5 reductase
44
What are the substrates in phosphatic acid synthesis?
DHAP--> Glycerol-3-Phosphate --> Monoacylglycerol-3-phosphate---> Phosphatic Acid
45
DHAP is converted to Glycerol-3-phosphate using which enzyme?
Glycerol-3-phosphate
46
What are the substrates of TAG synthesis?
Phosphatic acid --> 1,2-Diacylglycerol--> TAG