One Turn Of The Citric Acid Cycle Produces

One Turn of the Citric Acid Cycle Produces: A Deep Dive into the Krebs Cycle

The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a central metabolic pathway in all aerobic organisms. It's a crucial link between glycolysis and oxidative phosphorylation, playing a vital role in energy production and biosynthesis. Understanding what a single turn of this cycle produces is fundamental to grasping cellular respiration's overall efficiency.

The Key Players: Inputs and Outputs of the Citric Acid Cycle

Before delving into the specifics of what one turn generates, let's establish the essential components:

Inputs:

• Acetyl-CoA (Acetyl Coenzyme A): This two-carbon molecule, derived from the breakdown of carbohydrates, fats, and proteins, is the primary fuel for the citric acid cycle. It enters the cycle by combining with oxaloacetate.
• Oxaloacetate: A four-carbon molecule that acts as a crucial starting point and is regenerated at the end of each cycle, ensuring its continuous operation.
• NAD+ (Nicotinamide adenine dinucleotide): A coenzyme that acts as an electron acceptor, crucial for generating NADH.
• FAD (Flavin adenine dinucleotide): Another coenzyme that accepts electrons, leading to the production of FADH2.
• Water (H₂O): Required in several steps of the cycle.

Outputs:

The citric acid cycle doesn't simply burn fuel; it generates a range of essential molecules:

• ATP (Adenosine triphosphate): Directly, only one molecule of ATP (or GTP in some organisms) is produced per cycle.
• NADH: Three molecules of NADH are produced per cycle. These are high-energy electron carriers crucial for oxidative phosphorylation.
• FADH2: One molecule of FADH2 is generated per cycle. Similar to NADH, it's a high-energy electron carrier used in oxidative phosphorylation.
• CO₂ (Carbon dioxide): Two molecules of carbon dioxide are released per cycle as waste products. This represents the oxidation of the acetyl group.
• Oxaloacetate: The cycle regenerates oxaloacetate, ensuring its continuation.

A Detailed Look at the Eight Steps: What Happens in Each Turn

The citric acid cycle is a cyclical series of eight enzyme-catalyzed reactions, each contributing to the overall output. Let's examine each step, focusing on how they contribute to the net yield of one cycle:

1. Citrate Synthase: Acetyl-CoA combines with oxaloacetate to form citrate (a six-carbon molecule). This step is highly exergonic (releases energy), driving the reaction forward. No ATP, NADH, or FADH2 is produced here.

2. Aconitase: Citrate is isomerized to isocitrate (another six-carbon molecule). This isomerization is necessary for the next step's oxidation. No ATP, NADH, or FADH2 is produced here. This step is crucial for the subsequent oxidation.

3. Isocitrate Dehydrogenase: Isocitrate undergoes oxidative decarboxylation, meaning it loses a carbon atom as CO₂ and an electron pair is transferred to NAD+, forming NADH. This is the first step where one NADH molecule is produced per cycle. This reaction is highly exergonic and a key regulatory point of the citric acid cycle.

4. α-Ketoglutarate Dehydrogenase: α-ketoglutarate (a five-carbon molecule) undergoes oxidative decarboxylation, similar to step 3. This releases another CO₂ molecule and generates one NADH. This step is also highly regulated and is a significant source of NADH for the electron transport chain.

5. Succinyl-CoA Synthetase: Succinyl-CoA (a four-carbon molecule) is converted to succinate (also a four-carbon molecule). This step involves substrate-level phosphorylation, which means the energy released from the reaction is directly used to generate one GTP (or ATP) molecule. This is the only step where ATP (or GTP) is produced directly within the citric acid cycle.

6. Succinate Dehydrogenase: Succinate is oxidized to fumarate (another four-carbon molecule), and the electrons are transferred to FAD, forming one FADH2. This is a unique step because succinate dehydrogenase is embedded in the inner mitochondrial membrane, directly interacting with the electron transport chain.

7. Fumarase: Fumarate is hydrated (water is added) to form malate (a four-carbon molecule). No ATP, NADH, or FADH2 is produced. This hydration step prepares the molecule for the final oxidation.

8. Malate Dehydrogenase: Malate is oxidized to oxaloacetate, regenerating the starting molecule and generating one NADH. This completes the cycle, allowing the process to begin anew with another Acetyl-CoA molecule.

The Big Picture: Total Yield per Cycle and its Significance

Summarizing the output from one turn of the citric acid cycle:

• ATP (or GTP): 1
• NADH: 3
• FADH2: 1
• CO2: 2

While the direct ATP yield is modest, the crucial contribution lies in the production of NADH and FADH2. These electron carriers are essential for oxidative phosphorylation, the final stage of cellular respiration. In oxidative phosphorylation, the electrons from NADH and FADH2 are passed along an electron transport chain, ultimately driving the synthesis of a substantial amount of ATP through chemiosmosis.

It's estimated that each NADH molecule yields approximately 2.5 ATP, and each FADH2 molecule yields approximately 1.5 ATP in oxidative phosphorylation. Therefore, the total ATP yield indirectly derived from one turn of the citric acid cycle is approximately: (3 NADH x 2.5 ATP/NADH) + (1 FADH2 x 1.5 ATP/FADH2) = 7.5 + 1.5 = 9 ATP.

Adding the one ATP (or GTP) directly produced in the cycle, the total theoretical ATP yield per acetyl-CoA molecule entering the citric acid cycle is approximately 10 ATP. This highlights the cycle's critical role in maximizing energy extraction from the initial breakdown of glucose and other fuel molecules.

Regulation of the Citric Acid Cycle: A Fine-Tuned Process

The citric acid cycle's activity is tightly regulated to meet the cell's energy demands. Several factors influence its rate:

• Substrate Availability: The concentrations of Acetyl-CoA and oxaloacetate directly influence the cycle's rate. Low levels of either will limit the cycle's activity.
• Energy Charge: The ratio of ATP to ADP and AMP acts as a feedback mechanism. High ATP levels inhibit several enzymes in the cycle, slowing down ATP production.
• Inhibition by NADH and FADH2: High levels of NADH and FADH2, the reduced coenzymes, inhibit several enzymes, preventing overproduction of these reducing agents.
• Allosteric Regulation: Specific enzymes are subject to allosteric regulation, meaning molecules bind to them at sites other than the active site, modifying their activity. For example, citrate inhibits phosphofructokinase, an enzyme in glycolysis, preventing excessive glucose breakdown if the citric acid cycle is already saturated.

Beyond Energy Production: Anabolic Roles of the Citric Acid Cycle

The citric acid cycle is not solely a catabolic pathway (breaking down molecules for energy). It's also an amphoteric pathway; it plays crucial anabolic roles, providing intermediates for the synthesis of various biomolecules, including:

• Amino Acids: Several citric acid cycle intermediates serve as precursors for the synthesis of amino acids, contributing to protein synthesis.
• Fatty Acids: Citrate can be transported out of the mitochondria and used for fatty acid biosynthesis in the cytoplasm.
• Glucose: In gluconeogenesis (glucose synthesis), certain intermediates can be used to build glucose molecules.
• Heme: Succinyl-CoA is a precursor for heme biosynthesis.
• Porphyrins: Other intermediates contribute to the biosynthesis of porphyrins, essential components of various molecules like hemoglobin and cytochromes.

Conclusion: The Citric Acid Cycle – A Metabolic Hub

The citric acid cycle is more than just a series of chemical reactions; it's a central metabolic hub, playing a critical role in energy production, biosynthesis, and cellular regulation. Understanding the output of a single turn – one ATP, three NADH, one FADH2, and two CO2 – is crucial for appreciating its contribution to cellular respiration and overall cellular metabolism. The intricate regulation and the cycle's diverse roles underscore its fundamental importance in maintaining cellular life. The indirect ATP yield, far exceeding the direct yield, truly highlights its essential function in providing the energy needed for numerous cellular processes. Its connection to biosynthesis further emphasizes its critical role as a central metabolic hub in all aerobic organisms.