Fatty Acid Synthesis

Question 1

What is the primary source of Fatty acids?

Answer 1

Diet

Question 2

What happends to excess dietary protein and carbs?

Answer 2

converted to fatty acids for storage as TAG

Question 3

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

Answer 3

liver and lactating mammary glands

Question 4

De Novo Synthesis:

______ is the carbon source for growing fatty acid chains

Answer 4

cytosolic acetyl CoA

Question 5

De Novo Synthesis of FA occurs in the _____

Answer 5

cytosol

Question 6

Energy source for De Novo Synthesis?

Answer 6

ATP and NADPH

Question 7

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

Answer 7

A. generated in the mitochondria

B. required for fatty acid production in the cytosol

Question 8

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

Answer 8

CoA

Question 9

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

Answer 9

acetyl group

Question 10

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

Answer 10

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

Question 11

Describe Step 2.

Answer 11

Acetate exits mitochondria and enters cytosol as citrate

Question 12

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

Answer 12

isocitrate-dehydrogenase.

Question 13

Fatty acids are likely to be generated only in the ______

Answer 13

well-fed state

Question 14

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.

Answer 14

Acetyl CoA Carboxylase

Question 15

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

Answer 15

• 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

Question 16

Short-term regulation of Acetyl CoA Carboxylase

-inactive ACC allosterically activated to polymerized form by _______

Answer 16

Citrate

Question 17

ACC is indirectly inhibited by ____ and _____

Answer 17

epinephrine and glucagon

Question 18

Short-term regulation of Acetyl CoA Carboxylase

-activated ACC depolymerized by the end product _____

Answer 18

Long-Chain Fatty Acyl CoA

Question 19

Short-term regulation of Acetyl CoA Carboxylase

____ reversibly phosphorylates and inhibits ACC

Answer 19

AMPK

Question 20

Short Term Regulation of Acetyl CoA Carboxylase

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

Answer 20

AMPK

Question 21

Long Term Regulation of ACC:

_____ increase ACC synthesis –> increase FA synthesis

Answer 21

prolonged high calorie, high carb diet

Question 22

Long Term Regulation of ACC:

____ reduces fatty acid synthesis by decreasing ACC synthesis

Answer 22

low calorie/high-fat diet

Question 23

______ is a multifunctional dimeric enzyme in eukaryotes

Answer 23

Fatty Acid Synthase (FAS)

Question 24

Describe a FAS monomer:

Answer 24

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

Question 25

4'-phosphopantetheine functions as an

Answer 25

acyl carrier protein (ACP)

Question 26

ACP carries acyl units on its ________ during FA synthesis

Answer 26

terminal thiol group (-SH)

Question 27

Describe Step 1 of the FAS catalyzed reactions.

Answer 27

Acetate is transferred from acetyl CoA to ACP domain

Question 28

Describe Step 2 of the FAS catalyzed reactions.

Answer 28

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

Question 29

Describe Step 3 of the FAS catalyzed reactions.

Answer 29

3 carbon malonate is trasnferred from malonyl CoA to ACP domain

Question 30

Describe Step 4 of the FAS catalyzed reactions.

Answer 30

CO2 previously added by acetyl CoA carboxylase is released

Question 31

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

Answer 31

A 4-Carbon Product

Question 32

What is significant about Step 4 of FAS catalyzed reactions?

Answer 32

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

Question 33

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

Answer 33

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

Question 34

Describe Step 5 of the FAS catalyzed reactions.

Answer 34

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

Question 35

Describe Step 6 of the FAS catalyzed reactions.

Answer 35

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

Question 36

Describe Step 7 of the FAS catalyzed reactions.

Answer 36

Double bond is reduced by NADPH

Question 37

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

Answer 37

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

Question 38

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

Answer 38

2-C

Question 39

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

Answer 39

butyryl

Question 40

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

Answer 40

16-C; palmitoyl-S-CoA

Question 41

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

Answer 41

palmitoyl thioesterase

Question 42

_____functions as a biochemical reductant

Answer 42

NADPH

Question 43

Name the two sources of NADPH

Answer 43

HexoseMonoPhosphate (HMP) Shunt (predominant source) | Malate Oxidation and decarboxylating by malic enzyme (AKA NADP+ dependent malate dehydrogenase)

Question 44

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

Answer 44

NADPH

Question 45

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

Answer 45

very long chain fatty acids

Question 46

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

Answer 46

smooth ER

Question 47

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

Answer 47

cis- double bonds

Question 48

_____ is a common mono unsaturated fatty acid, while ____ is less common. A. 16:1(9) B. 16:0 C. 18:1(9)

Answer 48

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

Question 49

esterified FA become ____ TAG molecules

Answer 49

neutral

Question 50

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

Answer 50

TAG

Question 51

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

Answer 51

glycerol phosphate and acyl CoA

Question 52

_____ is the initial acceptor of activated FA during TAG synthesis

Answer 52

Glycerol Phosphate

Question 53

What are the two pathways to produce glycerol phosphate?

Answer 53

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

Question 54

Free Fatty acid conversion to acetyl CoA is catalyzed by __________

Answer 54

fatty acyl CoA synthase (thiokinase)

Question 55

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

Answer 55

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

Question 56

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

Answer 56

Adipose Tissue

Question 57

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

Answer 57

Liver

Question 58

deliver exogenous dietary acquired lipids

Answer 58

chylomicrons

Question 59

____ deliver de novo synthesized lipids

Answer 59

VLDL