Lipid Catabolism - Biochemistry

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Question

Suppose that a fatty acid containing twelve carbons is broken down via beta oxidation. How many total molecules of ATP will be generated from this fatty acid?

Answer

To answer this question, we'll need to keep in mind some of the highlights of beta oxidation. When a fatty acid is broken down by this method, the hydrocarbon chain is broken down two carbons at a time through a series of repeating reactions. These two carbons come off in the form of acetyl-CoA, with an additional generation of one molecule each of NADH and . Since we know the original chain we're starting with contains twelve carbons, we know that there will be six molecules of acetyl-CoA produced. Furthermore, in order to generate these six molecules, beta-oxidation must proceed five times. Thus, we are going to have five molecules of NADH and five molecules of . The acetyl-CoA generated from beta oxidation is able to enter the citric acid cycle. For each molecule of acetyl-CoA that goes through the cycle, 1 molecule of ATP, 1 molecule of , and 3 molecules of NADH are generated. Therefore, since six molecules will be sent into the citric acid cycle, there will be a total generation of six molecules of ATP, six molecules of , and eighteen molecules of NADH. Now, we need to add everything up. So far, we have six molecules of ATP. We also have five molecules of NADH from beta-oxidation, and eighteen from the citric acid cycle, for a total of twenty-three. We've also obtained five molecules of from beta-oxidation, and another six from the citric acid cycle for a total of eleven. All of the NADH and that was generated from these reactions can donate their electrons into the electron transport chain to generate ATP. The rule of thumb is that for every NADH, molecules of ATP are produced. And for every molecules of , molecules of ATP is made. So, we have:

And if we add to this the six ATP that was generated directly by substrate-level phosphorylation in the citric acid cycle, that gives us a total of:

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Question

Consider the beta-oxidation of palmitate, a sixteen-carbon fatty acid chain.

If we look only at the formation of acetyl-CoA, how many acetyl-CoA are produced by the the oxidation of palmitate compared to the oxidation of glucose?

Answer

Palmitate is a sixteen-carbon chain and its beta-oxidation will produce 8 acetyl-CoA molecules, since each acetyl-CoA is two-carbons long. Glucose, on the other hand, will be broken down to form 2 acetyl-CoA molecules. Therefore, palmitate forms 4 times as many acetyl-CoA molecules.

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Question

What enzyme performs the shown step in beta oxidation?

Acyl coa dh reaction beta ox

Answer

This first step of beta oxidation is catalyzed by acyl-CoA dehydrogenase. One way to remember is that the enzyme is named for exactly what it does: remove a hydrogen (dehydrogenate) from acyl-CoA, which is the reactant. In order to be acetyl-CoA the R-group must specifically be a methyl group.

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Question

What enzyme performs the shown step in beta oxidation?

Enoyl coa hydratase rxn beta ox

Answer

This second step of beta oxidation is catalyzed by enoyl-CoA hydratase. One way to remember is that the enzyme is named for exactly what it does: adding water (hydrate) across the double bond of enoyl-CoA, which is the reactant.

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Question

What enzyme catalyses the shown step in beta oxidation?

L hydroxyacyl coa dh rxn beta ox

Answer

This third step in beta oxidation is catalyzed by L-hydroxacyl-CoA dehydrogenase. One way to remember is that the enzyme is named for exactly what it does: remove a hydrogen (dehydrogenate) L-hydroxyacyl-CoA (the reactant).

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Question

What enzyme catalyses the below step in beta oxidation?

Thiolase rxn beta oxidation

Answer

This fourth step in beta oxidation is catalyzed by thiolase. The reduced form of coenzyme-A is used as a cofactor to cleave the bond between the alpha and the beta carbon.

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Question

Which cofactor is required in the conversion of fatty acyl-CoA to trans enoyl-CoA by acyl-CoA dehydrogenase?

Answer

removes two hydrogens to form . These two electrons will be donated to the electron transport chain.

Acyl coa dh reaction beta ox

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Question

What reaction in beta oxidation does enoyl-CoA hydratase catalyze?

Answer

Enoyl-CoA hydratase catalyzes the the addition of water across the carbon-carbon double bond.

Enoyl coa hydratase rxn beta ox

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Question

Which reaction in beta oxidation does hydroxyacyl-CoA dehydrogenase catalyze?

Answer

Hydroxyacyl-CoA dehydrogenase oxidizes the beta hydroxyl group, forming a carbonyl.

L hydroxyacyl coa dh rxn beta ox

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Question

What reaction in beta oxidation does thiolase catalyze?

Answer

Thiolase catalyzes the cleavage of the beta-ketoacyl-CoA.

Thiolase rxn beta oxidation

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Question

What cofactor is required for the oxidation of beta-hydroxyacyl-CoA to beta-Ketoacyl-CoA by hydroxyacyl-CoA dehydrogenase?

Answer

NAD is required for the oxidation of beta-hydroxyacyl-CoA to beta-Ketoacyl-CoA by hydroxyacyl-CoA dehydrogenase.

L hydroxyacyl coa dh rxn beta ox

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Question

What are the two major products of the thiolase-catalyzed reaction?

Answer

The two major products of the thiolase-catalyzed reaction are acetyl-CoA and a fatty acyl-CoA shortened by two carbons.

Thiolase rxn beta oxidation

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Question

Before a fatty acid is able to undergo the beta-oxidation pathway, it must first be activated to form fatty acyl-CoA and transferred into the mitochondrial matrix from the cytoplasm of a cell via the activity of several enzymes.

What enzyme is responsible for synthesizing fatty acyl-CoA to be transported into the intermembrane space of a mitochondria?

Answer

Three enzymes are ultimately involved in activating fatty acids as fatty acyl-CoA and transferring this molecule into the inner mitochondrial matrix to be broken down via the beta-oxidation pathway. The first enzyme is acyl-CoA synthetase. This enzyme is a type of ATPase, and it uses the thermodynamically favorable dephosphorylation of ATP to drive the synthesis of fatty acyl-CoA from a fatty acid and CoASH. Fatty acids alone cannot cross mitochondrial membranes, but fatty acyl-CoA can cross the outer membrane.

Carnitine palmitoyl transferase II also synthesizes fatty acyl-CoA but acyl-CoA synthetase is the first enzyme to do so, and its dephosphorylation of ATP is what initially activates a fatty acid.

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Question

Fatty acyl-CoA enters the intermembrane space of a mitochondria via the enzyme acyl-CoA synthetase. Fatty acyl-CoA is the original input molecule of the beta-oxidation pathway, however, carnitine palmitoyl transferase I replaces the CoA with the molecule carnitine before being transported into the mitochondrial matrix.

Why does carnitine palmitoyl transferase replace coenzyme A with carnitine?

Answer

The carnitine transport protein, known as the carnitine-acylcarnitine translocase, allows the facilitated diffusion of a fatty acid into the mitochondrial matrix. Fatty acids cannot be transported into the mitochondrial matrix alone.

Following this step, carnitine palmitoyl transferase II catalyzes the reaction that reforms fatty acyl-CoA from CoASH and the fatty acylcarnitine.

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Question

What enzyme involved in the first step beta-oxidation pathway? What redox cofactor is formed?

Answer

Acyl-CoA dehydrogenase converts fatty acyl-CoA to trans-Δ2-enoyl-CoA forming the high energy redox cofactor from .

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Question

What enzyme is involved with the second step of the beta-oxidation pathway, and what input molecule other than trans-Δ2-enoyl-CoA is required?

Answer

Enoyl-CoA hydratase uses hydrates the double bond between the alpha and beta carbons of trans-Δ2-enoyl-CoA by adding a hydroxyl group to the beta carbon and a hydrogen to the alpha carbon.

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Question

What is the enzyme involved with the third step of the beta-oxidation pathway? What redox cofactors are formed?

Answer

3-L-hydroxyacyl-CoA dehydrogenase converts 3-L-Hydroxyacyl-CoA to beta-Ketoacyl-CoA, forming the high energy redox cofactor from . This reaction oxidizes the hydroxyl group on the beta carbon of 3-L-hydroxyacyl-CoA to a carbonyl group, and adds a hydrogen with 2 high energy electrons to .

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Question

What enzyme catalyzes the fourth reaction in the beta-oxidation pathway? What cofactor is needed for the reaction to occur?

Answer

Beta-Ketoacyl-CoA thiolase converts beta-Ketoacyl-CoA back to acetyl-CoA and a fatty acyl-CoA two carbons shorter than the original fatty acyl-CoA. The new cofactor of acyl-CoA bonds to the beta carbon of beta-Ketoacyl-CoA, and thus the beta carbon of beta-Ketoacyl-CoA becomes the new alpha carbon of the new fatty acyl-CoA. The new fatty acyl-CoA can then re-enter into beta oxidation pathway.

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Question

The beta oxidation pathway can be described as __________.

Answer

The beta-oxidation pathway is cyclic. Two carbons are removed from a fatty acid chain each time it goes around the pathway. If the initial fatty acid chain has an even number of carbons then the final round of beta oxidation yields two copies of acetyl-CoA.

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Question

What is the final product in the beta oxidation of fatty acids with an odd number of carbons?

Answer

In the last round of beta oxidation, fatty acids with odd numbers of carbons will yield acetyl-CoA and Coenzyme-A attached to a fatty acid with three carbons (propionyl-CoA)

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