Lecture 28

Question 1

What is the major source or carbon for fatty acid synthesis?

Answer 1

Dietary Carbohydrates

Question 2

Fatty acid synthesis requires coordination between _____ and ____ reactions

Answer 2

cytosolic

Mitochondrial

Question 3

Where does fatty acid synthesis occur in the human body? (determine which area is the primary area for this)

Answer 3

Primarily in the liver, but also in adipose tissue (brain, kidneys, lactating mammary glands

Question 4

What is the precursor for FA synthesis? how many carbons are in this precursor and compare that the the number of carbons in the FAs it is used to create

Answer 4

Acetyl-CoA, which is a 2 carbon molecule

FAs have many more carbons

Question 5

State the 3 phases of FA synthesis and include the locations within the cell where these steps occur

Answer 5

Phase I: Cytosolic entry of Acetyl CoA
Made in mito matrix (but is needed in the cytoplasm)

Phase II: Generation of Malonyl CoA
Occurs in cytoplasm

Phase III: FA chain formation
Occurs in cytoplasm

Question 6

What is the rate limiting step of FA synthesis?

Answer 6

Generation of Malonyl CoA from Acetyl CoA

Question 7

What enzyme catalyzes the 7 reactions that must occur to carry out phase III of FA synthesis

Answer 7

FA synthase incorporates Acetyl CoA and Malonyl CoA into larger FA molecules

Question 8

State the 2 enzymes that are used to make Acetyl CoA in order to carry out phase I of FA synthesis (one in mito and one in cytoplasm) and state the metabolic pathway each enzyme is associated with

Answer 8

Citrate Synthase: part of the TCA cycle that occurs in the mito

ATP citrate lyase: part of glycolysis that occurs in the cytoplasm

(Basically opposites of each other)

Question 9

Describe the 6 steps that occur during phase I (cytosolic entry of Acetyl CoA) of FA synthesis

Answer 9

1. Citrate synthase catalyzes condensation of Acetyl CoA with Oxaloacetate (OAA) to from citrate
2. Citrate Transporter moves Citrate from mito to cytosol
3. Citrate Lyase converts Citrate BACK into Acetyl CoA and OAA
4. Malate dehydrogenase reduces OAA to Malate (Acetyl CoA is used to synthesize FAs)
5. Malate-alpha ketoglutarate transporter moves malate into the mito where it is oxidized BACK to OAA by “Malate dehydrogenase”
6. Malic enzyme converts cytosolic malate into pyruvate.
   A Pyruvate transporter then moves pyruvate into the mito where “pyruvate carboxylase” carboxylates it to OAA

Question 10

State the rate limiting enzyme of FA synthesis, include the phase of FA synthesis this enzyme is involved in, and describe the reaction that occurs (include other substances that are necessary)

Answer 10

Acetyl CoA Carboxylase (ACC) is the rate limiting enzyme of FA synthesis and it is involved in Phase II

ACC adds CO2 to Acetyl CoA (2 carbon molecule) to form Malonyl CoA (3 carbon molecule)

Biotin is a cofactor for the ACC reaction and ATP is needed to supply energy

Question 11

ACC exists in dimeric (___) or polymeric (_____) forms. (active or inactive)

Answer 11

Dimeric (inactive)

Polymeric (active)

Question 12

Malonyl CoA prevents FA _____ and _____ from occurring simultaneously. Malonyl acts as both a Substrate and a Regulator. explain this.

Answer 12

synthesis

degradation

Malonyl CoA is a substrate for FAS (FA synthase)

Malonyl CoA acts as a regulator by inhibiting carnitine acyltransferase (rate limiting step in FA degradation)

Question 13

Describe the function of the FAS complex and what is ultimately formed

Answer 13

FA synthesis reactions occur in the FAS complex

Malonyl CoA (2 carbons) molecules are added into a growing FA chain 7 TIMES in order to form Palmitate (16 carbons)

(7 reactions happening here makes sense bc 2+(7*2) = 16)

Question 14

Describe the structure of the FAS complex, the arrangement of it’s components

Answer 14

FAS is a multi-enzyme complex composed of 2 identical dimers

The Dimers are arranged in a “head to tail” conformation

Question 15

For the FAS complex, state the 2 characteristics it uses for adding Malonyl CoA subunits together to form FA chains. Describe how these interact.

Answer 15

1. 7 enzymes (each with their own reactions)
2. Acyl Carrier Protein (ACP)
   Has a flexible arm that facilitates the delivery of the substrate between the 7 enzymes

Question 16

What is the “phosphopantetheine group”?

Answer 16

Phosphopantetheine group: the end of the ACP “arm” that grabs onto the substrate

Question 17

State the Stoichiometric reaction for the synthesis of palmitate (you can omit the hydrogens but include NADPH)

Answer 17

1 Acetyl CoA + 7 Malonyl CoA + 14 NADPH = 1 Palmitate + 8 CoA + 14 NADP+

Question 18

Compare the functions of the Cys-SH and Pan-SH parts of FAS when it comes to making FAs

Answer 18

once the initial step of Acetyl CoA + Malonyl CoA yields a 4 carbon molecule, the longer chain of carbons attaches to the Cys-SH portion of FAS while the incoming Malonyl CoA is loaded onto the Pan-SH portion of FAS

Question 19

Describe the following reactions catalyzed by FAS

Condensation:

Reduction:

Dehydration:

Reduction:

Answer 19

Condensation: The Acetyl CoA and Malonyl CoA forming the initial bond
Releases ACP + CO2

Reduction: reduces one of the =O groups (turns beta-ketoacyl group to beta-hydroxyl group)
Consumes NADPH

Dehydration: water is lost (forms trans-enone group)

Reduction: reduces a C=C bond to form the 4 carbon molecule that all other Malonyl CoAs will be added to
Consumes NADPH

Question 20

State the 2 sources of NADPH that are used in the synthesis of Palmitate

Answer 20

Malic enzyme: 1

Pentose Phosphate Pathway: 2-12

Question 21

NADPH to NADP+ is a _______ reaction, whereas NADP+ to NADPH is a ______ reaction.

Answer 21

Oxidation (Reduction for whatever is receiving the electrons)

Reduction (Oxidation for whatever is losing the electrons)

Question 22

State the enzyme that represents the regulation point for all 3 phases of FA synthesis.

Answer 22

Phase I: ATP Citrate lyase

Phase II: Acetyl CoA Carboxylase (rate limiting step)

Phase III: FAS

Question 23

ATP citrate Lyase is ____ by phosphorylation. Also state the molecules that induce gene expression of ATP Citrate Lyase and the 2 things that counteract this gene expression.

Answer 23

Stimulated

Gene expression is induced by Glucose and Insulin

Gene expression is countacted by PUFAs (polyunsaturated FAs) and Leptin

Question 24

For ACC activity, state the 2 allosteric regulations and the dietary choice that induces an up regulation of it’s gene expression

Answer 24

Allosteric:
Citrate (+)
Long Chain Fatty Acids ex. Palmitate (-)

Induction:
High carb/low fat diet causes an upregulation in the ACC gene

Question 25

For the following hormones, state whether they stimulate or inhibit the activity of ACC and state the protein they operate through.

Insulin:

Epinephrine;

Glucagon:

AMP:

Answer 25

Insulin: activates ACC
via Protein phosphatase

Epinephrine: Inhibits ACC
via protein kinase A

Glucagon: Inhibits ACC
via protein kinase A

AMP: Inhibits ACC
via AMP kinase (energy sensor)

Question 26

Describe the allosteric regulation effect on FAS activity that the presence of phosphorylated sugars has. For the following conditions, state whether they will increase or decrease synthesis of FAS.

Insulin and Glucocorticoid hormones:

High carb/low fat diets:

High fat diets:

High PUFA:

Answer 26

Allosteric effect: the presence of phosporylated sugars increases FAS activity

Insulin and Glucocorticoid hormones: increase FA synthesis

High carb/low fat diets: increases FA synthesis

High fat diets: decreases FA synthesis

High PUFA: decreases FA synthesis

Question 27

Once Palmitate is synthesized, explain where longer chain FAs are synthesized and what molecules they use as carbon donors. What specific cells in the body NEED longer chain FAs?

Answer 27

Palmitate is converted into longer chain FAs in the SER and Mito

SER uses Malonyl CoA as a carbon donor
Mito uses Acetyl CoA as a carbon donor

Brain cells NEED longer chain fatty acids

Question 28

Define Desaturation, list how many desaturases humans have, and explain the limitations of human desaturases.

Answer 28

Desaturation: the introduction of double bonds into a FA

Humans have 4 desaturases (4, 5, 6, and 9)

Humans cannot synthesize FAs with double bonds beyond carbon 9 and 10 (hence the need for essential FAs)

Question 29

Where in the cell does desaturation occur, what specific enzyme does this, and what other molecule does it need?

Answer 29

Desaturation occurs in the SER

Acyl CoA Desaturases use NADPH (or NADH) and Oxygen to conduct desaturation

Question 30

Describe the mechanism the SER uses to desaturate FAs.

Answer 30

1. NADH becomes NAD+, and it’s electrons are passed through 3 enzymes
2. NADH-cytochrome b5 reductase (E-FAD to E-FADH2) has the electron first
3. Cytochrome b5 (Fe2+ to Fe3+) has the electron 2nd
   (Fe2+ = ferrous ; Fe3+ = Ferric)
4. Stearoyl CoA desaturase uses the electron on Stearoyl CoA + O2 to create Oleoyl CoA + 2H2O
   (“stearoyl” will be replaced with whatever other FA is being desaturated)

Question 31

State the Unsaturated FA that Linoleic acid is used to synthesize. State the 2 Unsaturated FAs that Linolenic acid is used to synthesize.
What to Linoleic and Linolenic acid have in common?

Answer 31

Linoleic acid is used to make arachidonic acid

Linolenic acid is used to make EPA (Eicosapentaenoic acid) and DHA (docosahexaenoic acid )

Both linoleic and linolenic acid are essential FAs (due to their omega 6 and 3’s respectively)

Question 32

Nomenclature of FAs is based on what?

Answer 32

the position of the nearest double bond carbon from the methyl (omega) end

Question 33

What are Triacylglycerols and what subunits compose them?

Answer 33

Triacylglycerols are the storage form of lipids that are composed of FA subunits

Question 34

______ is the major precursor for several classes of Eicosanoid hormones (signalling molecules. State 4 examples of these Eicosanoid hormones.

Answer 34

Arachidonate

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Eicosanoid hormones:
PGs (Prostaglandins
Prostacyclins
Thromboxanes
Leukotrienes
“Paul george Passes To Lin”)
~~~

Question 35

Describe the molecular structure of a PG. What 2 enzymes modify these to yield the 9 different classes of PGs?

Answer 35

20 carbon FA containing a 5 carbon ring

reductases and isomerases

Question 36

What are the following characteristics consistent with?

Stimulate inflammation
Regulate blood flow to particular organs
Control ion transport across the membrane
Modulate synaptic transmission
Induce sleep

Answer 36

PG’s (Prostaglandins)

Stimulate inflammation
Regulate blood flow to particular organs
Control ion transport across the membrane
Modulate synaptic transmission
Induce sleep