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Biochemistry Endterm > FA Synthesis > Flashcards

FA Synthesis Flashcards

1
Q

What triggers FA synthesis?

A

High glucose metabolism ➡️ high generation of acetyl coA in mitochondria triggers it

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2
Q

What serves as major precursor of Fatty acid synthesis?

A

Acetyl coa

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3
Q

What problem do we face in FA synthesis?

A

Transporting acetyl coa from mitochondria to cytoplasm

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4
Q

Where does fa synthesis occur?

A

Cytoplasm

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5
Q

Where is acetyl coa found?

A

Mitochondria

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6
Q

What is the problem in transporting acetly CoA from mitochondrial matrix to cytoplasm ?

A

The CoA portion of acetly CoA can not cross out from the mitochondrial membrane to cytoplasm.

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7
Q

What is the solution to the problem that acetyl coa cannot cross?

A

Acetyl coA condenses with oxaloacetate producing citrate

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8
Q

What enzyme is involved in the condensation of oxaloacetate and acetyl CoA to form citrate?

A

citrate synthase (CS).

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9
Q

AcetylCoAcondenseswith oxaloacetate producing citrate by citrate synthase (CS). What happens at the same time?

A

The high level of acetyl CoA also activates pyruvate carboxylase (PC).

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10
Q

Whats the role of Pyruvate Carboxylase or PC?

A

converts pyruvate into oxaloacetate, which is needed for condensing it with acetyl CoA and producing citrate.

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11
Q

What happens once citrate is formed in the mitochondria?

A

Its transported to cytoplasm by citrate transporter

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12
Q

Once citrate is in the cytosol what happens?

A

citrate is converted back into acetly-CoA and oxaloacetate

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13
Q

In cytosol, the citrate is converted back into acetly-CoA and oxaloacetate by ______ _______using _____ as a substrate

A

citrate lyase (CL) using CoA as substrate.

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14
Q

After split of citrate what happens to Acetyl coA part?

A

will be used for fatty acid synthesis.

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15
Q

After split of citrate what happens to oxaloacetate part?

A

will be converted into malate and then to pyruvate

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16
Q

What is the fate of pyruvate once its synthesized in the cytoplasm?

A

Pyruvate enters back into mitochondria and is again converted into acetyl coA. The cycle then continues

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17
Q

What is the first thing that will happen to acetyl CoA following the split of citrate?

A

It will be converted into malonyl coA by Acetyl CoA Carboxylase

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18
Q

_________: The acetyl CoA is first converted into malonyl CoA by Acetyl CoA carboxylase (ACC) enzyme.

A

In cytoplasm

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19
Q

In cytoplasm: The _________ is first converted into malonyl CoA by Acetyl CoA carboxylase (ACC) enzyme.

A

acetyl CoA

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20
Q

In cytoplasm: The acetyl CoA is first converted into_________ by Acetyl CoA carboxylase (ACC) enzyme.

A

Malonyl CoA

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21
Q

In cytoplasm: The acetyl CoA is first converted into malonyl CoA by_____________enzyme.

A

Acetyl CoA carboxylase (ACC)

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22
Q

What is the function of ACC

A

transfers a carboxyl (COO) group to acetly CoA and produces malonyl CoA.

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23
Q

What is carboxylation?

A

Transfer or adding CO2

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24
Q

Whats the role of biotin in FA synthesis?

A

acts as a co-enzyme and helps for carboxylation reaction.

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25
Q

Biotin carries ___ in one side and binds other side with a ______ _______ of the ACC enzyme.

A

CO2

Lysyl residue

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26
Q

Biotin carries CO2 in one side and binds other side with a lysyl residue of the ___ ________.

A

ACC enzyme.

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27
Q

Whats the rate limiting enzyme of FA synthesis?

A

ACC

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28
Q

What are the different ways ACC can be regulated?

A

by Citrate level
by fatty acids
by Glucose-6-Phosphate
by hormones

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29
Q

Explain how ACC is regulated by citrate level

A

When acetyl CoA ⬆️( high glucose)
➡️ acetyl coA ➡️ citrate

Citrate transported: mito ➡️ cyto

Then citrate allosterically binds with inactive ACC➡️ active ACC

Active ACC: acetyl CoA ➡️ malonyl CoA

Malonyl CoA used for FA synthesis

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30
Q

What does an increase in citrate level result in ( inhibit or stimulate)?

A

Stimulate FA synthesis

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31
Q

Explain Regulation of Acetyl CoA carboxylase by fatty acids

A

When glucose level ⬇️

• The fatty acids(Ex:palmitolyCoA) allosterically binds with active ACC polymers and converts them into inactivate dimers (depolymerization).

Fatty acid synthesis is inhibited.

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32
Q

Regulation of Acetyl CoA carboxylase by fatty acids stimulates or inhibits?

A

Negative feed back mechanism therefore inhibit

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33
Q

Explain Regulation of Acetyl CoA carboxylase by Glucose-6-Phosphate

A
  • High glucose ➡️High glycolysis➡️High Glucose-6-Phosphate (G6P) metabolite.
  • High G6P triggers the translocation of transcription factor Carbohydrate Responsive Element Binding Proteins (ChREBP a/b) from cytoplasm to nucleus.
  • In nuclease, ChREBPs binds on the Carbohydrate Responsive Element (ChoRE) of the ACC gene and triggers its expression.
  • ACC converts acetly CoA to malonyl CoA
  • Molonyl CoA activates fatty acid synthesis
  • Thus high glucose activates the expression of ACC through its metabolite, G6P.
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34
Q

True or false. High carbohydrate diet increases the synthesis of ACC.

A

True

35
Q

What does high G6P trigger?

A

High G6P triggers the translocation of transcription factor Carbohydrate Responsive Element Binding Proteins (ChREBP a/b) from cytoplasm to nucleus.

36
Q

What happens to ChREBPs in nucleus?

A

ChREBPs binds on the Carbohydrate Responsive Element (ChoRE) of the ACC gene and triggers its expression

37
Q

True or false. high glucose inhibits the expression of ACC through its metabolite, G6P.

A

False. high glucose activates the expression of ACC through its metabolite, G6P.

38
Q

Explain Regulation of Acetyl CoA carboxylase by hormones ( insulin)

A

⬆️glucose ➡️insulin➡️activate protein phosphatase➡️ PP dephosphorylates and activates ACC➡️ converts Acetyl coa to malonyl CoA ➡️ Fa synthesis starts

39
Q

Regulation of Acetyl CoA carboxylase by hormones ( glucagon)

A

⬇️Glucose ➡️Glucagon and epinephrine➡️ActivatesAMPK kinase
➡️AMPK kinase phosphorylates
and activates AMPK ➡️Activated AMPK phosphorylates and inactivates ACC ➡️FA synthesis stops

40
Q

What step’s following the conversion of acetyl coa to malonyl coa?

A

Conversion of Malonyl CoA to fatty acids ( palmitic acid) by Fatty acid synthase

41
Q

What is Fatty Acid Synthase (FAS) ?

A

FAS is a dimer of two identical monomer of polypeptides

42
Q

What type of enzyme is Fatty Acid Synthase (FAS) ?

A

Holoenzyme

43
Q

Each monomer of FAS consists of how many domains?

A

8 domains / polypeptides

44
Q

Each monomer of FAS consists of what domains?

A 
(KS)
(AT)
(MT)
(HD)
(ER)
(KR)
(TE)
(ACP)
45
Q

Two monomers create…

A

a head-to-tail dimer structure.

46
Q

KS

A

3-Ketoacyl-ACP synthase

47
Q

AT

A

Acetyl CoA-ACP transacylase

48
Q

MT

A

Malonyl CoA-ACP transacylase

49
Q

HD

A

3-Hydroxyacyl-ACP dehydratase

50
Q

ER

A

Enoyl-ACP reductase

51
Q

KR

A

3-Ketoacyl-ACP reductase

52
Q

TE

A

Thioestrase

53
Q

ACP

A

Acyl carrier protein

54
Q

Although each monomer ( structural division) contains all ..

A

necessary enzymes for FA synthesis, they can’t synthesize FA.

55
Q

Though each monomer (structural division) contains all the necessary enzymes for FA synthesis, they can’t synthesize FA.Therefore,…

A

two monomers share half of each monomer to form a functional division for synthesizing FA

56
Q

What does a functional division of FAS consist of?

A

one half of one monomer interacting with the half of another monomer.

57
Q

Whats the role of the ACP domain?

A

helps receiving the incoming Carbons and elongating the FA chain synthesis.

58
Q

FA dimer synthesizes ___ ___ simultaneously.

A

2 FAs

59
Q

Palmitic acid synthesis cycle 1 steps

A
  1. acetyl coA attsches to ACP of FAS and releases CoA
  2. The 2 carbons fragment is transferred to a Cysteine (CYS) residue of the KS.
  3. Next, the malonyl CoA (3 carbons) is attached with ACP releasing a CoA.
  4. Condensation
  5. Reduction
  6. Dehydration
  7. Reduction
60
Q

What is the first step of palmitic acid synthesis? C1

A

First, an acetly CoA is attached with ACP domain of FAS releasing a CoA.

61
Q

What is the first step of palmitic acid synthesis catalyzed by?

A

AT of FAS

62
Q

What is the second step of palmitic acid synthesis?

A

The 2 carbons fragment is transferred to a Cysteine (CYS) residue of the 3-Ketoacyl-ACP synthase (KS)

63
Q

What is the third step of palmitic acid synthesis?

A

the malonyl CoA (3 carbons) is attached with ACP releasing a CoA.

64
Q

What is the third step of palmitic acid synthesis catalyzed by?

A

MT of FAS

65
Q

What is the fourth step of palmitic acid synthesis ?

A

Condensation: Acetly group on the cysteine residue of KS domain condenses with malonly group on ACP domain releasing CO2. It results into a 4 carbon chain on the ACP domain.

66
Q

Condensation: _____ on the cysteine residue of _________ condenses with malonyl group on _______ releasing CO2. It results into a _ carbon chain on the ___ _______.

A 
Acetly group
KS domain
ACP domain 
4
ACP domain
67
Q

What is the fourth step of palmitic acid synthesis catalyzed by?

A

KS

68
Q

What is the fifth step of palmitic acid synthesis ?

A

Keto group is reduced to an alcohol by KR domain of FAS. NADPH is oxidized to NADP.

69
Q

What is the sixth step of palmitic acid synthesis ?

A

Water molecule is removed creating a trans double bonds between carbons 2 and 3.

70
Q

What is the sixth step of palmitic acid synthesis catalyzed by?

A

HD domain of FAS.

71
Q

What is the seventh step of palmitic acid synthesis ?

A

Reduction: Finally, the double bond is reduced by the ER domain of FAS. NADPH is oxidized to NADP.

72
Q

At the end of cycle-1 (involving 7 steps), FAS …

A

produces a 4C containing saturated butyric acid (Butyryl-ACP).

73
Q

Cycle-2 is repeated beginning from____

A

Step2

74
Q

What happens in step 2 of cycle 2?

A

Transfer of the 4C butyryl unit from the ACP to the Cys residue of KS domain

75
Q

What happens in step 3 of cycle 2?

A

Attachment of Malonyl CoA to ACP domain

76
Q

What happens in step 4 of cycle 2?

A

Condensation of butyryl and malonly releases CO2

and yields a 6C containing fatty acid chain.

77
Q

What happens in step 5 of cycle 2?

A

Reduction of carbonyl group (keto) at the third Carbon from the Sulfur group.

78
Q

What happens in step 6 and 7 of cycle 2?

A

Dehydration and reduction

79
Q

What happens at the end of cycle 2?

A

FAS adds 2 more carbons to the 4C butyryl and produces a

6 carbon containing fatty acid chain, hexanoyl-ACP.

80
Q

Cycles 3 to 7 (5 more cycles) will be repeated in the same pattern starting from the steps-.. In each cycle, FAS adds ..

A

2 to 7.

2C and elongates FA chain

81
Q

Where are the 16C of palmitic acid obtained from?

A

First 2C are obtained from the acetyl CoA (step-1 of cycle-1).
• Remaining 14C are obtained from malonyl CoA (7cycles x 2C = 14C).

82
Q

Finally step of palmitic acid synthesis.

A

palmitoyl thioesterase (TE) of FAS cleaves the thioester bond and releases a saturated palmitate (16C) from the ACP domain using one H2O molecule.

83
Q

Of the 7 cycles used in synthesizing a 16C palmitic acid
Cycle 1: …
Cycle 2:…

A
  • Cycle-1:
  • FAS adds 4 carbons (2C from Acetyl Co A + 2C from Malonyla CoA).
  • Cycles 2-7:
  • FAS adds only 2 carbons from malonyl CoA.

Biochemistry Endterm (1 decks)

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