Fatty Acid Synthesis Flashcards

1
Q

What is the primary source of Fatty acids?

A

Diet

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2
Q

What happends to excess dietary protein and carbs?

A

converted to fatty acids for storage as TAG

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3
Q

De Novo Synthesis: in adults, most FA synthesis is in the ____ and _______, some in adipose

A

liver and lactating mammary glands

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4
Q

De Novo Synthesis:

______ is the carbon source for growing fatty acid chains

A

cytosolic acetyl CoA

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5
Q

De Novo Synthesis of FA occurs in the _____

A

cytosol

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6
Q

Energy source for De Novo Synthesis?

A

ATP and NADPH

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7
Q

Major Requirements/Considerations for Generating a pool of cytosolic acetyl CoA:
The acetyl-group of acetyl CoA is:
A).
B).

A

A. generated in the mitochondria

B. required for fatty acid production in the cytosol

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8
Q

The ____ portion of acteyl CoA cannot cross the inner mitochondrial membrane

A

CoA

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9
Q

Production of cytosolic acetyl CoA requires a process for generation and delivery of the ______ of mitochondria acetyl CoA to the cytosol

A

acetyl group

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10
Q

Generating a pool of cytosolic acetyl CoA
Step 1:
Mitochondrial acetyl CoA is generated from
A.
B.
C.

A

A. oxidation of pyruvate
B. Beta oxidation of long carbon chain-CoA
C. catabolism of ketone bodies and some amino acids

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11
Q

Describe Step 2.

A

Acetate exits mitochondria and enters cytosol as citrate

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12
Q

The accumulation of citrate in the mitochondria requires that high levels of ATP inhibit _______

A

isocitrate-dehydrogenase.

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13
Q

Fatty acids are likely to be generated only in the ______

A

well-fed state

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14
Q

In the Carboxylation of cytosolic acetyl CoA to form malonyl CoA, _______ uses CO2 and energy from ATP hydrolysis to carboxylate the acetyl group of Acetyl CoA.

A

Acetyl CoA Carboxylase

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15
Q

What is the importance of the Carboxylation of Cytosolic Acetyl CoA to form Malonyl CoA?

A
  • the carboxylation (and subsequent decarboxylation) rxns PROVIDE ENERGY for C-to-C condensations to elongate the growing FA chain
  • carboxylation of acetyl CoA is the RATE-LIMITING and REGUALTED STEP for FA synthesis
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16
Q

Short-term regulation of Acetyl CoA Carboxylase

-inactive ACC allosterically activated to polymerized form by _______

A

Citrate

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17
Q

ACC is indirectly inhibited by ____ and _____

A

epinephrine and glucagon

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18
Q

Short-term regulation of Acetyl CoA Carboxylase

-activated ACC depolymerized by the end product _____

A

Long-Chain Fatty Acyl CoA

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19
Q

Short-term regulation of Acetyl CoA Carboxylase

____ reversibly phosphorylates and inhibits ACC

A

AMPK

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20
Q

Short Term Regulation of Acetyl CoA Carboxylase

_____ is allosterically activated by AMP and by phosphorylation (by kinases), one of which is cAMP dependent PKA

A

AMPK

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21
Q

Long Term Regulation of ACC:

_____ increase ACC synthesis –> increase FA synthesis

A

prolonged high calorie, high carb diet

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22
Q

Long Term Regulation of ACC:

____ reduces fatty acid synthesis by decreasing ACC synthesis

A

low calorie/high-fat diet

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23
Q

______ is a multifunctional dimeric enzyme in eukaryotes

A

Fatty Acid Synthase (FAS)

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24
Q

Describe a FAS monomer:

A

contains 7 different enzymatic activities and a domain for covalently binding 4’-phosphopantetheine

25
Q

4’-phosphopantetheine functions as an

A

acyl carrier protein (ACP)

26
Q

ACP carries acyl units on its ________ during FA synthesis

A

terminal thiol group (-SH)

27
Q

Describe Step 1 of the FAS catalyzed reactions.

A

Acetate is transferred from acetyl CoA to ACP domain

28
Q

Describe Step 2 of the FAS catalyzed reactions.

A

Acetate (2-C fragment) is transferred from ACP –> cysteine holding site on FAS

29
Q

Describe Step 3 of the FAS catalyzed reactions.

A

3 carbon malonate is trasnferred from malonyl CoA to ACP domain

30
Q

Describe Step 4 of the FAS catalyzed reactions.

A

CO2 previously added by acetyl CoA carboxylase is released

31
Q

In Step 4 of FAS catalyzed reactions, what remains attached to the ACP?

A

A 4-Carbon Product

32
Q

What is significant about Step 4 of FAS catalyzed reactions?

A

Energy from decarboxylation drives a condensation reaction between the acyl group at the holding site cysteine and the malonyl grp on ACP domain

33
Q

What is the product of Step 4 of FAS catalyzed reactions?

A

3-ketoacyl group which is converted to a saturated acyl group by two reduction reactions using NADPH and a dehydration reaction

34
Q

Describe Step 5 of the FAS catalyzed reactions.

A

The 3-ketoacyl group is reduced by NADPH to an alcohol

35
Q

Describe Step 6 of the FAS catalyzed reactions.

A

A water molecule is removed and double bond formed b/w C-2 and C-3

36
Q

Describe Step 7 of the FAS catalyzed reactions.

A

Double bond is reduced by NADPH

37
Q

What is the result of Step 7 of the FAS catalyzed reactions?

A

4-C compound (butyryl) with three terminal carbons saturated and attached to FAS-ACP

38
Q

continued chain elongation requires repeating the 7 steps. The steps are followed 7 times, each round adding _____ to the growing chain.

A

2-C

39
Q

initiation of elongation requires transfer of the _____ to the cysteine residue holding site of FAS

A

butyryl

40
Q

Final Fatty Acid length is _____. Resulting in termination with end product _____

A

16-C; palmitoyl-S-CoA

41
Q

______ cleaves the thiester bond releasing saturated palmitate (16:0)

A

palmitoyl thioesterase

42
Q

_____functions as a biochemical reductant

A

NADPH

43
Q

Name the two sources of NADPH

A

HexoseMonoPhosphate (HMP) Shunt (predominant source)

Malate Oxidation and decarboxylating by malic enzyme (AKA NADP+ dependent malate dehydrogenase)

44
Q

From each HMP comitted Glucose 6-Phosphate, two _____ are produced

A

NADPH

45
Q

Brain tissue has special elongation capabilities to generate _______ that are required for brain lipids

A

very long chain fatty acids

46
Q

The ______ contains desaturases that are responsible for the desaturation of LCFAs

A

smooth ER

47
Q

The desaturases introduce _____, typically between carbons 9 and 10.

A

cis- double bonds

48
Q

_____ is a common mono unsaturated fatty acid, while ____ is less common.

A. 16:1(9)
B. 16:0
C. 18:1(9)

A

18: 1(9)
16: 1(9)

49
Q

esterified FA become ____ TAG molecules

A

neutral

50
Q

_____ is:

a) only slightly soluble in water
b) unable to form micelles independently
c) able to coalesce and form nearly anhydrous, cytosolic oil droplets

A

TAG

51
Q

Synthesis of TAG requires the production of TAG building blocks:
_____ and ________

A

glycerol phosphate and acyl CoA

52
Q

_____ is the initial acceptor of activated FA during TAG synthesis

A

Glycerol Phosphate

53
Q

What are the two pathways to produce glycerol phosphate?

A

a) in the liver and adipose tissue: produced from glucose via glycolytic pathway
b) in liver only: glycerol kinase converts free glycerol–> glycerol phosphate

54
Q

Free Fatty acid conversion to acetyl CoA is catalyzed by __________

A

fatty acyl CoA synthase (thiokinase)

55
Q

Name the reactions required to assemble TAG from glycerol phosphate and fatty acyl CoA pool
1)
2)
3)

A

1) addition of two FA from fatty acyl CoA –> glycerol phosphate by acyltransferase
2) removal of the phosphate group by phosphatase
3) addition of the third fatty acid by acyltransferase

56
Q

In ______;

a) TAG is stored as cytosolic lipid droplets
b) TAG in this format is easily mobilized when fuel is required

A

Adipose Tissue

57
Q

In ______:

a) small amounts of TAG are stored
b) TAG generated here is packaged w/other lipids and apoproteins —> VLDL
c) Nascent VLDL are secreted to the blood and deliver do novo synthesized lipids to peripheral tissues

A

Liver

58
Q

deliver exogenous dietary acquired lipids

A

chylomicrons

59
Q

____ deliver de novo synthesized lipids

A

VLDL