Metabolic: lecture 21

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Questions and Answers

What is the primary role of α-ketoglutarate dehydrogenase in the citric acid cycle?

Converts succinate to fumarate

Regulates the synthesis of acetyl-CoA

Reacts with isocitrate to form α-ketoglutarate

Catalyzes the decarboxylation of α-ketoglutarate (correct)

Which molecules are produced in one turn of the citric acid cycle?

1 GTP and 3 FADH2

4 NADH and 1 FADH2

2 NADPH and 2 ATP

2 CO2 and 1 GTP (correct)

How does citrate undergo decarboxylation in the citric acid cycle?

By reacting symmetrically with aconitase

By losing the carboxyl group attached to the red carbon

By being converted directly to succinyl-CoA

Through an asymmetric reaction with aconitase (correct)

What is the fate of the 2 CO2 produced in one turn of the citric acid cycle?

They originate from the oxaloacetate used in the cycle Signup and view all the answers

What is the significance of FAD being covalently bound in succinate dehydrogenase?

It helps in the transfer of electrons during the electron transport chain Signup and view all the answers

What is the primary product generated during Stage 2 of respiration after the oxidation of Acetyl-CoA?

CO2 Signup and view all the answers

What role does oxaloacetate play in the reaction catalyzed by citrate synthase?

Forms a C-C bond with Acetyl-CoA Signup and view all the answers

Which statement accurately describes the role of aconitase in the citric acid cycle?

It adds water to citrate and removes it from isocitrate. Signup and view all the answers

Which of the following describes the conformation change in citrate synthase upon binding oxaloacetate?

It creates a binding site for acetyl-CoA. Signup and view all the answers

What type of regulation is exerted by succinyl-CoA on citrate synthase?

Allosteric inhibition Signup and view all the answers

What is the significance of the term 'moonlighting' with respect to cytosolic aconitase?

It refers to its role in regulating mRNA translation. Signup and view all the answers

What is the primary type of catalysis performed by aconitase?

Dehydration followed by hydration Signup and view all the answers

Which of the following statements correctly describes the impact of ATP on citrate synthase activity?

ATP inhibits the enzyme as part of feedback regulation. Signup and view all the answers

Study Notes

Respiration: Stage 2 - Acetyl-CoA Oxidation

Acetyl-CoA oxidation is the second stage of cellular respiration.
This stage generates more NADH, FADH₂, and one GTP.
Carbon atoms from carbohydrates, amino acids, and fatty acids are released during this stage.
The citric acid cycle is part of this stage.

Chemical Logic of the Citric Acid Cycle

Acetyl-CoA must be oxidized to CO₂ to extract the maximum potential energy (ATP).
Simple decarboxylation of Acetyl-CoA would yield CO₂ and methane (CH₄), which most organisms can't oxidize efficiently.
Methylene groups (-CH₂) are readily metabolized by an enzyme system found in most organisms.

The Citric Acid Cycle (CAC)

The Citric Acid Cycle (CAC) is a series of enzyme-catalyzed reactions.
The cycle starts with the molecule acetyl-CoA and ends at the molecule oxaloacetate.
The cycle involves a series of steps such as Claisen condensation, dehydrogenation, dehydration, hydration, dehydrogenation.
The process converts the acetyl-CoA into carbon dioxide, generating NADH, FADH₂, and GTP.

Standard Free Energy Changes of Citric Acid Cycle Reactions

The CAC is a series of reactions with different standard free energy changes.
Some reactions have negative free energy changes, meaning they are favorable/spontaneous.
Some reactions have positive free energy changes.
Physiological free energy changes are often considered in biological systems.

Regulation of the Citric Acid Cycle

Citrate synthase, isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase complex are regulated.
Feedback inhibition, where products of the cycle inhibit certain enzymes, regulates some reactions.
Other factors, like ATP and NADH, influence enzymatic activity.

Key Enzymes for Regulation of PDH and Citric Acid Cycle

Pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and 2-ketoglutarate dehydrogenase are crucial for controlling the citric cycle.
These enzymes are regulated by indicators like ATP, NADH, and succinyl-CoA, among other factors.
Feedback inhibition is a key regulatory mechanism.

C-C Bond Formation by Condensation of Acetyl-CoA and Oxaloacetate - Citrate Synthase

Citrate synthase catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate.
This step is crucial and highly thermodynamically favorable, driven by the release of CoA.
Activity depends on oxaloacetate concentration.
The reaction is regulated by substrate and product inhibition.

Induced Fit in Citrate Synthase

Binding of oxaloacetate induces a conformational change in the enzyme.
This change creates a binding site for acetyl-CoA, protecting the reactive carbanion in the transition state.

Citrate Synthase Regulation

Succinyl-CoA inhibits citrate synthase allosterically.
Other allosteric inhibitors include ATP, NADH, and product inhibition by citrate.
Succinyl-CoA's inhibition regulates the cycle, keeping acetyl-CoA levels in check.

Aconitase

Aconitase catalyzes the conversion of citrate to isocitrate.
It involves water removal from the citrate molecule and subsequent addition to cis-aconitate and finally to the isocitrate.
The iron-sulfur center in the enzyme is important in catalysis.
The conversion is necessary because citrate is a poor substrate for oxidation.

Cytosolic Aconitase moonlights as an Iron Response Protein

Cytosolic aconitase is a pivotal iron-response protein acting on mRNA translation.
Iron status regulates expression and translation, influencing levels of ferritin and the transferrin receptor.

Allosteric Regulation of Isocitrate Dehydrogenase (ICDH)

Isocitrate dehydrogenase (ICDH) is a crucial rate-limiting step in the citric acid cycle.
Allosteric activation occurs with an increase in ADP.
Allosteric inhibition is done with an increase in NADH and ATP.

Final Oxidative Decarboxylation - α-Ketoglutarate Dehydrogenase (αKGDH)

α-Ketoglutarate dehydrogenase complex catalyzes the oxidative decarboxylation of α-ketoglutarate to succinyl-CoA.
This reaction releases NADH and CO₂.
This complex has a structure and mechanism similar to pyruvate dehydrogenase.

Succinyl-CoA-Lipoyllysine

The reaction mechanism of α-ketoglutarate dehydrogenase is similar to pyruvate dehydrogenase.
Key components involve thiamine pyrophosphate (TPP), lipoyllysine, and FAD/FADH₂

Succinate Dehydrogenase

Succinate dehydrogenase is an enzyme in the citric acid cycle; it is part of the electron transport chain complex II.
It catalyzes the conversion of succinate to fumarate, while FAD acts as a coenzyme.
The enzyme is bound to the mitochondrial inner membrane.

Origin of C-Atoms in CO₂

The citric cycle begins with the acetyl group and produces carbon dioxide, but most carbon atoms are lost during the cycle.

Citrate is a symmetrical molecule, why is decarboxylation asymmetric?

Citrate reacts asymmetrically with aconitase.
Aconitase is stereospecific. only R-isocitrate is produced by aconitase.
Three point attachment to the active site dictates the reaction's outcome.

One Turn of the Citric Acid Cycle

The cycle oxidizes two carbons to CO₂ from the acetyl-CoA, which are not the same carbons during the cycle.
Energy is captured by electron transfer in the form of NADH and FADH₂.
It also produces 1 GTP, which can be converted to ATP.

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Description

This quiz focuses on the second stage of cellular respiration, specifically the oxidation of Acetyl-CoA. Learn about the generation of NADH, FADH₂, and GTP as well as the role of the citric acid cycle. Test your understanding of key processes and reactions involved in this critical metabolic stage.