FA Synthesis

Question 1

In humans, the ___ is the main site for FA synthesis

Answer 1

liver

note: other sites include: kidney, brain, lung, mammary gland, and adipose

Question 2

The process of FA synthesis occurs in what part of the cell?

Answer 2

cytoplasm

Question 3

FAs are synthesized from 2 carbon units (acetyl-CoA). ___ is the main source of the acetyl-CoA, with some contribution from ___

Answer 3

glucose; AAs

note: other cofactors/substrates include: NADPH, ATP, biotin, and HCO3-

Question 4

The process of using acetyl CoA to produce FA in the cytosol requires two important enzymes. What are they?

Answer 4

1. acetyl CoA carboxylase

2. FA synthase

Question 5

When glucose is plentiful, glycolysis in the liver will produce “excess” ___ which enters mitochondria and produces ___-___ for the TCA cycle

Answer 5

pyruvate; acetyl-CoA

note: citrate, which is not further metabolized by the TCA can exit the mitochondria

Question 6

In the cytosol, citrate is the substrate for ATP citrate lyase. What does this enzyme do? What does it require?

Answer 6

citrate is split back to oxaloacetate and acetyl-CoA

ATP is required

note: this enzyme is inducible

Question 7

Cytosolic malate dehydrogenase reduces ___ to malate

Answer 7

OAA

Question 8

What does the Malic enzyme do?

Answer 8

1. converts malate to pyruvate
2. produces NADPH which is necessary for FA synthesis

note: this enzyme is inducible

Question 9

Acetyl-CoA carboxylase catalyzes the reaction producing ___-___ from acetyl-CoA

Answer 9

malonyl-CoA

Question 10

Acetyl-CoA carboxylase requires ___ and is the rate-limiting enzyme of ___ ___

Answer 10

biotin; FA synthesis

Question 11

Acetyl-CoA carboxylase is the regulated step of FA synthesis. It exists as either inactive ___ __ or as active ___.

Answer 11

proteomeric dimers; polymers

Question 12

Acetyl-CoA carboxylase is stimulated by what? inhibited by what?

Answer 12

stimulated by citrate (feed forward)

inhibited by long-chain fatty acyl-CoA (feed back)

Question 13

Acetyl-CoA carboxylase is also controlled by phosphorylation/dephosphorylation. True or false?

Answer 13

true

note: an AMP-dependent protein kinase phosphorylates the enzyme

Question 14

Phosphorylation causes ___ of acetyl-CoA carboxylase?

Answer 14

inactivation

Question 15

In regards to acetyl-CoA carboxylase, AMP would increase during times of ____

Answer 15

fasting

Question 16

Glucagon stimulates the activity of the AMP-dependent kinase, which results in ___ of FA synthesis

Answer 16

inhibition

note: mechanism via cAMP-dependent protein kinase

Question 17

A protein phosphatase dephosphorylates acetyl-CoA carboxylase. This causes ___ of the enzyme. This protein phosphatase is stimulated by ___

Answer 17

activation; insulin

Question 18

Prolonged consumption of a diet containing excess calories results in increased synthesis of this enzyme

Answer 18

acetyl-CoA carboxylase

note: a low-calorie diet reduces synthesis of this diet

Question 19

FA synthase is a multi-functional enzyme in eukaryotes. It is active as a ___. Each monomer contains ___ different enzymatic activities.

Answer 19

dimer; 7

Question 20

FA synthase allows only one fatty acyl chain to be synthesized at a time. True or false?

Answer 20

false; two fatty acyl chains

Question 21

FA synthase sequentially adds two-carbon units from ___-___ to a growing ___ ___ chain

Answer 21

malonyl-CoA; fatty acyl

Question 22

The starting unit of FA synthase is ___-___ and the product is ____

Answer 22

acetyl-CoA; palmitate

Question 23

1. In the first round of the synthesis cycle, acetyl transacylase adds an acetyl group to the ___ of a cysteine residue of ketoacyl synthase domain of one monomer

Answer 23

SH

Question 24

2. Malonyl transacylase adds a malignly group to the SH of the ____-___ group of acyl carrier protein (ACP) domain of the other monomer

Answer 24

phospho-pantetheine

Question 25

3. 3-ketoacyl synthase catalyzes the FA synthase reaction adding the acetyl group to the malignly group and decarboxylation, leaving the product (a 3-ketoacyl group) bout the the ___ domain

Answer 25

ACP

Question 26

4. 3-ketoacyl reductase reduces the 3-keto group to an hydroxyl, using ___ as the reducing agent

Answer 26

NADPH

Question 27

5. The hydrates catalyzes the removal of H2O resulting in a ___-___ group

Answer 27

2-enoyl

Question 28

6. The enoyl reductase saturates the carbon-carbon double bond to produce a saturated acyl group (2 carbons longer) using ___ as the reducing agent

Answer 28

NADPH

Question 29

7. The lengthened acyl group is transferred from the ACP domain to the opposite monomers ____ ____ cysteine residue for another round

Answer 29

ketoacyl synthase

note: for each round, 2 carbons are added from malonyl-CoA

Question 30

8. A total of 7 rounds is completed to form a palmitoyl group. After the 7th round, the _____ hydrolyzes the palmitate from the ACP domain

Answer 30

thioesterase

Question 31

In order to be further metabolized, the palmitate is converted to palmitoyl-CoA for what 4 things?

Answer 31

1. esterfircation to triacylglycerols
2. elongation
3. desaturation
4. esterfication to cholesteryl ester

Question 32

Give the 2 steps of the overall equation for palmitate synthesis

Answer 32

1. from acetyl-CoA and malonyl-CoA

2. from acetyl-CoA to palmitate - must account for ATP used by acetyl-CoA carboxylase

Question 33

The major source of NADPH is the ___ ___ pathway with some provided by magic enzyme

Answer 33

pentose phosphate

Question 34

FA elongation occurs primarily in the ____ ___

Answer 34

endoplasmic reticulum

Question 35

The preferred substance of FA elongation is ____-___. The preferred product is ____-___

Answer 35

palmitoyl-CoA; stearoyl-CoA (18:0)

Question 36

The formation of mono-unsaturated FAs begins with stearoyl-CoA desaturase which is an enzyme of the ER that requires what?

Answer 36

NADH or NADPH, molecular O2, cytochrome b5

Question 37

In regards to stearoyl-CoA desaturase, the desaturation always occurs at carbon ___

Answer 37

9

Question 38

The product of stearoyl-CoA denatures is what?

Answer 38

oleoyl-CoA or palmitoleoyl-CoA

Question 39

Poly-unsaturated FAs have 2 important functions. What are they?

Answer 39

1. increase membrane fluidity

2. source of important bio-active compounds (eicosanoids)

Question 40

Formation of PUFAs depends on chain ____ and introduction of ___ bonds

Answer 40

elongation; double

Question 41

Humans cannot introduce a double bond beyond carbon ___

Answer 41

9

Question 42

FAs derived from oleic acid are referred to as w-9 or n-9. Why?

Answer 42

because the first double bond encountered rom the w or n carbon is 9 carbons toward the carboxyl carbon

Question 43

Since humans cannot add double bonds beyond carbon 9, some FAs are required in the diet. Name 2 of these.

Answer 43

w-6 FA: linoleic acid is an essential FA

w-3 FA: alpha-linolenic acid is an essential FA

Question 44

Synthesis of ____ acid is an example of synthesis of an important PUFA from an essential FA

Answer 44

arachidonic