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
WHat does Fatty Acid Synthase do to MALONYL COA?
takes 2C FROM MALONYL COA, GIVES IT TO GROWING FATTY ACYL CHAIN
26
each subunit of Fatty Acid Synthase contains (2)
1. **7 catalytic activities** 2. **an acyl carrier protein** in a single polypeptide chain
27
**_Phosphopantetheine_** is linked to a **serine** within the \_\_\_\_) portion of **fatty acid synthase**
acyl carrier protein (ACP)
28
\_\_\_ of **_fatty aci synthase_** reacts with **malonyl COA t**o form a **thioester fond**
sulfhydral group
29
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.
head-to-tail s
30
what is fatty acid synthase derived from?
pantothemnic acid?
31
condensation step **Malonyl CoA** attaches to the ____ part of the ACP of **FAS**
phosphopantetheinyl (P)
32
step 2: condensation after** acetyl group from acetyl Coa** first associates with the ACP phospho-pantetheinyl sulfhydryl group, it is then
transferred to the **cysteine sulfhydryl** of the other subunit.
33
after acetyl group from acetyl coa associated with ACP sulfhydryl group. what happens?
**Malonyl** from malonyl CoA then associates with the **ACP phospho-pantetheinyl sulfhydryl group.**
34
**step 2: condensation** The acetyl and malonyl groups condense with release of the malonyl carboxyl group as
CO2
35
step 2: condensation ## Footnote after coa2 is released by condensation, ___ is created
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
step 3: n Fatty Acid Synthesis include a reduction of the β−keto group to an\_\_\_
alcohol
37
step 4 dehydration to form a \_\_\_\_
double bond
38
step 5 another reduction step reduces the\_\_\_\_\_
double bond.
39
in fa synthesis, NADPH provides the reducing equivalents for what steps
step 3 -- reduing b-keto group --\> alcohol step 5 -- reducing double bound
40
steps 2-5 are repeated with the result being a \_\_\_
6C fatty acyl chain
41
after stepes 2-5 make 6C fatty acyl chain, the series of reactions is repeated until
he fatty acid chain is 16 carbons
42
after the he fatty acid chain is 16 carbons then
hydrolysis occurs and palmitate is released.
43
after palmitiate si reelased from fAS it is activated to
palmitoyl coa
44
palmityl coa and other long chain fatty acyl coas can be elongated ___ carbons at a time
two
45
where are fa chains elongated? by what enzymes?
in the er by elongases
46
difference between steps in elongation and synrhsis of fa?
the long fatty acid is attached to **coenzyme A** instead of a phophopanthetinyl residue
47
**Desaturation** is the **_oxidation of fatty acids_** resulting in
cis double bonds.
48
\_\_\_\_ of FA creates lipids of **increasing structural and functional complexity** with distinct biological roles.
Desaturation
49
what does fa desaturation require? where is it found
desaturases, found in the er
50
what do desaturases require
o2 nadh cytochrome b5 (where electrons pass through)
51
During starvation, **desaturase** activities
decrease sharply
52
desaturase ___ upon feeding with carbohydrate.
increases
53
When large amounts of ____ are eaten **desaturase** activities decrease.
unsaturated fats
54
Humans have what three distinct **Desaturases** distinguished by the **position of the double bond insertion** within the fatty acid chain.
Ø Δ9 desaturase Ø Δ6 desaturase Ø Δ5 desaturase
55
The most common desaturation reactions involve an oxidation leading to a double bond between \_\_\_
C9 and C10.
56
what is required for eicosinoid synthesis.
**polyunusaturated FAs** with double bonds 3 C s(ω3) o r6 carbons (ω6) from the methyl end
57
We do not synthesize the\_\_\_\_ fatty acids de novo so they must come from our diet
ω3 and ω6
58
linoleic and linolenic fatty acids primarily from plant oils help prodvide
ω3 and ω6 fatty acids, since we do not syntehsis these de novo
59
importance of **arachidonic acid?**
- PRECURSOR OF SEVERAL EICOSANOIDS - IMPORTANT COMPONENT OF MEMBRANE LIPIDS
60
**_Linoleic acid_** can be converted by **elongation and desaturation** reactions to \_\_\_
arachidonic acid
61
is Arachidonic acid an essential fa?
not if lioleic acid is present since that can syntehsize it
62
\_\_\_\_ is a susbtrate for leukotrienes, thromboxanes, prostaglandins
arachidonic acid
63
Eicosanoids include the (3)
prostaglandins, thromboxanes and leukotrienes
64
Eicosanoids tend to be unstable and ahve very __ biological half life
short
65
what are the three pathways that **metabolize** **_arachidonic acid_**
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
the cyclic (or cyclooxygenase) pathway of eicosanoids syntheis forms the (3)
prostaglandins, thromboxanes and prostacyclins;
67
the linear (or lipoxygenase) pathway of eicosanoid synthesis forms
--\> HPETE ----\> leukotrienes, lipoxins, HETEs
68
the cytochrome P450 pathway of eicosanoid synthesis forms \_\_\_.
epoxides
69
(aspirin and other NSAIDs act on \_\_\_\_
cyclooxygenase (which converts converts arachidonic acid to PGH2)
70
**cyclooxygenase** converts __ to \_\_\_
arachidonic acid to PGH2
71
cyclooxygenase\_\_\_ is tjhe form expressed in all tisues
cox-1
72
cyclooxygenase\_\_\_ is tjhe form regulated by cytokines and growth factors. it is inc in inflamattion
cox-2
73
\_\_\_ is an irreversible inhbiitor of cox-1 and cox-2
aspirin
74
\_\_\_ is an reverisible inhbiitor of cox-1 and cox-2
acetaminophen and ibuprofen