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Y Biochemistry 2 > Midterm II: Fatty Acid Synthesis (Ben) > Flashcards

Midterm II: Fatty Acid Synthesis (Ben) Flashcards

1
Q

In what 3 tissues does fatty acid synthesis occur?

And in what part of the cell?

A
  • Liver
  • Adipose Tissue
  • Lactating Mammary Gland
  • in the cytosol
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2
Q

What enzyme produces fatty acids?

What is special about its structure and function?

A

Fatty Acid Synthase

  • one single polypeptide chain with 7 different active sites for different reactions in separate domains
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3
Q

What is the “committed step” in fatty acid synthesis?

Reactants?

Enzyme + co-factor?

Products?

A

The first step… carboxylation…

Reactants: Acetyl-CoA + HCO3- + ATP

Enzyme: Acetyl-CoA Carboxylase + Biotin

Products: Malonyl-CoA

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4
Q

How is biotin connected to acetyl-CoA carboxylase?

A
  • covalently bound to a lysine side chain of the enzymes “biotin carrier protein”
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5
Q

Acetyl-CoA Carboxylase is a “multienzyme protein” and performs a 2-step reaction.

What is the first step?

A

Biotin Carboxylase transfers a carboxyl group from bicarbonate to biotin in the presence of ATP.

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6
Q

Acetyl-CoA Carboxylase is a “multienzyme protein” and performs a 2-step reaction.

What is the second step?

A

Carboxyl transferase transfers the carboxyl group from biotin to acetyl-CoA, forming malonyl-CoA

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7
Q

How are biotin + its attached carboxyl group moved between the two enzymes within Acetyl-CoA carboxylase?

A

via biotin carrier protein

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8
Q

What is the protein responsible for fatty acid synthesis?

How many enzymatic actions does it have?

A

Fatty Acid Synthase

  • has 6 enzymes and an acyl carrier protein
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9
Q

What first happens to fatty acid synthase before it can begin building a fatty acid chain?

A

Acetyl group of acetyl-CoA is transferred from…

ACP-SH to…

Cys-SH of …

β-ketoacyl-ACP synthase​ part of FA synthase, via…

MAT

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10
Q

On what special part of acyl carrier protein do molecules bind to become involved in fatty acid synthesis?

A

the -SH group on the vitamin panthothenic acid

(in 4’-phosphopantetheine form)

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11
Q

On which enzyme in the fatty acid synthase complex is the Cys-SH which binds acetyl-CoA found?

A

β-ketoacyl-ACP synthase

or “KS” part

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12
Q

What happens in fatty acid synthesis after acetyl-CoA binds to Cys-SH?

A

a Malonyl group is transferred to the ACP-SH by MAT

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13
Q

Once both the malonyl and acetyl groups are connected to fatty acid synthase…

What is the first step of fatty acid synthesis?

Reactants?

Enzyme?

Products?

A

Condensation…

Reactants: Acetyl + Malonyl groups

Enzyme: β-ketoacyl-ACP Synthase

Product: Acetoacetyl-ACP + CO2

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14
Q

After condensation of the malonyl + acetyl groups…

what is the 2nd step in fatty acid synthesis?

Reactants?

Enzyme?

Products?

A

Reduction of carbonyl group…

Reactants: Acetoacetyl-ACP + NADPH + H+

Enzyme: β-Ketoacyl-ACP Reductase (KR)

Products: β-Hydroxybutyryl-ACP + NADP+

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15
Q

After reduction of the carbonyl group at C-3…

what is the 3rd step of fatty acid synthesis?

Reactants?

Enzyme?

Product?

A

Dehydration to form a double bond…

Reactants: β-Hydroxybutyryl-ACP

Enzyme: β-Hydroxybutyryl-ACP Dehydratase (DH)

Product: trans-Δ2-Butenoyl-ACP + H20

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16
Q

After dehydration to form a double bond…

what is the 4th step in fatty acid synthesis?

Reactant?

Enzyme?

Product?

A

Reduction of the double bond…

Reactant: trans-Δ2-Butenoyl-ACP + NADPH + H+

Enzyme: Enoyl-ACP-Reductase

Product: Butyryl-ACP + NADP+

17
Q

After reduction of a double bond…

what is the 5th and final step of fatty acid synthesis before the cycle begins again?

A

Translocaton of Butyryl-ACP to the Cys-SH of β-Ketoacyl-ACP Synthase (KS)

18
Q

After the formation of a butyryl group, how does each subsequent round of the fatty acid synthase cycle begin?

A

ACP is recharged with another malonyl group by MAT

19
Q

How many fatty acid synthase cycles does it take to produce palmitate?

And how is it finally released from the enzyme?

A

After 7 cycles a 16C palmitate is produced…

…and released by thioesterase enzyme

20
Q

What is the overall reaction for the seven cycles of fatty acid synthase activity leading to production of one palmitate?

(Including the synthesis of the Malonyl-CoA substrates.)

A
21
Q

What condition in lipid synthesizing tissues makes them favorable environments for this process?

A

High [NADPH]/[NADP+] ratio

(in the cytosol of adipose + liver cells)

22
Q

Where does most of the NADPH used in FA synthesis come from?

A

Pentose Phosphate Pathway

and some from Malic Enzyme

23
Q

How does acetyl-CoA get from the mitochondria to the cytosol for FA synthesis?

A

it is transported out of the mitochondria as citrate after combining with oxaloacetate via citrate synthase

24
Q

What happens to citrate after it has left the mitochondria for FA synthesis?

Enzyme + co-factors?

Product?

A

it is converted back to acetyl-CoA via citrate lyase

  • this requires ATP and yields oxaloacetate, ADP + Pi
25
Q

After oxaloacetate is released from citrate in the cytosol, what happens to it?

A

It is converted back into malate via malate dehydrogenase using NADH + H+

26
Q

What 2 things can happen with malate that has been formed from oxaloacetate in the cytosol?

And what byproduct of one of these things contributes directly to fatty acid synthesis?

A
  1. re-enters the mitochondria directly
  2. conversion to pyruvate via malic enzyme + NADP+
    • ​yields NADPH for FA synthase
27
Q

What are 3 regulatory mechanisms of acetyl-CoA Carboxylase?

A
  1. Negative feedback inhibition - via palmitate
  2. Allosteric Stimulation - via citrate
  3. Covalent Modification - insulin —> dephosphorylation —> activation
28
Q

Increased levels of what two citric acid cycle molecules inhibit a key citric acid cycle enzyme?

(which then leads to increased FA synthesis)

A

Increased acetyl-CoA and ATP inhibit isocitrate dehydrogenase

  • this leads to increased citrate + FA synthesis
29
Q

What is the mechanism for glucagon’s effect on fatty acid synthesis?

A
  • Gs
  • Adenylyl Cyclase
  • [cAMP] increase
  • PKA
  • Phosphorylation/deactivation of ACC
30
Q

How does the presence of Palmitoyl-CoA affect FA synthesis?

(Generally and via what mechanisms?)

A

It inhibits it, via…

  • Ac-CoA Carboxylase inhibition
  • Inhibition of citrate movement to cytosol
  • G-6-P Dehydrogenase inhibition
    • key pentose phosphate pathway enzyme
    • leads to decreased [NADPH]

Y Biochemistry 2 (24 decks)

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