The Citric Acid Cycle: Videos & Practice Problems

The Citric Acid Cycle, also known as the Krebs Cycle, is a crucial metabolic pathway consisting of eight biochemical reactions that play a vital role in cellular respiration. In the first phase, known as citrate formation, the cycle begins with the interaction of two key molecules: oxaloacetate and acetyl CoA. Oxaloacetate, which is regenerated in a later phase of the cycle, combines with acetyl CoA to produce citrate.

This initial reaction is significant as it marks the entry of acetyl CoA into the cycle, facilitating the conversion of energy stored in carbohydrates, fats, and proteins into usable forms. The formation of citrate is essential for the continuation of the cycle, as it sets the stage for subsequent reactions that will ultimately lead to the production of ATP, the energy currency of the cell.

In summary, the first step of the Citric Acid Cycle involves the condensation of oxaloacetate and acetyl CoA to form citrate, highlighting the interconnectedness of metabolic pathways and the importance of this cycle in energy production.

The citric acid cycle, also known as the Krebs cycle, begins with the formation of citrate, which is a crucial step in cellular respiration. In this initial reaction, an acetyl group from acetyl CoA combines with oxaloacetate, specifically at carbon 2, to produce citrate, the second metabolite in the cycle.

The mechanism starts with a basic residue that deprotonates the alpha hydrogen of oxaloacetate. This deprotonation leads to the breaking of a bond, allowing carbon to retain the electrons and form a double bond, resulting in the creation of an enolate. This process is known as enolization, which is essential for the subsequent steps.

Next, the enolate formed from acetyl CoA reacts with the acetyl CoA molecule. The oxygen from the enolate donates its lone pair to form a pi bond with the carbon, causing the existing pi bond to break. This reaction is crucial as it prevents the carbon from exceeding its tetravalent state, leading to the formation of a hydroxyl group through the addition of a proton (H⁺).

At this stage, an intermediate is formed through what is referred to as aldol addition. The final step involves thioester hydrolysis, where the bond between the sulfur in CoA and the acetyl group is cleaved. This reaction results in the formation of a carboxylate group, ultimately yielding citrate.

In summary, the mechanism of citrate formation in the citric acid cycle involves a series of well-coordinated steps, including enolization, aldol addition, and thioester hydrolysis, leading to the production of citrate, which plays a vital role in energy production within the cell.

In the process of converting oxaloacetate to citrate, two carbon atoms are added. This occurs during the hydrolysis of Acetyl CoA, where the acetyl group, which consists of two carbon atoms, combines with oxaloacetate. The resulting compound, citrate, is formed as a key intermediate in the citric acid cycle (Krebs cycle), which is essential for cellular respiration and energy production.

To summarize, the addition of the two carbon atoms from Acetyl CoA to oxaloacetate is crucial for the synthesis of citrate, highlighting the importance of this reaction in metabolic pathways.

Phase B of the Citric Acid Cycle focuses on the formation of succinyl CoA and includes three key reactions: the conversion of citrate to isocitrate, isocitrate to alpha-ketoglutarate, and alpha-ketoglutarate to succinyl CoA. In the first reaction, citrate is transformed into isocitrate, setting the stage for subsequent transformations.

In the second reaction, isocitrate undergoes oxidative decarboxylation to form alpha-ketoglutarate. This process is significant as it produces one molecule of NADH, an essential electron carrier, and releases carbon dioxide (CO₂). The generation of NADH is crucial for cellular respiration, as it plays a vital role in the electron transport chain, facilitating ATP production.

The third reaction involves the conversion of alpha-ketoglutarate to succinyl CoA, which also results in the release of another molecule of NADH and CO₂. This step is similarly important for energy production, as succinyl CoA is a key intermediate that can enter various metabolic pathways.

Overall, Phase B of the Citric Acid Cycle is characterized by the production of two moles of NADH and two moles of CO₂, with each reaction contributing to the cycle's efficiency in energy extraction from organic molecules. Understanding these transformations is essential for grasping how the cycle contributes to cellular metabolism and energy production.

In the citric acid cycle, the second reaction involves the isomerization of citrate, a tertiary alcohol, to isocitrate, a secondary alcohol. This transformation is crucial because tertiary alcohols cannot undergo oxidation, while secondary alcohols can. The process begins with a basic residue that deprotonates a hydrogen atom from the tertiary alcohol. As a result, a carbon-carbon bond breaks, leading to the formation of a double bond.

During this reaction, a hydroxide ion (OH^-) is released, which then combines with a proton (H⁺) to facilitate the reaction. This mechanism can be described as an E2 dehydration, where a pi bond is formed, resulting in an intermediate structure. The reaction follows the principles of anti-Markovnikov hydration, where the hydroxyl group (OH) attaches to one carbon, while a hydrogen atom (H) attaches to the adjacent carbon. This specific arrangement is essential for the conversion from citrate to isocitrate, highlighting the importance of understanding reaction mechanisms in metabolic pathways.

In the citric acid cycle, the third reaction involves the oxidation of a secondary alcohol and decarboxylation, which is a crucial step in cellular respiration. This process begins with isocitrate, where the secondary alcohol undergoes oxidation facilitated by the coenzyme NAD⁺. During this reaction, one molecule of NAD⁺ is reduced to NADH, and a carbon atom is released as carbon dioxide (CO₂), highlighting the significance of decarboxylation in the cycle.

The reaction can be summarized as follows: the secondary alcohol in isocitrate is oxidized, resulting in the formation of an oxidized intermediate. A magnesium ion plays a vital role in stabilizing the negative charges that arise during this process. As the negatively charged oxygen forms a double bond with the carbon, it breaks a bond to maintain the tetravalent nature of carbon, ensuring it does not exceed four bonds.

This transformation leads to the creation of an enolate intermediate. Through a process known as tautomerization, the enolate can convert into alpha-ketoglutarate. In this step, the negatively charged oxygen forms another pi bond, which facilitates the transfer of a hydrogen ion (H⁺), resulting in the carbon gaining two hydrogen atoms and forming a carbonyl group. This mechanism illustrates the intricate biochemical transformations that occur in the citric acid cycle, emphasizing the importance of oxidation and decarboxylation in energy production.

The reaction described involves a crucial mechanism within the citric acid cycle, specifically highlighting an oxidation and decarboxylation process. This step is the second decarboxylation in the cycle, where a carbon atom is removed, resulting in the release of carbon dioxide (CO₂). The reaction can be summarized as a C₁ oxidation coupled with decarboxylation.

During this process, the coenzyme NAD⁺ is reduced to NADH, indicating a transfer of electrons. The substrate involved in this transformation is alpha-ketoglutarate, which is converted to succinyl CoA. This conversion is characterized by the addition of a more electronegative sulfur atom to Carbon 1 of the substrate, which signifies the oxidation step. The overall reaction can be represented as follows:

\[\text{alpha-ketoglutarate} + \text{NAD}^+ + \text{CoA} \rightarrow \text{succinyl CoA} + \text{NADH} + \text{CO}_2\]

In summary, this reaction not only illustrates the importance of oxidation in metabolic pathways but also emphasizes the role of decarboxylation in the citric acid cycle, contributing to the overall energy production in cellular respiration.

The Citric Acid Cycle, also known as the Krebs Cycle, is a crucial metabolic pathway that plays a significant role in cellular respiration. It consists of a series of enzymatic reactions that convert acetyl CoA into energy-rich molecules. Understanding the specific reactions within this cycle is essential for grasping how energy is produced in aerobic organisms.

One of the key steps in the cycle is the oxidation of alpha-ketoglutarate to succinyl CoA, which occurs in reaction 4 of phase B. This reaction is vital as it not only facilitates the conversion of one molecule to another but also contributes to the overall energy yield of the cycle.

Another important reaction is the conversion of oxaloacetate to citrate, which takes place in reaction 1 of phase A. In this step, oxaloacetate combines with acetyl CoA to form citrate, marking the beginning of the cycle and setting the stage for subsequent reactions.

Additionally, the enzyme isocitrate dehydrogenase catalyzes the oxidation of isocitrate to alpha-ketoglutarate in reaction 3 of phase B. This step is crucial for the decarboxylation process, which releases carbon dioxide and generates NADH, an important electron carrier.

Lastly, the isomerization of citrate to isocitrate occurs in reaction 2 of phase B. This reaction involves the conversion of a tertiary alcohol in citrate to a secondary alcohol in isocitrate, preparing the molecule for further oxidation. This transformation is essential for the efficient progression of the cycle and the eventual production of ATP.

Overall, each of these reactions plays a significant role in the Citric Acid Cycle, contributing to the metabolic processes that generate energy for the cell.

Phase C of the citric acid cycle, which encompasses reactions 5 to 8, culminates in the regeneration of oxaloacetate. This phase begins with the conversion of succinyl CoA into succinate in reaction 5, where the CoA group is released. In reaction 6, succinate undergoes oxidation facilitated by FAD, transforming it into fumarate, a flat molecule. Following this, reaction 7 involves the hydration of fumarate to form malate, introducing an alcohol functional group. Finally, in reaction 8, malate is oxidized by NAD⁺ to regenerate oxaloacetate, completing the cycle. It is important to note that the citric acid cycle can undergo two complete runs, allowing for continuous energy production.

In the context of nucleophilic acyl substitution reactions, specifically reaction 5, we observe the transformation involving succinyl CoA. This reaction initiates with a basic residue that deprotonates a hydrogen atom, facilitating the breaking of a bond and allowing the electrons to shift towards the oxygen atom. Concurrently, a negatively charged oxygen atom attacks the carbonyl carbon, leading to the cleavage of the pi bond, which subsequently shifts to the oxygen, characteristic of carboxylic acid derivatives that undergo substitution rather than addition.

As the reaction progresses, the lone pair on the oxygen reforms the pi bond, resulting in the release of the succinyl CoA group. This transformation yields a structure where a phosphate group is now attached to the carbonyl carbon. The phosphate group can then engage in a nucleophilic attack on the phosphorus atom, prompting the pi bond to shift to the oxygen. In this step, the oxygen reforms its double bond, causing another bond to break and revert to the oxygen, ultimately leading to the formation of succinate.

This process not only regenerates the dicarboxyl group but also incorporates an additional phosphate group into the structure, culminating in the production of ATP. The formation of ATP, a high-energy molecule, signifies the generation of energy during this reaction, highlighting the importance of nucleophilic acyl substitution in metabolic pathways.

In the context of the citric acid cycle, reaction 6 involves a dehydrogenation process where hydrogen atoms are removed from succinate, converting it into fumarate. This specific reaction is characterized as a C₂ to C₃ dehydrogenation, facilitated by the coenzyme FAD (flavin adenine dinucleotide). During this transformation, one molecule of FAD is reduced to FADH₂.

The mechanism begins with a basic residue that deprotonates succinate, leading to the removal of a hydrogen atom. This removal results in the formation of a double bond (π bond) between the carbon atoms, while a hydride ion (H^-) is transferred to FAD, thus reducing it to FADH₂. Consequently, the reaction not only oxidizes succinate but also generates fumarate, illustrating how FAD acts as an oxidizing agent in this process.

Overall, this reaction exemplifies the role of FAD in converting single bonds to double bonds, highlighting its importance in the citric acid cycle and energy metabolism.

The citric acid cycle, also known as the Krebs cycle, is a crucial metabolic pathway that plays a significant role in cellular respiration. It involves a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.

In the cycle, reaction 5 is particularly important as it converts succinyl-CoA to succinate. This conversion occurs through hydrolysis, releasing energy that is harnessed to produce ATP, a high-energy molecule essential for various cellular processes. The statement regarding this reaction is accurate.

Following this, reaction 6 involves the oxidation of succinate to fumarate, facilitated by the coenzyme FAD. This step is also true, as it highlights the cycle's role in energy production through oxidation reactions.

However, a common misconception arises with the assertion that phase C of the citric acid cycle does not contain any oxidation reactions. This statement is incorrect. In fact, phase C includes several oxidation reactions where NAD⁺ and FAD are utilized to oxidize substrates, contributing to the overall energy yield of the cycle.

Lastly, the hydrolysis of succinyl-CoA to succinate indeed creates a high-energy molecule, confirming the accuracy of this statement as well. Therefore, the only incorrect statement among the options provided is that phase C lacks oxidation reactions.

In the context of the citric acid cycle, hydration plays a crucial role in the conversion of fumarate to malate through a specific mechanism known as conjugate addition. This reaction involves the addition of water to the double bond of fumarate, which is a key step in the cycle.

During this process, a basic residue facilitates the deprotonation of water, allowing it to act as a nucleophile. The hydroxide ion generated from this reaction attacks one of the carbon atoms in the fumarate, leading to the breaking of a pi bond. This results in the formation of a negatively charged oxygen atom, which is now bonded to the carbon skeleton.

The newly formed negatively charged oxygen can undergo resonance, allowing its lone pair to form a pi bond with another carbon atom, while simultaneously breaking a pi bond with the adjacent carbon. This resonance stabilizes the intermediate structure and prepares it for the final steps of the reaction.

Ultimately, a proton (H⁺) is added to the negatively charged oxygen, resulting in the formation of malate. This transformation highlights the importance of conjugate addition reactions in biochemical pathways, illustrating how water can be utilized to modify organic compounds effectively.

In the context of the citric acid cycle, Reaction 8 illustrates an important oxidation process where malate is converted to oxaloacetate. This reaction involves the coenzyme NAD⁺, which plays a crucial role in the oxidation by accepting electrons. During this transformation, one molecule of NAD⁺ is reduced to NADH.

The mechanism begins with a basic residue that facilitates the deprotonation of malate. This process involves the removal of a hydrogen atom (H), leading to the breaking of a bond and the formation of a π bond. The hydrogen atom is released as a hydride ion (H^-), which then combines with NAD⁺ to form NADH. This step is essential as it highlights the electron transfer that characterizes oxidation reactions.

Overall, this reaction is a key component of the citric acid cycle, showcasing how malate is oxidized to oxaloacetate while simultaneously reducing NAD⁺ to NADH, thus contributing to the cycle's energy production and metabolic processes.

The citric acid cycle, also known as the Krebs cycle, is a crucial metabolic pathway that plays a significant role in cellular respiration. It involves a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. Understanding the core steps of this cycle is essential for grasping how energy is produced in cells.

One of the key reactions in the citric acid cycle is the oxidation of malate to oxaloacetate, which occurs in reaction 8. This step is vital as oxaloacetate is the first metabolite encountered in the cycle and is regenerated at the end, allowing the cycle to continue. The conversion of succinate to fumarate, which involves the loss of two hydrogen atoms, takes place in reaction 6. This step is important for the overall energy yield of the cycle.

Another significant reaction is the hydrolysis of Succinyl CoA to produce succinate, occurring in reaction 5. This reaction is crucial as it releases energy that is harnessed in subsequent steps. Additionally, the hydration of fumarate to form malate is represented in reaction 7, completing the transformation from fumarate back to malate, which is essential for the cycle's continuity.

In summary, the core steps identified in the citric acid cycle based on the provided descriptions are as follows: the oxidation of malate to oxaloacetate (reaction 8), the conversion of succinate to fumarate (reaction 6), the hydrolysis of Succinyl CoA to succinate (reaction 5), and the hydration of fumarate to malate (reaction 7). These reactions illustrate the intricate processes that contribute to the cycle's function in energy production.

The citric acid cycle, also known as the Krebs cycle, is a crucial metabolic pathway that plays a significant role in cellular respiration. To effectively remember the mechanisms involved in each of the eight reactions of this cycle, a mnemonic can be employed: "Never Ignore Ordinary Habits, Daily Habits, Outperform." This phrase corresponds to the specific types of reactions that occur at each step.

In the first reaction, oxaloacetate is converted to citrate through a process known as nucleophilic addition, represented by "Never" (N). The second reaction involves the isomerization of citrate to isocitrate, which is captured by "Ignore." The third reaction transitions isocitrate to alpha-ketoglutarate, characterized by oxidation and decarboxylation, denoted by "Ordinary." This is the first decarboxylation step in the cycle.

Continuing with the fourth reaction, alpha-ketoglutarate is converted to succinyl CoA, which also involves oxidation and decarboxylation, reinforcing the "Ordinary" mechanism. The fifth reaction, where succinyl CoA is hydrolyzed to succinate, is represented by "Habits." In the sixth reaction, succinate undergoes dehydration to form fumarate, captured by "Daily." The seventh reaction involves the hydration of fumarate to malate, represented by "Habits" again.

Finally, the cycle concludes with the oxidation of malate back to oxaloacetate, encapsulated by "Outperform." This mnemonic serves as a valuable tool for recalling the mechanisms of the citric acid cycle, highlighting the importance of each reaction step in the overall metabolic process.

Electrophilic addition reactions are characteristic of molecules containing pi bonds, such as alkenes and alkynes. In the context of the citric acid cycle, fumarate is a notable example of a flat molecule due to the presence of pi bonds between its internal carbon atoms. The conversion of fumarate to malate involves a hydration reaction, where water is added to the alkene, transforming it into an alcohol. This process exemplifies an electrophilic addition reaction.

To identify the specific reaction step, we note that fumarate is produced in reaction 6, where succinate is oxidized to fumarate. The subsequent step, reaction 7, involves the hydration of fumarate to form malate. Therefore, the correct classification of the electrophilic addition reaction occurs in reaction 7, where fumarate is hydrated to malate using water. This highlights the significance of electrophilic addition in biochemical pathways, particularly in the transformation of metabolites within the citric acid cycle.

The Citric Acid Cycle, also known as the Krebs Cycle, plays a crucial role in cellular respiration by degrading acetyl groups to produce carbon dioxide and high-energy molecules, specifically NADH, FADH₂, and ATP. This cycle consists of three distinct phases: A, B, and C, which can be remembered using various mnemonic devices.

One effective memory tool is to visualize the Krebs Cycle as a "big crab," which helps recall the three phases. Another mnemonic involves imagining "4 owls and 1 sea hawk in a circus ring." In this analogy, the "4 owls" represent the four oxidation reactions that occur within the cycle, yielding NADH and FADH₂. These oxidation reactions are distributed between phases B and C, with two occurring in each phase. The "1 sea hawk" signifies the single hydrolysis reaction in phase C, which is responsible for producing ATP.

The cyclic nature of the Citric Acid Cycle is emphasized by the imagery of a circus ring, reinforcing the idea that the cycle continuously processes acetyl groups. In summary, the Citric Acid Cycle features four oxidation reactions (two in phase B and two in phase C) that generate NADH and FADH₂, while the hydrolysis reaction in phase C produces ATP. Understanding these components is essential for grasping the overall function and significance of the Krebs Cycle in energy metabolism.

The citric acid cycle, also known as the Krebs cycle, is a crucial metabolic pathway that processes Acetyl CoA derived from glucose. Each glucose molecule yields two Acetyl CoA, which enter the cycle. The cycle can be divided into phases, with specific reactions contributing to the production of high-energy molecules.

In phase B of the cycle, reactions 3 and 4 are responsible for generating NADH. Each of these reactions produces one NADH, and since the cycle runs twice for each glucose molecule, this results in a total of 4 NADH produced (2 from each reaction). Moving to phase C, which encompasses reactions 5 to 8, the cycle produces ATP and FADH₂. Each complete turn of the cycle generates 1 ATP, leading to a total of 2 ATP from two turns. Additionally, reaction 6 produces 1 FADH₂ per turn, resulting in 2 FADH₂ from two cycles.

Furthermore, reaction 8 involves the oxidation of malate to oxaloacetate, producing another 2 NADH from two turns of the cycle. When summarizing the total output from the citric acid cycle, starting with 2 Acetyl CoA, we find that the cycle produces:

• 2 ATP
• 2 FADH₂
• 6 NADH

Thus, the overall yield of high-energy molecules from the citric acid cycle is essential for cellular respiration, as these molecules play a significant role in the electron transport chain, ultimately leading to ATP synthesis. The key molecule that initiates the cycle is oxaloacetate, which combines with Acetyl CoA to begin the process anew.

To effectively recall the high-energy molecules generated during the citric acid cycle, a mnemonic can be utilized: "Under trees in a forest, there lived 5 ants and 6 flies." This phrase helps associate specific molecules with their corresponding reactions.

In this mnemonic, "N D" translates to NADH, which is produced in reactions 3, 4, and 8 of the cycle. The "trees in a forest" signifies the production of NADH in these specific reactions. Next, the letter "A" represents ATP, which is generated in reaction 5. This reaction involves the hydrolysis of succinyl CoA to succinate, marking a key step in energy production.

Finally, "F" for "flies" stands for FADH₂, produced in reaction 6, where succinate is converted to fumarate. Thus, the three high-energy molecules to remember are NADH, ATP, and FADH₂, along with their respective reactions: reactions 3, 4, and 8 for NADH; reaction 5 for ATP; and reaction 6 for FADH₂.

The citric acid cycle, also known as the Krebs cycle, is a crucial metabolic pathway that generates high-energy molecules essential for cellular respiration. In this cycle, specific reactions produce key high-energy molecules: NADH, FADH₂, and ATP. To identify how many reactions contribute to these high-energy products, we can use a mnemonic device: "under threes in a forest, 48, there lived 5 ants, and 6 flies."

In this context, the numbers correspond to specific steps in the cycle. The production of NADH occurs in steps 3, 4, and 8. This is represented by the phrase "there lived 5 ants," where the number 5 indicates the production of ATP in step 5. This ATP is generated through substrate-level phosphorylation, utilizing GTP to convert ADP into ATP. The "6 flies" refer to FADH₂, which is produced in step 6.

Summarizing these findings, the reactions that yield high-energy molecules in the citric acid cycle are as follows: NADH is produced in steps 3, 4, and 8; ATP is produced in step 5; and FADH₂ is produced in step 6. Therefore, a total of five reactions within the citric acid cycle are responsible for generating these high-energy molecules, highlighting the cycle's importance in energy metabolism.