Cellular Respiration and Fermentation

Introduction to Cellular Energy Production

Cells require energy to perform essential functions, and this energy is primarily supplied by adenosine triphosphate (ATP). Cellular respiration and fermentation are the main metabolic pathways that harvest energy from high-energy molecules such as glucose. The energy released during these processes is used to add a phosphate group to ADP, forming ATP, which fuels cellular work.

Overview of Cellular Respiration

Cellular respiration is a series of metabolic reactions that convert biochemical energy from nutrients into ATP. Cells typically contain enough ATP for only a short duration and must continually synthesize it. Glucose, obtained from photosynthesis in plants or food in other organisms, is the primary substrate for ATP production. Organisms store glucose as glycogen (animals) or starch (plants).

Oxidation of Glucose

When glucose is oxidized, energy is released. In cells, this occurs through a series of controlled redox reactions, collectively known as cellular respiration. Most of the energy released is used to synthesize ATP. Fermentation is an alternative pathway that also oxidizes glucose but does not fully oxidize it, resulting in less energy production and the formation of small, reduced organic molecules as waste.

Major Steps of Cellular Respiration

Cellular respiration consists of four main processes:

1. Glycolysis: A six-carbon glucose molecule is broken down into two three-carbon pyruvate molecules.

2. Pyruvate Processing: Each pyruvate is oxidized to form acetyl CoA.

3. Citric Acid Cycle: Each acetyl CoA is oxidized to CO2.

4. Electron Transport and Oxidative Phosphorylation: Electrons move through a transport chain, and their energy is used to set up a proton gradient, which drives ATP synthesis.

Catabolic and Anabolic Pathways

Metabolism is divided into two types of pathways:

• Catabolic pathways: Break down molecules and harvest stored chemical energy to produce ATP.

• Anabolic pathways: Synthesize larger molecules from smaller components, often using ATP as an energy source.

Glycolysis

Process and Regulation

Glycolysis is a sequence of 10 reactions occurring in the cytosol. It consists of two phases:

• Energy investment phase (reactions 1–5): Uses two ATP molecules.

• Energy payoff phase (reactions 6–10): Produces four ATP (net gain of two ATP), two NADH, and two pyruvate molecules via substrate-level phosphorylation.

Glycolysis is regulated by feedback inhibition of the enzyme phosphofructokinase. High ATP levels inhibit this enzyme, slowing glycolysis when energy is abundant.

Pyruvate Processing

Conversion to Acetyl CoA

In eukaryotes, pyruvate produced by glycolysis is transported into the mitochondria, where it is processed by the enzyme pyruvate dehydrogenase in the mitochondrial matrix. One carbon from pyruvate is released as CO2, NADH is produced, and the remaining two-carbon unit is attached to coenzyme A, forming acetyl CoA.

Pyruvate processing is regulated by phosphorylation: high levels of NADH, acetyl CoA, or ATP increase phosphorylation (inhibiting the enzyme), while high levels of ADP, pyruvate, CoA, or NAD+ increase dephosphorylation (activating the enzyme).

The Citric Acid Cycle (Krebs Cycle)

Oxidation of Acetyl CoA

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

• Reduces three NAD+ to NADH

• Reduces one FAD to FADH2

• Phosphorylates ADP (or GDP) to form ATP (or GTP)

• Turns twice per glucose molecule

The cycle is regulated by feedback inhibition: high ATP or NADH levels slow the cycle, while low levels increase its rate.

Electron Transport Chain and Chemiosmosis

Electron Transport Chain (ETC)

The electron transport chain (ETC) is a series of protein complexes and other molecules embedded in the inner mitochondrial membrane. NADH and FADH2 donate electrons to the ETC, which are transferred through a series of redox reactions. The energy released is used to pump protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient.

ATP Synthase and Chemiosmosis

The proton gradient generated by the ETC creates a proton-motive force. Protons flow back into the matrix through ATP synthase, a protein complex that synthesizes ATP from ADP and inorganic phosphate (Pi). This process is called chemiosmosis and is responsible for most of the ATP produced during cellular respiration.

ATP Yield

Oxidative phosphorylation (ETC and chemiosmosis) produces about 25–29 ATP per glucose molecule, compared to 4 ATP from substrate-level phosphorylation in glycolysis and the citric acid cycle.

Fermentation

Fermentation Pathways

When oxygen or another suitable electron acceptor is not available, cells use fermentation to regenerate NAD+ from NADH, allowing glycolysis to continue. Fermentation produces much less ATP (2 ATP per glucose) than cellular respiration (about 29 ATP per glucose).

• Lactic acid fermentation: Pyruvate accepts electrons from NADH, forming lactate and regenerating NAD+ (occurs in muscle cells).

• Alcohol fermentation: In yeast, pyruvate is converted to acetaldehyde and CO2; acetaldehyde accepts electrons from NADH, forming ethanol and regenerating NAD+.

Some organisms can switch between fermentation and aerobic respiration (facultative anaerobes), using fermentation only when oxygen is unavailable.

Metabolic Integration and Homeostasis

Catabolic Pathways for Other Molecules

Cellular respiration is interconnected with the metabolism of carbohydrates, fats, and proteins. Fats are broken down into glycerol (enters glycolysis) and fatty acids (converted to acetyl CoA). Proteins are broken down into amino acids, which are deaminated and converted into intermediates of glycolysis or the citric acid cycle.

Anabolic Pathways and Homeostasis

Intermediates from cellular respiration are used in anabolic pathways to synthesize macromolecules such as nucleotides, amino acids, and fatty acids. The regulation of these pathways maintains cellular homeostasis, ensuring a stable internal environment under varying conditions.

Summary Table: Cellular Respiration Pathways