Fatty Acid Synthesis Flashcards

1
Q

Fatty acids are synthesized primarily in the ___

A

liver.

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2
Q

how to get FA from pyrvuate?

A
  1. pyvuvate –> citrate
  2. citrate leaves mitocondira

3. citrate —> acetyl CoA

  1. acetyl CoA –> malonyl CoA
  2. manlonyl CoA is 2C donot for FA synthesis
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3
Q

____ is 2C donot for FA synthesis

A

manlonyl CoA

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4
Q

what is the product of FA synthesis? what is its structure?

A

palmitic acid, a sixteen carbon saturated fatty acid.

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5
Q

pyruvate –> Pyruvate dehydrogenase by??

A

Pyruvate dehydrogenase

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6
Q

pyruvate –> oxaloacetate (OAA) by??

A

Pyruvate carboxylase

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7
Q

** Pyruvate carboxylase** and Pyruvate dehydrogenase are regulated based on what?

A

e level of acetyl CoA in the mitochondria

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8
Q

When Acetyl CoA is at high concentration the Pyruvate dehydrogenase is ____

A

inhibited

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9
Q

When Acetyl CoA is at high concentration the Pyruvate dehydrogenase is inhibited causing —->

A

an INC Pyruvate carboxylasse —->INC OAA.

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10
Q

The reduction in acetyl CoA leads to

A
  1. activation of the dehydrogenase
  2. inhibition of carboxylase.
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11
Q

What happens with Citrate in the cytosol

A

cleaved to Acetyl CoA and OAA by _Citrate Lyase. _

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12
Q

in the cytosol, citrate is cleaved to Acetyl CoA and OAA by ___

A

Citrate Lyase.

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13
Q

Whybreak down citrate in the cytosol too when you have already produced Acetyl CoA and OAA in the mitochondria?

A
  • The Pyruvate dehydrogenase is only found in the mitochondria.
  • Acetyl CoA cannot cross the mitochondrial double membrane.
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14
Q

NADPH is required for the ___ of Fatty Acids.

A

NADPH

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15
Q

NADPH is required for the synthesis of Fatty Acids.

One source of NADPH for synthesis of FA is the recycling of the OAA

what are the two steps?

A
  1. OAA is reudced to Malate by NADH dependent maltase dehydrogenase
  2. Malate converted to NADP-dependend Malix enzyme
  3. Malic enzyme oxidizes and decboxyltes Malate –> pyruvate
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16
Q

sources of NADPH for FA synthesis (2)

A
  1. recycling OAA
  2. Pentose Phosphate pathway
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17
Q

2 enzymes involved in FA synthesis?

A

Acetyl CoA Carboxylase and Fatty Acid Synthase

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18
Q

___ enzymes is involved in the rate controlling step of FA synthesis

A

Acetyl CoA Carboxylase

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19
Q

what rxn does Acetyl CoA Carboxylase catlayze in Fa synthesis?

A

Acetyl CoA —> Malonyl COA

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20
Q

Acetyl CoA —> Malonyl COA

what is the cofactor ACC binds to?

A

biotin

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21
Q

Acetyl CoA —> Malonyl COA

waht is consumed? generated?

A

ATP hydrolysized to ADP + Phosphate

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22
Q

What regulates Acetyl CoA Carboxylase?

A
  1. Citrate – causes it to polymerize
  2. Insulin stim. phopshatase
  3. Caloric intake/ACC transcription levels
  4. ** Glucagon/Epinephrine stimulated A-Kinase**
  5. ** Palmitoyl CoA** levels
  6. ** AMP** (low energy levels)
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23
Q

5 steps in FA synthesis?

A
  1. Activation: carboxylation of acetyl CoA to malonyl CoA
  2. Condensation: formation of the β -keto group
  3. Reduction of the β -keto group
  4. Dehydration of the a, b carbons
  5. Reduction of the a, b double bond
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24
Q

what are steps 2-5 of FA synthesis catalyzed by?

A

Fatty Acid Synthase (FAS)

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25
Q

WHat does Fatty Acid Synthase do to MALONYL COA?

A

takes 2C FROM MALONYL COA, GIVES IT TO GROWING FATTY ACYL CHAIN

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26
Q

each subunit of Fatty Acid Synthase contains (2)

A
  1. 7 catalytic activities
  2. an acyl carrier protein in a single polypeptide chain
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27
Q

Phosphopantetheine is linked to a serine within the ____) portion of fatty acid synthase

A

acyl carrier protein (ACP)

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28
Q

___ of fatty aci synthase reacts with malonyl COA to form a thioester fond

A

sulfhydral group

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29
Q

fatty acid synthase

the two subunits associate ____o that the phospho-pantetheinyl sulfhydryl group on one subunit is close to the cysteinyl sulfhydryl group on the other subunit.

A

head-to-tail s

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30
Q

what is fatty acid synthase derived from?

A

pantothemnic acid?

31
Q

condensation step

Malonyl CoA attaches to the ____ part of the ACP of FAS

A

phosphopantetheinyl (P)

32
Q

step 2: condensation

after** acetyl group from acetyl Coa** first associates with the ACP phospho-pantetheinyl sulfhydryl group, it is then

A

transferred to the cysteine sulfhydryl of the other subunit.

33
Q

after acetyl group from acetyl coa associated with ACP sulfhydryl group. what happens?

A

Malonyl from malonyl CoA then associates with the ACP phospho-pantetheinyl sulfhydryl group.

34
Q

step 2: condensation

The acetyl and malonyl groups condense with release of the malonyl carboxyl group as

A

CO2

35
Q

step 2: condensation

after coa2 is released by condensation, ___ is created

A

4C ** β−keto acyl chain** which is attached to the ACP phospho-pantetheinyl sulfhydryl group.

* will eventually become the omega methyl group of palmitate is labelled ω.

36
Q

step 3:

n Fatty Acid Synthesis include a reduction of the β−keto group to an___

A

alcohol

37
Q

step 4

dehydration to form a ____

A

double bond

38
Q

step 5

another reduction step reduces the_____

A

double bond.

39
Q

in fa synthesis, NADPH provides the reducing equivalents for what steps

A

step 3 – reduing b-keto group –> alcohol

step 5 – reducing double bound

40
Q

steps 2-5 are repeated with the result being a ___

A

6C fatty acyl chain

41
Q

after stepes 2-5 make 6C fatty acyl chain, the series of reactions is repeated until

A

he fatty acid chain is 16 carbons

42
Q

after the he fatty acid chain is 16 carbons then

A

hydrolysis occurs and palmitate is released.

43
Q

after palmitiate si reelased from fAS it is activated to

A

palmitoyl coa

44
Q

palmityl coa and other long chain fatty acyl coas can be elongated ___ carbons at a time

A

two

45
Q

where are fa chains elongated? by what enzymes?

A

in the er

by elongases

46
Q

difference between steps in elongation and synrhsis of fa?

A

the long fatty acid is attached to coenzyme A instead of a phophopanthetinyl residue

47
Q

Desaturation is the oxidation of fatty acids resulting in

A

cis double bonds.

48
Q

____ of FA creates lipids of increasing structural and functional complexity with
distinct biological roles.

A

Desaturation

49
Q

what does fa desaturation require? where is it found

A

desaturases, found in the er

50
Q

what do desaturases require

A

o2

nadh

cytochrome b5 (where electrons pass through)

51
Q

During starvation, desaturase activities

A

decrease sharply

52
Q

desaturase ___ upon feeding with carbohydrate.

A

increases

53
Q

When large amounts of ____ are eaten desaturase activities decrease.

A

unsaturated fats

54
Q

Humans have what three distinct Desaturases distinguished by the position of the double bond insertion within the fatty acid chain.

A

Ø Δ9 desaturase
Ø Δ6 desaturase
Ø Δ5 desaturase

55
Q

The most common desaturation reactions involve an
oxidation leading to a double bond between ___

A

C9 and C10.

56
Q

what is required for eicosinoid synthesis.

A

polyunusaturated FAs with double bonds 3 C s(ω3) o r6 carbons (ω6) from the methyl end

57
Q

We do not synthesize the____ fatty acids de novo so they must come from our diet

A

ω3 and ω6

58
Q

linoleic and linolenic fatty acids primarily from plant oils help prodvide

A

ω3 and ω6 fatty acids, since we do not syntehsis these de novo

59
Q

importance of arachidonic acid?

A
  • PRECURSOR OF SEVERAL EICOSANOIDS
  • IMPORTANT COMPONENT OF MEMBRANE LIPIDS
60
Q

Linoleic acid can be converted by elongation and desaturation reactions to ___

A

arachidonic acid

61
Q

is Arachidonic acid an essential fa?

A

not if lioleic acid is present since that can syntehsize it

62
Q

____ is a susbtrate for leukotrienes, thromboxanes, prostaglandins

A

arachidonic acid

63
Q

Eicosanoids include the (3)

A

prostaglandins, thromboxanes and leukotrienes

64
Q

Eicosanoids tend to be unstable and ahve very __ biological half life

A

short

65
Q

what are the three pathways that metabolize arachidonic acid

A
  1. via cycloxgenase – forms the prostaglandins, thromboxanes and prostacyclins;
  2. via lipoxygenase – forms leukotrienes, hydroxyeicosatetraenoic acids (HETEs), and lipoxins
  3. via cytochrome p50 – forms epoxides.
66
Q

the cyclic (or cyclooxygenase) pathway of eicosanoids syntheis forms the (3)

A

prostaglandins,
thromboxanes and prostacyclins;

67
Q

the linear (or lipoxygenase) pathway of eicosanoid synthesis forms

A

–> HPETE —-> leukotrienes, lipoxins, HETEs

68
Q

the cytochrome P450 pathway of eicosanoid synthesis forms ___.

A

epoxides

69
Q

(aspirin and other NSAIDs act on ____

A

cyclooxygenase (which converts converts arachidonic acid to PGH2)

70
Q

cyclooxygenase converts __ to ___

A

arachidonic acid to PGH2

71
Q

cyclooxygenase___ is tjhe form expressed in all tisues

A

cox-1

72
Q

cyclooxygenase___ is tjhe form regulated by cytokines and growth factors.

it is inc in inflamattion

A

cox-2

73
Q

___ is an irreversible inhbiitor of cox-1 and cox-2

A

aspirin

74
Q

___ is an reverisible inhbiitor of cox-1 and cox-2

A

acetaminophen and ibuprofen