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B2 Biochem > Fatty Acid Synthesis > Flashcards

Fatty Acid Synthesis Flashcards

1
Q

Source of FAs

A

Diet

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2
Q

What happens to excess dietary protein and carbs?

A

Converted to fatty acids and stored as TAG

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3
Q

What is De Novo synthesis?

A

Synthesis of FAs not from the diet.

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4
Q

Where does de novo FA synthesis occur?

Tissues

A

Liver, lactating mammary gland, adipose tissue

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5
Q

Where is De novo synthesis in the cell?

A

In the Cytosol.

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6
Q

What is the carbon source for growing fatty acid chains (in De Novo synthesis)?

A

Cytosolic acetyl CoA

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7
Q

What are the energy sources for De Novo Synthesis?

A

ATP and NADPH

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8
Q

What part of acetyl CoA is generated in the mitochondria?

A

The acetyl group

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9
Q

What part of acetyl CoA cannot pass through the inner mitochondrial membrane?

A

CoA

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10
Q

Why is Acetyl CoA required for FA production in the Cytosol?

A

The acetyl group is the carbon source. Must first be converted to citrate to be released into the Cytosol. the citrate is then converted back into Acetyl CoA once it’s into the Cytosol, by use of ATP andCoA.

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11
Q

What two molecules combine to make citrate?

A

OAA and Acetyl CoA (CoA is cleaved)

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12
Q

Steps of “Generating a pool of cytosolic Acetyl CoA”

A
  1. Mitochondrial Acetyl CoA is generated

2. Acetate exits mitochondria as citrate (to create cytosolic Acetyl CoA)

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13
Q

What can Acetyl CoA be generated from in the mitochondria?

A

Oxidation of pyruvate

B-oxidation of long carbon chain-CoA

Catabolism of ketone bodies and some AAs

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14
Q

How is citrate produced/cleaved in the mitochondria/Cytosol?

A

From OAA and Acetyl group.

Citrate accumulates to a high level in the mitochondria when Isocitrate-Dehydrogenase is inhibited by high ATP levels

Citrate exits mitochondria to the Cytosol

Citrate is cleaved by ATP-citrate lyase to produce cytosolic Acetyl CoA and OAA

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15
Q

FAs are likely to be generated during..

A

Well-fed state

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16
Q

Carboxylation of cytosolic Acetyl CoA forms..

A

Malonyl CoA

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17
Q

What does Acetyl CoA Carboxylase use to carboxylate Acetyl group of acetyl CoA?

A

CO2 and energy from ATP

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18
Q

What is so important about Acetyl CoA Carboxylase?

A

The Carboxylation/decarboxylation reaction provides energy for carbon to carbon condensations to elongate the growing Fatty Acid chain

This is the rate-limiting step and regulated step for FA synthesis.

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19
Q

What is the rate limiting step of FA synthesis? **

A

Carboxylation of cytosolic Acetyl CoA to form malonyl CoA

Via Acetyl CoA Carboxylase

Rate-limited because this is the step that provides the energy for the condensation of elongating and growing FA chains!

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20
Q

Short-term regulation of Acetyl CoA Carboxylase (ACC)

A

Inactive ACC dimers are activated by citrate

Activated ASS is deplymerized by end product (LCFAs) (inactivation)

AMPK inhibits ACC

Indirectly inhibited by Epinephrine and Glucagon

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21
Q

Long term regulation of ACC

A

High calorie, high carb diets increase ACC synthesis, therefore increasing FA synthesis

Low cal or high fat diet reduces FA synthesis by decreasing ACC synthesis

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22
Q

What inactivates/inhibits ACC?

A

LCFAs

AMPK

Epinephrine/glucagon

Low cal/high fat diet

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23
Q

What activates ACC?

A

Citrate

AMP/kinases

high cal/high carb diets

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24
Q

What is FAS?

A

FA Synthase, a multifunctional diametric enzyme in eukaryotes.

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25
Q

Each FAS has…

A

7 different enzymatic activities

A domain for covalent lay binding 4’-phosphopantetheine

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26
Q

The domain that covalently binds 4’-phosphopantetheine acts as:

A

An ACP (acyl carrier protein)

Carries acyl units on its thiol-group during FA synthesis

27
Q

Steps of FAS

A
  1. Acetate is transferred from Acetyl CoA to the ACP domain
  2. Acetate is transferred from ACP domain to cysteine residue (-SH) holding site on FAS
  3. 3-C malonate is transferred from malonyl CoA to ACP domain
  4. CO2 is released
  5. 3-ketoacyl group is reduced by NADPH to an alcohol
  6. Water molecule is removed and double bond is formed between C2 and C3 (alpha and beta)
  7. Double bond is reduced by NADPH

Result: 4-C compound, butyryl attached to FAS-ACP

28
Q

How does elongation of FA occur via FAS?

A

The Seven steps are repeated

29
Q

What initiates the elongation of FAs via FAS?

A

Transfer of butyryl to the cysteine residue holding site

30
Q

What is the rate limiting step of FAS?

A

Acetyl CoA Carboxylation to generate Malonyl CoA

31
Q

Each time the 7 steps are following, how many carbons are added to the growing chain?

A

2

32
Q

Final fatty acid length is:

Via FAS

A

16 carbons

Resulting in termination of synthesis with end-product palmitoyl-s-CoA

33
Q

What is palmitoyl-S-CoA?

A

The end product of FAS that is synthesized with then final FA length

34
Q

What does palmitoyl thioesterase do?

A

Cleaves the thioester bond releasing saturated palmitate (16:0)

35
Q

What is palmitate?

A

16:0 FA

36
Q

What does NADPH do in FA synthesis?

A

Functions as a biochemical reluctant, source of reducing agents for FA synthesis

37
Q

What is the predominant source of NADPH?

A

HMP shunt

38
Q

What is an additional source of NADPH?

A

Malate oxidation and decarboxylation by malic enzyme

NADPH is produced since NADP+ oxidized Malate to pyruvate

39
Q

Where is palmitate further elongated?

A

In the smooth endoplasmic reticulum

40
Q

How is palmitate further elongated?

A

In the SER, it uses 2-C units from malonyl CoA and reduction by NADPH

Requires specialized enzymes

41
Q

What tissue has special elongation capabilities and what does it produce?

A

The brain tissue.

Very LCFAs, more than 22 carbons

Required for brain lipids

42
Q

Where can fatty acid chains become desaturated?

A

In the SER

43
Q

The SER does what to LCFAs

A

Introduces Cis-double bonds, typically between C9 and C10.

44
Q

What is a common mono unsaturated FA?

A

18:1 (9)

45
Q

What is a less common mono unsaturated FA?

A

16: 1 (9)

46
Q

How are FAs stored?

A

As TAG (or MAG or DAG)

They lose their charge, forming neutral TAG

47
Q

What is the structure of TAG?

A

FAs esterified to glycerol

C1: saturated FA of varied length

C2: unsaturated FA of varied length

C3: saturated or unsaturated FA of varied length

48
Q

Is TAG soluble in water?

A

Yes, only

49
Q

What amphipathic molecule can TAGs form?

A

Micelles, independently

50
Q

TAG can coalesce and form…

A

Nearly anhydrous, cytosolic oil droplets

51
Q

TAG molecule is formed from:

A

Glycerol phosphate and fatty acyl CoA

52
Q

What is glycerol phosphate?

A

The initial acceptor of activated FAs during TAG synthesis

53
Q

Free FAs must be converted back to ___________ for TAG formation

A

Their activated form, acyl CoA

54
Q

How can glycerol phosphate be synthesized?

A

In the liver and in adipose tissue.

Produced from glucose

55
Q

How is glycerol phosphate produced?

A

Glucose -> DHAP -> glycerol phosphate

In liver or adipose tissue

56
Q

What is a way for glycerol phosphate to be produced specific to only the liver?

A

Glycerol kinase converts free glycerol to glycerol phosphate

57
Q

GLUT-4 activity is ________ dependent. Which means what?

A

Insulin dependent. When there are low levels of insulin, or glucose, adipose tissue cannot synthesize glycerol phosphate.

Therefore no TAGs are produced.

58
Q

What catalyze a free FAs to Acetyl CoA?

A

Fatty acyl CoA synthase (thiokinase)

59
Q

What reactions are required for synthesis of TAG molecule?

A
  1. Sequential addition of 2 FAs from fatty acyl CoA to glycerol phosphate
  2. Removal of phosphate group
  3. Addition of 3rd FA

Via acyltransferase, phophatase, and acyltransferase, respectively

60
Q

What is the fate of TAG in adipose tissue?

A

Stored. As cytosolic lipid droplets.

Easily mobilized in this format, when fuel is required.

61
Q

What is the fate of TAG in the liver?

A

Stored (in small amounts)

Packaged as VLDL (very low density lipoproteins)

62
Q

VLDLs function to:

A

Be secreted to the blood and deliver lipids to peripheral tissues

63
Q

What do chylomicrons do?

A

Deliver dietary acquired lipids

64
Q

What do VLDLS deliver?

A

De novo synthesized lipids.

B2 Biochem (13 decks)

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