Cellular Respiration: The Citric Acid Cycle, Oxidative Phosphorylation, and Fermentation

Stage 2: The Citric Acid Cycle

Overview of the Citric Acid Cycle

The citric acid cycle, also known as the Krebs cycle or TCA cycle, is a central metabolic pathway that completes the oxidation of organic molecules, yielding energy for the cell. It occurs in the mitochondrial matrix and is a key stage in cellular respiration.

• Acetyl CoA Formation: Pyruvate, produced from glycolysis, is oxidized to form acetyl CoA, CO2, and NADH.

• Cycle Inputs: Each turn of the cycle incorporates two carbons from acetyl CoA.

• Cycle Outputs: For each turn, 2 CO2 are released, 3 NADH and 1 FADH2 are produced, and 1 ATP (or GTP) is generated.

Key Equation:

$\text{Acetyl CoA} + 3\ NAD^+ + FAD + ADP + P_i \rightarrow 2\ CO_2 + 3\ NADH + 3\ H^+ + FADH_2 + ATP + CoA$

Example: In aerobic respiration, the citric acid cycle is repeated twice for each glucose molecule (since each glucose yields two pyruvate molecules).

Major Steps of the Citric Acid Cycle

The cycle consists of a series of enzyme-catalyzed reactions that systematically oxidize acetyl CoA, releasing energy and reducing equivalents.

• Step 1: Acetyl CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).

• Step 2: Citrate is rearranged and oxidized, releasing CO2 and generating NADH.

• Step 3: Alpha-ketoglutarate is formed and further oxidized, releasing another CO2 and producing NADH.

• Step 4: Succinyl-CoA is converted to succinate, generating ATP (or GTP).

• Step 5: Succinate is oxidized to fumarate, producing FADH2.

• Step 6: Fumarate is converted to malate, which is then oxidized to regenerate oxaloacetate, producing NADH.

Additional info: The cycle is amphibolic, serving both catabolic and anabolic functions in metabolism.

Stage 3: Oxidative Phosphorylation

Electron Transport Chain and ATP Production

Oxidative phosphorylation is the final stage of cellular respiration, where most ATP is produced. It occurs in the inner mitochondrial membrane and involves the electron transport chain (ETC) and chemiosmosis.

• Electron Transport: Electrons from NADH and FADH2 are transferred through a series of protein complexes to oxygen, the final electron acceptor, forming water.

• Proton Gradient: Energy from electron transfer pumps protons (H+) into the intermembrane space, creating an electrochemical gradient.

• ATP Synthesis: Protons flow back into the matrix through ATP synthase, driving the phosphorylation of ADP to ATP.

Key Equation:

$\text{NADH} + H^+ + 1/2\ O_2 \rightarrow \text{NAD}^+ + H_2O$

Example: Each NADH can generate approximately 2.5 ATP, and each FADH2 about 1.5 ATP.

Fermentation: Anaerobic Harvesting of Energy

Fermentation Pathways

Fermentation allows cells to produce ATP without oxygen by recycling NAD+ for glycolysis. It occurs in the cytosol and is used by muscle cells, yeasts, and certain bacteria under anaerobic conditions.

• Lactic Acid Fermentation: Pyruvate is reduced to lactate, regenerating NAD+.

• Alcohol Fermentation: Pyruvate is converted to ethanol and CO2, regenerating NAD+.

Key Equation (Lactic Acid):

$\text{Pyruvate} + NADH \rightarrow \text{Lactate} + NAD^+$

Key Equation (Alcohol):

$\text{Pyruvate} \rightarrow \text{Ethanol} + CO_2$

Example: Yeast cells use alcohol fermentation to produce ethanol in brewing and baking.

Additional info: Fermentation yields much less ATP per glucose than aerobic respiration.

Evolutionary Significance of Glycolysis

Ancient Origins of Glycolysis

Glycolysis is a universal metabolic pathway found in the cytosol of nearly all organisms. Its widespread presence suggests it evolved early in the history of life, likely in ancient prokaryotes before the atmosphere contained significant oxygen.

• Universality: Occurs in both prokaryotes and eukaryotes.

• Location: Takes place in the cytosol, independent of organelles.

• Oxygen Independence: Does not require oxygen, supporting its ancient origin.

Example: All living cells, from bacteria to humans, use glycolysis to break down glucose.

Connections Between Metabolic Pathways

Use of Organic Molecules as Fuel

Cells can utilize carbohydrates, fats, and proteins as sources of energy for cellular respiration. These molecules enter the metabolic pathways at different points.

• Carbohydrates: Broken down into sugars that enter glycolysis.

• Fats: Fatty acids are converted to acetyl CoA via beta-oxidation.

• Proteins: Amino acids are deaminated and enter the cycle as intermediates.

Additional info: The flexibility of metabolism allows survival on various diets, though carbohydrates are typically the primary energy source.

Organic Molecules for Biosynthesis

Intermediates from cellular respiration are used for the biosynthesis of other organic molecules, such as amino acids, nucleotides, and lipids. Metabolic pathways are regulated by feedback inhibition to maintain homeostasis.

• Anabolism: Synthesis of complex molecules from simpler ones using intermediates.

• Feedback Inhibition: End products inhibit enzymes earlier in the pathway to regulate production.

Example: Excess carbohydrates can be converted to fat and stored in adipose tissue, even on a low-fat diet.

Summary Table: Major Stages of Cellular Respiration

Stage	Main Location	Key Inputs	Key Outputs	ATP Yield
Glycolysis	Cytosol	Glucose, NAD+, ADP	Pyruvate, NADH, ATP	2
Citric Acid Cycle	Mitochondrial Matrix	Acetyl CoA, NAD+, FAD, ADP	CO2, NADH, FADH2, ATP	2
Oxidative Phosphorylation	Inner Mitochondrial Membrane	NADH, FADH2, O2, ADP	NAD+, FAD, H2O, ATP	~28
Fermentation	Cytosol	Glucose, NAD+, ADP	Lactate or Ethanol + CO2, NAD+, ATP	2