Lipid Catabolism

Question 1

What is the primary energy-yielding pathway from fatty acids, and why is it significant?

Answer 1

Fatty acid oxidation is a central energy-yielding pathway that produces ATP in many organisms and tissues, providing around 40% of daily energy needs from dietary triacylglycerols (TAG) in industrialized countries.

Question 2

How are free fatty acids activated in the cytosol for catabolism?

Answer 2

Free fatty acids are activated by fatty acyl-CoA synthetase to form fatty acyl-CoA, a process that requires ATP. The enzyme attaches coenzyme A to the fatty acid.

Question 3

Why is the formation of fatty acyl-CoA energetically favorable?

Answer 3

The reaction is favorable due to the hydrolysis of two high-energy phosphodiester bonds, which releases AMP and two inorganic phosphate molecules, with a ΔG’º of -34 kJ/mol.

Question 4

What two main fates can fatty acyl-CoA have after activation in the cytosol?

Answer 4

Fatty acyl-CoA can either be transported into the mitochondria for oxidation (energy production) or used within the cytosol to synthesize membrane lipids.

Question 5

What role does coenzyme A play in fatty acid activation?

Answer 5

Coenzyme A makes the fatty acid more reactive by increasing free energy and serves as a good leaving group during nucleophilic attack, facilitating further metabolic reactions.

Question 6

Describe the reaction equation for fatty acid activation.

Answer 6

Fatty acid + CoA + ATP → fatty acyl-CoA + AMP + 2Pi

Question 7

How are fatty acyl-CoA molecules transported into mitochondria?

Answer 7

Fatty acyl-CoA destined for mitochondria binds to carnitine in the cytosol, creating fatty acyl-carnitine. This complex is then transported across the inner mitochondrial membrane via the acyl carnitine/carnitine cotransporter.

Question 8

What happens to fatty acyl-carnitine once it reaches the mitochondrial matrix?

Answer 8

In the mitochondrial matrix, carnitine transfers the fatty acyl group back to coenzyme A, reforming fatty acyl-CoA for beta-oxidation.

Question 9

Why is carnitine necessary for fatty acid transport into the mitochondria?

Answer 9

Carnitine facilitates the transfer of fatty acyl-CoA across the mitochondrial membrane, as fatty acyl-CoA alone cannot cross the inner mitochondrial membrane.

Question 10

In which cellular location does beta-oxidation of fatty acids occur?

Answer 10

Beta-oxidation of fatty acids occurs in the mitochondrial matrix.

Question 11

What are the three stages involved in the complete oxidation of fatty acids?

Answer 11

Stage 1 – Beta-oxidation: Fatty acids undergo oxidative removal of two-carbon units to form acetyl-CoA.
Stage 2 – Citric Acid Cycle: Acetyl-CoA is oxidized to CO₂.
Stage 3 – Oxidative Phosphorylation: Reduced electron carriers are oxidized in the electron transport chain, driving ATP synthesis.

Question 12

Describe the four key steps of the beta-oxidation pathway.

Answer 12

Oxidation: Dehydrogenation of fatty acyl-CoA forms a C=C bond between the alpha and beta carbons, producing trans-Δ²-enoyl-CoA, catalyzed by acetyl-CoA dehydrogenases.
Hydration: Water is added across the double bond to form L-beta-hydroxy-acyl-CoA, catalyzed by enoyl-CoA hydratase.
Oxidation: L-beta-hydroxyacyl-CoA is dehydrogenated to beta-ketoacyl-CoA, producing NADH and catalyzed by beta-hydroxyacyl-CoA dehydrogenase.
Thiolysis: Beta-ketoacyl-CoA reacts with free CoA to form acetyl-CoA and a shortened acyl-CoA, catalyzed by thiolase.

Question 13

What role does the beta carbon play in the beta-oxidation pathway?

Answer 13

The beta carbon becomes more reactive after the initial oxidation steps, allowing it to become a target for nucleophilic attack, which facilitates the formation of acetyl-CoA and the continuation of beta-oxidation.

Question 14

How many cycles of beta-oxidation are required to fully oxidize a 14-carbon fatty acid, and what is produced?

Answer 14

Six cycles are needed for a 14-carbon fatty acid, producing seven molecules of acetyl-CoA.

Question 15

What is the overall equation for one cycle of beta-oxidation of palmitoyl-CoA?

Answer 15

Palmitoyl-CoA(16C)+CoA+FAD+NAD⁺+H₂O→Myristoyl-CoA(14C)+Acetyl-CoA+FADH₂+NADH+H⁺

Question 16

Describe the overall oxidation process of palmitoyl-CoA to acetyl-CoA.

Answer 16

Palmitoyl-CoA (16C) undergoes seven cycles of beta-oxidation, requiring 7 CoA, 7 FAD, 7 NAD⁺, and 7 H₂O, producing 8 acetyl-CoA, 7 FADH₂, and 7 NADH + 7 H⁺.

Question 17

What is the complete equation for the beta-oxidation of palmitoyl-CoA, including ATP production?

Answer 17

Palmitoyl-CoA+7CoA+7O₂+28Pi+28ADP→8Acetyl-CoA+28ATP+7H₂O

Question 18

How is the net production of water accounted for in beta-oxidation?

Answer 18

During beta-oxidation, 7 molecules of water are used, but 14 are generated through oxidative phosphorylation, leading to a net production of 7 H₂O.

Question 19

How many ATP are generated from the complete oxidation of palmitate, and how does this compare to glucose oxidation?

Answer 19

The oxidation of palmitate yields a net gain of 106 ATP (108 ATP minus 2 ATP used for activation). In comparison, glucose yields about 30-32 ATP, depending on the transport method for NADH.

Question 20

How does acetyl-CoA generated from beta-oxidation contribute to further ATP production?

Answer 20

Acetyl-CoA enters the citric acid cycle, where additional NADH and FADH₂ are produced and subsequently oxidized in the electron transport chain, contributing to further ATP synthesis.

Question 21

What additional step is required for the oxidation of unsaturated fatty acids compared to saturated fatty acids?

Answer 21

The oxidation of unsaturated fatty acids requires an additional reaction to convert a cis double bond to a trans double bond. This allows beta-oxidation to continue.

Question 22

In the beta-oxidation of oleoyl-CoA (18:1(Δ9)), what occurs after the first three rounds of beta-oxidation?

Answer 22

After three rounds of beta-oxidation, oleoyl-CoA yields 3 acetyl-CoA and a molecule of cis-Δ3-dodecenoyl-CoA, with a cis double bond between the beta and gamma carbons.

Question 23

Why must the cis double bond in unsaturated fatty acids be converted to a trans double bond during beta-oxidation?

Answer 23

Beta-oxidation requires a trans double bond between the alpha and beta carbons. The cis double bond between the beta and gamma carbons must be converted to trans to continue oxidation.

Question 24

What enzyme is responsible for repositioning the double bond in unsaturated fatty acid oxidation, and what does it accomplish?

Answer 24

The enzyme Δ3,Δ2-enoyl-CoA isomerase repositions the double bond from a cis-Δ3 position to a trans-Δ2 position, creating trans-Δ2-dodecenoyl-CoA. This allows beta-oxidation to proceed.

Question 25

After the double bond is repositioned by Δ3,Δ2-enoyl-CoA isomerase, how many additional rounds of beta-oxidation occur in the oxidation of oleoyl-CoA?

Answer 25

Five additional rounds of beta-oxidation occur after the double bond is repositioned, ultimately producing a total of 6 acetyl-CoA molecules.

Question 26

How does the energy yield from unsaturated fatty acids compare to saturated fatty acids during beta-oxidation?

Answer 26

Unsaturated fatty acids yield slightly less ATP because they bypass the first oxidation step that would normally generate FADH₂. This reduces the number of reduced electron carriers produced.

Question 27

Why is there less ATP produced from the oxidation of unsaturated fatty acids?

Answer 27

Since the initial oxidation step of beta-oxidation (which produces FADH₂) is bypassed due to the presence of an existing double bond (created by isomerase), fewer reduced electron carriers are generated, resulting in less ATP.

Question 28

Where do odd-chain fatty acids typically originate, and are they synthesized in the human body?

Answer 28

Odd-chain fatty acids are not synthesized in the body; they are primarily derived from plant fats.

Question 29

How are odd-chain fatty acids oxidized compared to even-chain fatty acids?

Answer 29

Odd-chain fatty acids are oxidized through the same pathway as even-chain fatty acids, but their final cleavage yields one acetyl-CoA and one propionyl-CoA instead of two acetyl-CoA molecules.

Question 30

What is the final product of beta-oxidation in odd-chain fatty acids, and how does it differ from even-chain fatty acids?

Answer 30

The final product of odd-chain fatty acid oxidation is acetyl-CoA and propionyl-CoA, whereas even-chain fatty acids only produce acetyl-CoA.

Question 31

What happens to propionyl-CoA after it is produced in the beta-oxidation of odd-chain fatty acids?

Answer 31

Propionyl-CoA undergoes a series of three additional reactions in the mitochondrial matrix to be converted into succinyl-CoA, which enters the citric acid cycle.

Question 32

What occurs in the first step of propionyl-CoA metabolism?

Answer 32

Propionyl-CoA is carboxylated to form methylmalonyl-CoA.

Question 33

What is the role of epimerase in the metabolism of propionyl-CoA?

Answer 33

Epimerase converts D-methylmalonyl-CoA to its L-stereoisomer, preparing it for the next reaction.

Question 34

Describe the final reaction in the conversion of propionyl-CoA to a citric acid cycle intermediate.

Answer 34

L-methylmalonyl-CoA undergoes a rearrangement to form succinyl-CoA, which can then enter the citric acid cycle.

Question 36

What types of fatty acids are primarily processed in peroxisomes within mammals?

Answer 36

Peroxisomes are more active in processing long-chain and branched-chain fatty acids.

Question 37

How does the first oxidation step in peroxisomal beta-oxidation differ from mitochondrial beta-oxidation?

Answer 37

In peroxisomes, the first oxidation step produces hydrogen peroxide (H₂O₂) as FADH₂ is used to reduce molecular oxygen, unlike in mitochondria where FADH₂ enters the electron transport chain.

Question 38

What enzyme in peroxisomes converts hydrogen peroxide (H₂O₂) into water, and why is this important?

Answer 38

Catalase converts hydrogen peroxide into water, preventing the accumulation of potentially harmful H₂O₂.

Question 39

Why is less ATP generated in peroxisomal beta-oxidation compared to mitochondrial beta-oxidation?

Answer 39

Since electron carriers like FADH₂ do not feed into the electron transport chain in peroxisomes, fewer ATP molecules are produced.

Question 40

What role do unique auxiliary enzymes play in peroxisomal beta-oxidation?

Answer 40

These enzymes assist in processing specific types of fatty acids, such as very long-chain and branched-chain fatty acids, that are less efficiently oxidized in mitochondria.

Question 41

What happens to the glycerol released from triacylglycerol (TAG) hydrolysis by lipases?

Answer 41

Glycerol is transported to the liver, where it is metabolized into D-glyceraldehyde 3-phosphate and enters glycolysis or gluconeogenesis, depending on the body’s metabolic state.

Question 42

How is glycerol from fatty acid breakdown utilized for energy in the liver?

Answer 42

Liver-specific glycerol kinase converts glycerol into intermediates that enter glycolysis, eventually contributing to energy production or gluconeogenesis.

Question 43

Why does glycerol metabolism primarily occur in the liver?

Answer 43

Glycerol kinase, the enzyme required to metabolize glycerol, is only present in the liver, allowing it to be converted for energy or glucose production only in this organ.