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FA Synthesis Flashcards

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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
Biotin carries ___ in one side and binds other side with a ______ _______ of the ACC enzyme.
CO2 | Lysyl residue
26
Biotin carries CO2 in one side and binds other side with a lysyl residue of the ___ ________.
ACC enzyme.
27
Whats the rate limiting enzyme of FA synthesis?
ACC
28
What are the different ways ACC can be regulated?
by Citrate level by fatty acids by Glucose-6-Phosphate by hormones
29
Explain how ACC is regulated by citrate level
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
30
What does an increase in citrate level result in ( inhibit or stimulate)?
Stimulate FA synthesis
31
Explain Regulation of Acetyl CoA carboxylase by fatty acids
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.
32
Regulation of Acetyl CoA carboxylase by fatty acids stimulates or inhibits?
Negative feed back mechanism therefore inhibit
33
Explain Regulation of Acetyl CoA carboxylase by Glucose-6-Phosphate
* 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.
34
True or false. High carbohydrate diet increases the synthesis of ACC.
True
35
What does high G6P trigger?
High G6P triggers the translocation of transcription factor Carbohydrate Responsive Element Binding Proteins (ChREBP a/b) from cytoplasm to nucleus.
36
What happens to ChREBPs in nucleus?
ChREBPs binds on the Carbohydrate Responsive Element (ChoRE) of the ACC gene and triggers its expression
37
True or false. high glucose inhibits the expression of ACC through its metabolite, G6P.
False. high glucose activates the expression of ACC through its metabolite, G6P.
38
Explain Regulation of Acetyl CoA carboxylase by hormones ( insulin)
⬆️glucose ➡️insulin➡️activate protein phosphatase➡️ PP dephosphorylates and activates ACC➡️ converts Acetyl coa to malonyl CoA ➡️ Fa synthesis starts
39
Regulation of Acetyl CoA carboxylase by hormones ( glucagon)
⬇️Glucose ➡️Glucagon and epinephrine➡️ActivatesAMPK kinase ➡️AMPK kinase phosphorylates and activates AMPK ➡️Activated AMPK phosphorylates and inactivates ACC ➡️FA synthesis stops
40
What step’s following the conversion of acetyl coa to malonyl coa?
Conversion of Malonyl CoA to fatty acids ( palmitic acid) by Fatty acid synthase
41
What is Fatty Acid Synthase (FAS) ?
FAS is a dimer of two identical monomer of polypeptides
42
What type of enzyme is Fatty Acid Synthase (FAS) ?
Holoenzyme
43
Each monomer of FAS consists of how many domains?
8 domains / polypeptides
44
Each monomer of FAS consists of what domains?
``` (KS) (AT) (MT) (HD) (ER) (KR) (TE) (ACP) ```
45
Two monomers create…
a head-to-tail dimer structure.
46
KS
3-Ketoacyl-ACP synthase
47
AT
Acetyl CoA-ACP transacylase
48
MT
Malonyl CoA-ACP transacylase
49
HD
3-Hydroxyacyl-ACP dehydratase
50
ER
Enoyl-ACP reductase
51
KR
3-Ketoacyl-ACP reductase
52
TE
Thioestrase
53
ACP
Acyl carrier protein
54
Although each monomer ( structural division) contains all ..
necessary enzymes for FA synthesis, they can’t synthesize FA.
55
Though each monomer (structural division) contains all the necessary enzymes for FA synthesis, they can’t synthesize FA.Therefore,…
two monomers share half of each monomer to form a functional division for synthesizing FA
56
What does a functional division of FAS consist of?
one half of one monomer interacting with the half of another monomer.
57
Whats the role of the ACP domain?
helps receiving the incoming Carbons and elongating the FA chain synthesis.
58
FA dimer synthesizes ___ ___ simultaneously.
2 FAs
59
Palmitic acid synthesis cycle 1 steps
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
What is the first step of palmitic acid synthesis? C1
First, an acetly CoA is attached with ACP domain of FAS releasing a CoA.
61
What is the first step of palmitic acid synthesis catalyzed by?
AT of FAS
62
What is the second step of palmitic acid synthesis?
The 2 carbons fragment is transferred to a Cysteine (CYS) residue of the 3-Ketoacyl-ACP synthase (KS)
63
What is the third step of palmitic acid synthesis?
the malonyl CoA (3 carbons) is attached with ACP releasing a CoA.
64
What is the third step of palmitic acid synthesis catalyzed by?
MT of FAS
65
What is the fourth step of palmitic acid synthesis ?
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
Condensation: _____ on the cysteine residue of _________ condenses with malonyl group on _______ releasing CO2. It results into a _ carbon chain on the ___ _______.
``` Acetly group KS domain ACP domain 4 ACP domain ```
67
What is the fourth step of palmitic acid synthesis catalyzed by?
KS
68
What is the fifth step of palmitic acid synthesis ?
Keto group is reduced to an alcohol by KR domain of FAS. NADPH is oxidized to NADP.
69
What is the sixth step of palmitic acid synthesis ?
Water molecule is removed creating a trans double bonds between carbons 2 and 3.
70
What is the sixth step of palmitic acid synthesis catalyzed by?
HD domain of FAS.
71
What is the seventh step of palmitic acid synthesis ?
Reduction: Finally, the double bond is reduced by the ER domain of FAS. NADPH is oxidized to NADP.
72
At the end of cycle-1 (involving 7 steps), FAS …
produces a 4C containing saturated butyric acid (Butyryl-ACP).
73
Cycle-2 is repeated beginning from____
Step2
74
What happens in step 2 of cycle 2?
Transfer of the 4C butyryl unit from the ACP to the Cys residue of KS domain
75
What happens in step 3 of cycle 2?
Attachment of Malonyl CoA to ACP domain
76
What happens in step 4 of cycle 2?
Condensation of butyryl and malonly releases CO2 | and yields a 6C containing fatty acid chain.
77
What happens in step 5 of cycle 2?
Reduction of carbonyl group (keto) at the third Carbon from the Sulfur group.
78
What happens in step 6 and 7 of cycle 2?
Dehydration and reduction
79
What happens at the end of cycle 2?
FAS adds 2 more carbons to the 4C butyryl and produces a | 6 carbon containing fatty acid chain, hexanoyl-ACP.
80
Cycles 3 to 7 (5 more cycles) will be repeated in the same pattern starting from the steps-.. In each cycle, FAS adds ..
2 to 7. 2C and elongates FA chain
81
Where are the 16C of palmitic acid obtained from?
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
Finally step of palmitic acid synthesis.
palmitoyl thioesterase (TE) of FAS cleaves the thioester bond and releases a saturated palmitate (16C) from the ACP domain using one H2O molecule.
83
Of the 7 cycles used in synthesizing a 16C palmitic acid Cycle 1: … Cycle 2:…
* 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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