Pyruvate Oxidation and Citric Acid Cycle

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Questions and Answers

What is the product of the reductive carboxylation of pyruvate catalyzed by the malic enzyme?

Citrate

Oxaloacetate

Malate (correct)

Acetyl-CoA

Which domain is responsible for catalyzing Phase II of the biotin-dependent pyruvate carboxylase reaction?

Biotin carboxylation (BC) domain

Carboxyltransferase (CT) domain (correct)

Pyruvate carboxylation domain

Oxaloacetate synthesis domain

What is the role of the biotin-dependent pyruvate carboxylase reaction?

To convert malate to pyruvate

To convert acetyl-CoA to citrate

To convert citrate to isocitrate

To convert pyruvate to oxaloacetate (correct)

What is the purpose of the glyoxylate cycle?

To convert fat to carbohydrate Signup and view all the answers

How many molecules of acetyl-CoA enter the glyoxylate cycle?

Two Signup and view all the answers

What is the result of the reactions catalyzed by isocitrate lyase and malate synthase in the glyoxylate cycle?

The net synthesis of oxaloacetate Signup and view all the answers

What is the byproduct of the citric acid cycle that is bypassed in the glyoxylate cycle?

CO2 Signup and view all the answers

What is the function of the biotin-dependent pyruvate carboxylase reaction in the context of anaplerotic sequences?

To replace cycle intermediates Signup and view all the answers

What is the process catalyzed by the pyruvate dehydrogenase complex?

Oxidative decarboxylation Signup and view all the answers

How many enzymes are involved in pyruvate oxidation to acetyl-CoA?

Three Signup and view all the answers

What is the role of thiamine pyrophosphate (TPP) in pyruvate oxidation?

It is a co-factor for multiple enzymes Signup and view all the answers

What is the internal disulfide of 6,8-dithiooctanoic acid?

Lipoic acid Signup and view all the answers

How is lipoic acid joined to the pyruvate dehydrogenase complex?

Through an amide bond Signup and view all the answers

What is the outcome of pyruvate oxidation to acetyl-CoA?

Production of acetyl-CoA and CO2 Signup and view all the answers

What is the role of the pyruvate dehydrogenase complex in the citric acid cycle?

It is a major entry route for carbon into the citric acid cycle Signup and view all the answers

What is the derivative of thiamine (vitamin B1) that is involved in pyruvate oxidation?

Thiamine pyrophosphate (TPP) Signup and view all the answers

What is the function of the iron-sulfur cluster in the enzyme aconitase?

To coordinate the hydroxyl group and one of the carboxyl groups on the citrate molecule Signup and view all the answers

What is the product of the reaction catalyzed by isocitrate dehydrogenase?

α-Ketoglutarate Signup and view all the answers

What is the function of citrate binding at the base of large clefts in both catalytic domains of the homodimeric protein?

To induce a conformational change in the enzyme Signup and view all the answers

What is the name of the reactive species in the PDH complex?

Lipoyllysine Signup and view all the answers

What is the reason why tertiary alcohols cannot be oxidized without breaking a carbon-carbon bond?

Due to the chemical properties of the carbon-carbon bond Signup and view all the answers

What is the length of the lipoyllysine side chain?

14Å Signup and view all the answers

What is the result of the two-electron reduction of the cyclic disulfide of lipoamide?

Formation of the dithiol, dihydrolipoamide Signup and view all the answers

What is the intermediate formed during the isomerization reaction catalyzed by aconitase?

Cis-aconitate Signup and view all the answers

What is the role of lipoamide in pyruvate dehydrogenase?

Carrier of both electrons and acyl groups Signup and view all the answers

What is the product of the spontaneous decarboxylation of oxalosuccinate?

α-Ketoglutarate Signup and view all the answers

What is the role of aconitase in the Citric Acid Cycle?

To convert citrate to isocitrate Signup and view all the answers

What is the vitamin derivative required for coenzyme A synthesis?

Pantothenic acid Signup and view all the answers

Why are thioesters energy rich?

Due to lack of resonance stabilization Signup and view all the answers

What is the stereochemistry of the isocitrate produced by the isomerization reaction?

2R,3S Signup and view all the answers

What is the comparison of the free energies of hydrolysis of thioesters and oxygen esters?

Thioesters have a higher ΔG of hydrolysis Signup and view all the answers

What is the role of coenzyme A in pyruvate oxidation?

Activation of acyl groups Signup and view all the answers

What is the role of the permanent dipoles of the two -helices in the succinyl-CoA synthetase reaction?

To stabilize the phosphohistidine intermediate Signup and view all the answers

What is the structural analog of succinate that competitively inhibits succinate dehydrogenase?

Malonate Signup and view all the answers

Why is FAD a more suitable redox coenzyme for succinate dehydrogenase than NAD+?

FAD is a more powerful oxidant than NAD+ Signup and view all the answers

What is the outcome of the FAD-dependent dehydrogenation of succinate in the citric acid cycle?

Formation of a carbon-carbon double bond Signup and view all the answers

What is the function of fumarate hydratase in the citric acid cycle?

To catalyze the hydration of a carbon-carbon double bond Signup and view all the answers

What is the consequence of malonate inhibition of succinate dehydrogenase?

Inhibition of pyruvate oxidation Signup and view all the answers

What is the covalent binding partner of FAD in succinate dehydrogenase?

A specific histidine residue Signup and view all the answers

Why is a single C-C bond more difficult to oxidize than a C-O bond?

Because C-C bonds are stronger than C-O bonds Signup and view all the answers

Study Notes

Pyruvate Oxidation: A Major Entry Route for Carbon into the Citric Acid Cycle

Pyruvate oxidation to acetyl-CoA is catalyzed by the pyruvate dehydrogenase complex (PDH complex), which involves three enzymes and five coenzymes.
The PDH complex consists of multiple subunits, including E1, E2, and E3, with a complex structure that allows for the interaction of different subunits.

Coenzymes Involved in Pyruvate Oxidation and the Citric Acid Cycle

Thiamine pyrophosphate (TPP) is a coenzyme derived from vitamin B1, and it plays a critical role in oxidative energy metabolism and ATP production in the mitochondria.
TPP is a co-factor for multiple enzymes, including transketolase, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase.
Lipoic acid is a coenzyme that accepts the active aldehyde (hydroxyethyl group) generated by TPP, and it is joined to the PDH complex via an amide bond.
Lipoamide, or lipoyllysine, is the reactive species that can interact with the active sites of both the E1 and E3 components of the PDH complex.
Coenzyme A (CoA) participates in the activation of acyl groups, including the acetyl group derived from pyruvate.
Thioesters such as acetyl-CoA are energy-rich because they are destabilized relative to ordinary oxygen esters.

The Citric Acid Cycle

Step 2: Isomerization of citrate involves the conversion of citrate to isocitrate, a chiral secondary alcohol, which can be more readily oxidized.
Aconitase is the enzyme that catalyzes this reaction, which involves successive dehydration and hydration through cis-aconitate as a dehydrated intermediate.
The iron-sulfur cluster in aconitase coordinates the hydroxyl group and one of the carboxyl groups on the citrate molecule.
Step 3: Generation of CO2 by an NAD+-linked dehydrogenase involves the oxidation of isocitrate to oxalosuccinate, which spontaneously decarboxylates to give α-ketoglutarate.
Step 6: A flavin-dependent dehydrogenation involves the conversion of succinate to oxaloacetate, which is catalyzed by succinate dehydrogenase.
FAD is the redox coenzyme for succinate dehydrogenase, which is bound covalently to the enzyme protein through a specific histidine residue.
Step 7: Hydration of a carbon-carbon double bond involves the stereospecific trans hydration of the carbon-carbon double bond, which is catalyzed by fumarate hydratase.

Anaplerotic Sequences: The Need to Replace Cycle Intermediates

The biotin-dependent pyruvate carboxylase reaction involves the carboxylation of pyruvate to form oxaloacetate, which is necessary to replace cycle intermediates.
The reaction is catalyzed by the biotin carboxylation (BC) domain and the carboxyltransferase (CT) domain.
The glyoxylate cycle is an anabolic variant of the citric acid cycle that allows plants and bacteria to carry out net conversion of fat to carbohydrate, bypassing CO2-generating reactions.
The glyoxylate cycle involves the reactions catalyzed by isocitrate lyase and malate synthase, which bypass the three citric acid cycle steps between isocitrate and succinate, resulting in the net synthesis of oxaloacetate.

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Description

This quiz covers the process of pyruvate oxidation to acetyl-CoA, catalyzed by the pyruvate dehydrogenase complex, and its role in the citric acid cycle. It involves oxidative decarboxylation, enzymes, and coenzymes.