Cellular Respiration and Fermentation: Chapter 9 Study Notes

Cellular Respiration and Fermentation

Overview and Roadmap

Cellular respiration and fermentation are essential metabolic pathways that allow cells to produce ATP from sugars and other high-energy compounds. This chapter explores how cells generate ATP both in the presence and absence of oxygen, focusing on glycolysis, pyruvate oxidation, the citric acid cycle, electron transport and chemiosmosis, and fermentation.

Introduction to Cellular Energy Production

Life requires energy, and ATP is the primary molecule that fuels cellular work. Metabolic pathways harvest energy from high-energy molecules, such as glucose, and use it to add a phosphate group to ADP, forming ATP. Cells generally contain enough ATP for only a short period and must continually produce it.

• ATP: Adenosine triphosphate, the energy currency of the cell.

• Glucose: A key substrate for ATP production, obtained from photosynthesis (plants) or food (other organisms).

• Energy Storage: Organisms store glucose as glycogen (animals) or starch (plants).

Oxidation of Glucose: Cellular Respiration vs. Fermentation

Glucose oxidation in cells occurs through a series of controlled redox reactions, releasing energy used to synthesize ATP. Cellular respiration fully oxidizes glucose, while fermentation only partially oxidizes it, resulting in less energy production.

• Cellular Respiration: Produces more ATP by fully oxidizing glucose to CO2.

• Fermentation: Produces ATP without fully oxidizing glucose, resulting in small, reduced organic molecules as waste.

Four Steps of Cellular Respiration

Cellular respiration consists of four main processes:

1. Glycolysis: Breakdown of glucose into two pyruvate molecules.

2. Pyruvate Processing: Oxidation of pyruvate to form acetyl CoA.

3. Citric Acid Cycle: Oxidation of acetyl CoA to CO2.

4. Electron Transport and Oxidative Phosphorylation: Electrons move through a transport chain, creating a proton gradient used to make ATP.

Metabolic Pathways: Catabolic and Anabolic Interactions

Cellular respiration interacts with other metabolic pathways. Catabolic pathways break down molecules to harvest energy, while anabolic pathways synthesize larger molecules using ATP.

• Catabolic Pathways: Breakdown of carbohydrates, fats, and proteins for ATP production.

• Anabolic Pathways: Use intermediates from cellular respiration to synthesize macromolecules (e.g., nucleotides, fatty acids, amino acids).

Glycolysis: Oxidizing Glucose to Pyruvate

Glycolysis is a sequence of 10 reactions occurring in the cytosol. It begins with an energy investment phase (using 2 ATP) and ends with an energy payoff phase (producing NADH and ATP by substrate-level phosphorylation).

• Net Yield: 2 NADH, 2 ATP, and 2 pyruvate per glucose.

• Substrate-Level Phosphorylation: Direct transfer of a phosphate group to ADP by an enzyme.

Table: The Reactions of Glycolysis

Step	Enzyme	Reaction
1	Hexokinase	Uses ATP to phosphorylate glucose, increasing its potential energy.
2	Phosphoglucose isomerase	Converts glucose-6-phosphate to fructose-6-phosphate.
3	Phosphofructokinase	Uses ATP to phosphorylate fructose-6-phosphate.
4	Fructose-bis-phosphate aldolase	Cleaves fructose-1,6-bisphosphate into two 3-carbon sugars.
5	Triose phosphate isomerase	Converts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate.
6	Glyceraldehyde-3-phosphate dehydrogenase	Oxidizes G3P, produces NADH, and attaches a phosphate to form 1,3-bisphosphoglycerate.
7	Phosphoglycerate kinase	Transfers a phosphate to ADP to make ATP.
8	Phosphoglycerate mutase	Rearranges phosphate to make 2-phosphoglycerate.
9	Enolase	Removes water to form phosphoenolpyruvate.
10	Pyruvate kinase	Transfers phosphate to ADP to make pyruvate and ATP.

Regulation of Glycolysis

Glycolysis is regulated by feedback inhibition, primarily at the phosphofructokinase step. High ATP levels inhibit the enzyme, slowing glycolysis.

Processing Pyruvate to Acetyl CoA

Pyruvate produced by glycolysis is transported into mitochondria (eukaryotes) and processed by pyruvate dehydrogenase. One carbon is oxidized to CO2, NADH is produced, and the remaining two-carbon unit is attached to coenzyme A, forming acetyl CoA.

The Citric Acid Cycle: Oxidizing Acetyl CoA to CO2

Each acetyl CoA is oxidized into two CO2 molecules in the citric acid cycle, located in the mitochondrial matrix (eukaryotes) or cytosol (prokaryotes). The cycle starts with acetyl CoA combining with oxaloacetate to form citrate and ends with regeneration of oxaloacetate.

• Energy Yield: Reduces NAD+ to NADH, FAD to FADH2, and phosphorylates ADP (or GDP) to ATP (or GTP).

• Cycle Turns: Twice per glucose molecule.

Table: The Reactions of the Citric Acid Cycle

Step	Enzyme	Reaction
1	Citrate synthase	Transfers acetyl group to oxaloacetate to produce citrate.
2	Aconitase	Converts citrate to isocitrate.
3	Isocitrate dehydrogenase	Oxidizes isocitrate, produces NADH, releases CO2.
4	α-Ketoglutarate dehydrogenase	Oxidizes α-ketoglutarate, produces NADH, releases CO2, forms succinyl CoA.
5	Succinyl-CoA synthetase	Converts succinyl CoA to succinate, produces ATP or GTP.
6	Succinate dehydrogenase	Oxidizes succinate, produces FADH2.
7	Fumarase	Converts fumarate to malate.
8	Malate dehydrogenase	Oxidizes malate, produces NADH, regenerates oxaloacetate.

Electron Transport Chain and Chemiosmosis

The electron transport chain (ETC) consists of four protein complexes and two mobile carriers (ubiquinone/Q and cytochrome c). Electrons from NADH and FADH2 are transferred through the ETC, releasing energy used to pump protons across the membrane, creating a proton gradient.

• ATP Synthase: Uses the proton-motive force to synthesize ATP from ADP and inorganic phosphate.

• Oxidative Phosphorylation: ATP production driven by the ETC and chemiosmosis.

• Yield: About 29 ATP per glucose molecule.

Fermentation: An Alternative Pathway

When oxygen is unavailable, cells use fermentation to regenerate NAD+ from NADH, allowing glycolysis to continue. Fermentation is less efficient, producing only 2 ATP per glucose.

• Lactic Acid Fermentation: Pyruvate accepts electrons from NADH, forming lactate.

• Alcohol Fermentation: Pyruvate is converted to acetaldehyde, which accepts electrons from NADH, forming ethanol.

• Facultative Anaerobes: Organisms that can switch between fermentation and aerobic respiration.

Summary Table: Cellular Respiration vs. Fermentation

Process	ATP Yield	Final Electron Acceptor	Products
Cellular Respiration	~29 ATP	Oxygen (aerobic) or other molecules (anaerobic)	CO2, H2O
Fermentation	2 ATP	Organic molecules (e.g., pyruvate, acetaldehyde)	Lactate or ethanol

Key Equations

• Cellular Respiration: $\text{C}_6\text{H}_{12}\text{O}_6 + 6\text{O}_2 \rightarrow 6\text{CO}_2 + 6\text{H}_2\text{O} + \text{ATP}$

• Fermentation (Lactic Acid): $\text{C}_6\text{H}_{12}\text{O}_6 \rightarrow 2\text{C}_3\text{H}_6\text{O}_3 + 2\text{ATP}$

• Fermentation (Alcohol): $\text{C}_6\text{H}_{12}\text{O}_6 \rightarrow 2\text{C}_2\text{H}_5\text{OH} + 2\text{CO}_2 + 2\text{ATP}$

Regulation and Homeostasis

Metabolic pathways are regulated by feedback inhibition and phosphorylation, maintaining homeostasis and adapting to environmental changes.

Applications and Human Angle

Metabolic reprogramming is observed in cancer cells, where alternative energy sources (e.g., alanine) are used. Inhibiting key enzymes in these pathways can reduce cancer cell growth, as demonstrated in liver cancer research.

Conclusion

Cellular respiration and fermentation are central to energy production in cells, integrating catabolic and anabolic pathways, and are tightly regulated to ensure efficient ATP synthesis and metabolic balance.