Fatty Acid Metabolism 1 - Synthesis

Question 1

__________ is a hormone that acts as a satiety signal, telling you to stop eating when you’re full, and increases your energy expenditure. Knockout mice become obese.

Answer 1

Leptin

Question 2

Name the molecule utilized as the 2-carbon donor in lipid metabolism. What kind of bond does it have?

Answer 2

Acetyl CoA

Thioester bond

Question 3

Acetyl CoA is derived from _________ acid and contains a ______ group capable of forming __________ bonds

Answer 3

Acetic

Thiol

Thioester

Question 4

In order to begin the process of fatty acid synthesis, you need Acetyl CoA from the ____________, and ___________from the PPP in the cytosol

Answer 4

Mitochondria

NADPH

Question 5

What are some of the general functions of lipids?

Answer 5

Fuel stores
Plasma membrane structure
Signaling molecules
Heat generation

Question 6

In terms of the classification of lipids, there are two possible types of derivatives. What are they?

Answer 6

Fatty acid derivatives (contain FA’s)

Isoprene derivatives (made up multiple isoprene units, includes vitamins, hormones, CoQ, etc.)

Question 7

In terms of fatty acid derivatives of lipids, ___________ are your mono-, di-, and triacylglycerols because they have a glycerol backbone

Answer 7

Glycerolipids

Question 8

In terms of fatty acid derivatives of lipids, ___________ consist of 2 fatty acids attached to a glycerol backbone and a phosphate esterified with a head group

Answer 8

Glycerophospholipids

Question 9

In terms of fatty acid derivatives of lipids, ___________ contain ceramide (a fatty acid attached to a sphingosine), as well as a phosphate attached to the sphingosine and esterified to an amino or sugar alcohol (i.e., sphingomyelin)

Answer 9

Sphingophospholipids

Question 10

In terms of fatty acid derivatives of lipids, ___________ contain ceramide with an oligosaccharide attached (these are also known as glycolipids)

Answer 10

Glycosphingolipids

Question 11

In terms of fatty acid derivatives of lipids, ___________ are derived from 20-carbon arachidonic acid (i.e., prostaglandins, thromboxanes, and leukotrienes)

Answer 11

Eicosanoids

Question 12

What do all lipids have in common, and is especially notable for lipid soluble vitamins A, D, E, and K?

Answer 12

Isoprene unit

Question 13

Fatty acid synthesis primarily occurs in the _________, but also occurs in _________ tissue, brain, and kidneys.

It involves the use of acetyl CoA to form C16 _________ acid.

It requires coordination between ___________ and cytosolic reactions.

The main location for FA synthesis is the ____________

Answer 13

Liver; adipose tissue

Palmitic

Mitochondrial

Cytoplasm

Question 14

Acetyl CoA acts as the carbon source for fatty acid synthesis, but since the majority of lipogenesis occurs in the cytoplasm, it must be transported from the mitochondria to the cytosol in the form of __________ via the _____________ ______________

Answer 14

Citrate

Citrate shuttle

Question 15

True or false: the transfer of acetyl coA from the mitochondria to the cytosol is ATP-dependent

Answer 15

True

Question 16

The citrate shuttle is used to transport acetyl CoA from mitochondria to cytosol in an energy dependent process. The other primary function of the citrate shuttle is to do what?

Answer 16

Regenerate Oxaloacetate (TCA intermediate) in the mitochondrial matrix

Question 17

What is the rate limiting step of fatty acid synthesis?

Answer 17

Acetyl CoA –> Malonyl CoA (Carboxylation)

Enzyme = acetyl CoA carboxylase aka ACC (requires biotin)

Question 18

The purpose of the rate limiting step of fatty acid synthesis is for ACC to add a ______ to acetyl CoA, which requires _________ and _________

Answer 18

CO2
Biotin
ATP

Question 19

Malonyl CoA is formed in the rate limiting step of fatty acid synthesis. It acts as a regulator in that it prevents synthesis and degradation from happening simultaneously. How does it do this?

Answer 19

It inhibits carnitine acyltransferase (the rate limiting enzyme in fatty acid degradation)

Question 20

What are the positive regulators for the rate limiting step of fatty acid synthesis?

Answer 20

Citrate and insulin

Question 21

What are the negative regulators for the rate limiting step of fatty acid synthesis?

Answer 21

Glucagon, epinephrine

High AMP

Palmitate

PUFA

Question 22

What enzyme is responsible for the serial additions of acetyl CoA to malonyl CoA to eventually form palmitate?

Answer 22

Fatty acid synthase

Question 23

What are the positive and negative regulators of fatty acid synthase?

Answer 23

(+) Insulin, glucocorticoids

(-) PUFA

Question 24

If palmitate is 16 carbons, how many acetyl CoA’s are required to build it, and how many rounds of synthesis must take place?

Answer 24

8 acetyl CoAs, 7 rounds of synthesis

Question 25

The synthesis of TAGs from ingested fatty acids requires the action of what enzyme to act on the chylomicrons containing VLDLs?

Answer 25

Lipoprotein lipase

Question 26

Lipoprotein lipase acts on ingested fats in the form of chylomicrons to release free fatty acids. These combine with ___________ which is shunted to TAG synthesis from glycolysis using ______________ enzyme

Answer 26

Glycerol 3P; Glycerol 3P dehydrogenase

Question 27

Once fatty acids combine with a glycerol-3P, they go through steps to build a ________, then a TAG, which is stored in _____________

Answer 27

DAG

Adipocytes

Question 28

What effect do glucose and insulin have on ATP citrate lyase? What counteracts this effect?

Answer 28

Gene expression of ATP citrate lyase is induced by glucose/insulin

This can be counteracted by leptin or PUFAs

[note that ATP citrate lyase can also be stimulated by phosphorylation]

Question 29

Where is the leptin receptor expressed?

Answer 29

In the hypothalamus

Question 30

What happens when a leptin knockout mouse is given leptin?

Answer 30

The obese mouse will lose weight

Question 31

If insulin is present, will ACC be in the phosphorylated or dephosphorylated form?

Answer 31

DEphosphorylated

If insulin is present, we are in a fed state, so energy storage and FA synthesis will be stimulated

Thus, ACC will be in its active state. ACC is activated by a protein phosphatase (which removes the phosphate group)

Question 32

Insulin upregulates the protein phosphatase responsible for activating ACC by removing its phosphate group.

How does epinephrine or glucagon affect ACC?

Answer 32

Epinephrine or glucagon upregulates cAMP-dependent protein kinase A (AMPK), which inhibits protein phosphatase so the phosphate remains on ACC and it remains inactive (fatty acids will not be synthesized because the body is in a fasting state)

Question 33

How is ACC affected by citrate?

Answer 33

ACC is allosterically stimulated by citrate

Citrate is present when both acetly CoA and ATP are abundant, signaling the body to store energy

Inactive ACC exists as an isolated dimer, and citrate facilitates the polymerization, thus partially reversing the inhibition produced by phosphorylation

[note that the dephosphorylated form of ACC is highly active irrespective of citrate levels]

Question 34

How does palmitoyl CoA (aka long chain acyl CoA) affect ACC?

Answer 34

Causes it to disassemble into the inactive form

[also inhibits the citrate shuttle and glucose 6-phosphate dehydrogenase)

Question 35

Fatty acid synthase is a __________ enzyme complex composed of 2 identical dimers. Each dimer has ____ separate enzymatic activities and an associated _______

Answer 35

Large

7

ACP (acyl carrier protein)

Question 36

What is the significance of fatty acid synthase existing as a symmetrical dimer?

Answer 36

Two fatty acids can be synthesized simultaneously

Question 37

There are 4 reactions of Fatty Acid Synthase, name each type in order

Answer 37

Condensation
Reduction
Dehydration
Reduction

Question 38

Elongation of FAs in the smooth ER pathway utilizes what as the carbon donor?

Answer 38

Malonyl CoA

Question 39

What is desaturation of FAs, where does it occur, and what enzyme catalyzes it?

Answer 39

Desaturation is the introduction of double bonds, and it occurs in the smooth ER (SER)

Requires NADPH and oxygen, and is catalyzed by acyl CoA desaturase enzymes

Question 40

Fatty acids with double bonds beyond carbon ____ and ____ cannot be synthesized in humans, so they need to be ingested in the diet

Answer 40

9 and 10