Fatty Acid Degradation - General

Question 1

How are fatty acids stored in adipose tissue?

Answer 1

They are stored in the form of triacylglycerol.

Question 2

The degradation of fatty acids is called what?

Answer 2

Beta oxidation.

Question 3

Oxidation of fatty acids generates _____ ATP than the oxidation of glucose. Why?

Answer 3

More. Fatty acids are far more reduced, thus possessing more electrons to donate to the ETC.

Question 4

Where does beta oxidation occur in the cell? What advantage does this location allow?

Answer 4

In the mitochondrial matrix. The acetyl CoA produced from beta oxidation can directly enter the citric acid cycle.

Question 5

Fatty acid degradation relies on the presence of _____. Therefore, the process is an _____ process. Because of this, fatty acids are a (more/less) versatile energy source.

Answer 5

Oxygen. Aerobic. Less.

Question 6

What are the three stages of fatty acid degradation?

Answer 6

1. Triacylglycerol breakdown
2. Fatty acids are released into the blood and are transported into the cytosol, then the mitochondrial matrix
3. The specific reactions of beta oxidation occur

Question 7

Briefly describe the structure of a fatty acid. What is the common length?

Answer 7

Non polar, long hydrocarbon chain with a carboxylic acid group on the end. They are commonly 12-20 carbons in length.

Question 8

If a fatty acid has double bonds it is said to be _____. What configuration are most double bonds in? If it has multiple double bonds it is ______.

Answer 8

Unsaturated. Most are in the cis (substituents on each side are on the same side) configuration. Polyunsaturated.

Question 9

Numbering of fatty acids starts where? The 2nd and 3rd carbons are termed what?

Answer 9

Numbering starts at the carboxylic acid carbon. The 2nd and 3rd carbons are called the alpha and beta carbon respectively.

Question 10

A double bond will have what effect on boiling point?

Answer 10

It will decrease boiling point.

Question 11

How is a double bond named?

Answer 11

It is denoted using ∆ accompanied by a number indicating the position of the first carbon that is part of the double bond.

Question 12

What are the two factors that make adipose tissue a very important tissue in the body? Many severe metabolic diseases come as a result of having too _____ adipose tissue.

Answer 12

1. Storage of an important fuel
2. Secretion of adipokines which control overall metabolism and appetite.

Little.

Question 13

What is the structure of triacylglycerol? What bond attaches the components?

Answer 13

Three fatty acids linked via ester bonds to a glycerol backbone.

Question 14

What reaction separates the fatty acids from the glycerol backbone in the first step of fatty acid breakdown? How many enzymes are used and what enzymes are the key ones? What are they stimulated by and what does stimulation set off?

Answer 14

A hydrolysis reaction on each fatty acid (3 water molecules). 3 lipases are used, 2 key ones:

1. Adipose triglyceride lipase (ATGL): acts on triacylglycerol.
2. Hormone sensitive lipase (HS-lipase): acts on diacylglycerol.

These lipases are activated by epinephrine and glucagon, which both set off cAMP signalling cascades, activating PKA, which activates ATGL and HS-lipase.

Question 15

What does activation of HS-lipase and ATGL by hormones ensure?

Answer 15

Controlled activation ensures that the body only breaks down triacylglycerol when the body is low on energy supply.

Question 16

What transports fatty acids in the blood?

Answer 16

A blood protein called albumin.

Question 17

Where is glycerol taken up in the body? What happens when it is taken up? What can this product be used towards? What is it typically used towards?

Answer 17

In the liver. It is converted to dihydroxyacetone phosphate. DHAP can be directed towards glycolysis or gluconeogenesis, but is typically directed towards gluconeogenesis as the body needs more fuel during degradation.

Question 18

How do fatty acids enter the cell?

Answer 18

They bind to proteins on the cell surface and are shuttled in.

Question 19

What must happen for fatty acids to enter the intermembrane space of the mitochondria?

Answer 19

They must be activated and shuttled into the mitochondria by coenzyme A on the outer mitochondrial membrane. ATP is consumed producing AMP and PP_i, which is then degraded to 2 P_i. This produces Acyl CoA.

Question 20

How can Acyl CoA get across the inner mitochondrial membrane? What enzymes are involved for both directions of the reaction?

Answer 20

To get across the inner mitochondrial membrane Acyl CoA is combined with carnitine, and converted to acyl carnitine by carnitine acyltransferase I, which is able to be transported by a special transferase. The reverse reaction is catalyzed by carnitine acyltransferase II, and the free carnitine is shuttled back into the cytosol.

Question 21

Which carbon is oxidized during each round of beta oxidation?

Answer 21

The third (beta) carbon.

Question 22

What is the 1st reaction of the 3rd stage of beta oxidation? What enzyme is involved?

Answer 22

This is an oxidation reaction. The bond between the alpha and beta carbons become oxidized to a double bond by acyl CoA dehydrogenase, and the electrons are used to reduce FAD to FADH₂. The double bond is in the trans configuration.

Question 23

What is the 2nd reaction of the 3rd stage of beta oxidation? What enzyme is involved?

Answer 23

It is a hydration reaction. Water is added across the double bond, which puts an –OH on the β-carbon, and a hydrogen on the α-carbon. The product is 3-hydroxyacyl CoA since the hydroxyl is on the number 3, or β, carbon. The enzyme that catalyzes this reaction is enoyl CoA hydratase.

Question 24

What is the 3rd reaction of the 3rd stage of beta oxidation? What enzyme is involved?

Answer 24

It is an oxidation reaction. 3-hydroxyacyl CoA is oxidized by β-hydroxyacyl CoA dehydrogenase to form 3-ketoacyl CoA and NAD⁺ becomes reduced to NADH, which can donate its electrons to the electron transport chain.

• Note that the β-carbon now is fully oxidized, having started out as a CH₂ and is now a C=O.

Question 25

What is the 4th reaction of the 3rd stage of beta oxidation? What enzyme is involved?

Answer 25

A two-carbon unit is cleaved off the end of the 3-ketoacyl CoA, which is an acetyl CoA unit. This cleavage is achieved using free CoA, with the –SH group attacking the bond between the α and β-carbon, giving the second product, acyl CoA, which is two carbons shorter than what was started with. This reaction is done by **thiolase** or **3-ketoacyl thiolase**.

Question 26

Once the final part of the 3rd step of beta oxidation is complete and the 2 carbon acetyl CoA is cleaved off, what happens to the remaining part of the fatty acid? When does this continue until?

Answer 26

This goes through the four reactions above again, releasing yet another acetyl CoA. When the acyl CoA is degraded to a four-carbon unit, the final round of β-oxidation releases two acetyl CoA and completes the β-oxidation.

Question 27

How many rounds of oxidation are required to completely oxidize palmitate? What is the gross and net ATP production?

Answer 27

7 rounds. 108 ATP are generated and 2 are used, giving a net production of 106 ATP.

Question 28

What does malonyl CoA regulate and what effect is it? Why does this make sense logically?

Answer 28

Malonyl CoA is a potent inhibitor of carnitine acetyltransferase. This makes sense as high levels of malonyl CoA are observed during fatty acid synthesis. This inhibition would lead to a decrease in fatty acid transport into the mitochondria and therefore decreased β-oxidation.

Question 29

What issue would an unsaturated fatty acid cause for oxidation? How is this resolved?

Answer 29

Once encountering a double bond, the product created will have it's double bond in the cis configuration, which is not a substrate for the first enzyme in β-oxidation (acyl CoA dehydrogenase). This is resolved using an **isomerase**, which converts the cis double bond to a trans double bond between carbons 2 and 3. This results in a normal intermediate of β-oxidation and thus β-oxidation continues onward.

Question 30

What issue would an polyunsaturated fatty acid cause for oxidation? How is this resolved?

Answer 30

Like with an unsaturated fatty acid, polyunsaturated fatty acids are not compatible with the first enzyme of β-oxidation. Again, an **isomerase** is used, along with a **reductase**.

Question 31

What issue do odd-chain fatty acids cause for β-oxidation? How is this issue resolved and what is the final product?

Answer 31

In the last round of β-oxidation, rather than two acetyl CoA molecules being produced, one acetyl CoA and a 3-carbon acyl CoA called propionyl CoA is produced. Propionyl CoA is carboxylated at carbon 3, generating a four-carbon molecule called **D-methylmalonyl CoA**. This undergoes an intramolecular rearrangement to the L-isomer, catalyzed by **methylmalonyl CoA mutase**, a vitamin B₁₂-containing enzyme. The final product of this pathway is **succinyl CoA**, which can enter the citric acid cycle.

Question 32

While most of the acetyl CoA produced from β-oxidation enters the citric acid cycle, a small portion of the acetyl CoA in the liver is used to synthesize \_\_\_\_\_. How many types are produced, what are the names, and where and how does this process occur?

Answer 32

Ketone bodies. 3 types are produced: 1. 3-hydroxybutyrate (also called β-hydroxybutyrate) 2. Acetoacetate 3. Acetone This pathway occurs in the mitochondrial matrix and uses two acetyl CoA molecules to synthesize acetoacetate, which is then converted enzymatically to 3-hydroxybutyrate or to acetone, through a spontaneous decarboxylation.

Question 33

What is important about ketone bodies in terms of being an energy source?

Answer 33

Ketone bodies are an important and useful fuel molecule since they are water soluble, and _they can be used as fuel by the brain_ while fatty acids cannot be due to their inability to cross the blood brain barrier. Other tissues such as heart and kidney may even use ketone bodies preferentially over glucose.

Question 34

When would ketone body synthesis increase tremendously?

Answer 34

Under starvation conditions and in uncontrolled diabetes.

Question 35

How are ketone bodies degraded?

Answer 35

3-Hydroxybutyrate and acetoacetate are metabolized to acetyl CoA which can enter the citric acid cycle, and acetone is exhaled through the lungs, as it is far less abundant and volatile.

Question 36

What is the liver unable to do in regards to the conversion of ketone bodies? What does this ensure?

Answer 36

The liver lacks the CoA transferase and thus cannot convert acetoacetate to acetoacetyl CoA. This ensures that the liver itself doesn’t use up the acetoacetate that it produces, but instead exports it to other tissues via the blood.

Question 37

Which ketone body has a regulatory role in fatty acid metabolism? What is its role?

Answer 37

Acetoacetate. High levels of acetoacetate, which indicates an abundance of acetyl CoA, act on adipose tissue to inhibit lipolysis.

Question 38

_Clinical Insight_: Diabetes and Ketone Production 1. What effect does poorly managed diabetes have on ketone production? 2. What does this cause? 3. What effect does this have on the body?

Answer 38

1. Oxaloacetate stores are depleted, and insulin is not present, causing excessive production of acetyl CoA, which is then converted to ketone bodies. 2. Ketone bodies are acidic, so it causes ketoacidosis. 3. This inhibits the CNS, causing confusion, poor motor control, coma, and death. The patient will often present intoxicated, as ketoacidosis causes symptoms of drunkeness, while acetone is also released by the lungs, which smells like alcohol.