Cellular Respiration and Fermentation

Overview of Cellular Respiration

Cellular respiration is a fundamental metabolic process that provides energy for life by converting biochemical energy from nutrients into adenosine triphosphate (ATP), and releasing waste products. It is essential for both autotrophic and heterotrophic organisms.

• Life requires energy to perform cellular functions.

• The primary goal of cellular respiration is to produce ATP and NADH.

• Metabolic pathways harvest energy from high-energy molecules, such as glucose.

• Aerobic respiration uses oxygen as the final electron acceptor.

• O2 is consumed and CO2 is released during aerobic respiration.

ATP and Glucose in Cells

ATP is the immediate energy currency of the cell, but it is unstable and must be continually synthesized. Glucose serves as a primary substrate for ATP production.

• Cells generally contain enough ATP for only a few seconds to minutes of activity.

• ATP is unstable; most cells are constantly synthesizing it.

• Cells obtain glucose by:

  • Plants: Photosynthesis produces glucose.

  • Other organisms: Obtain glucose from food.

• Glucose is stored as glycogen (animals) or starch (plants).

What Happens When Glucose Is Oxidized?

Glucose oxidation is a redox process that releases energy, which is captured in the form of ATP. Complete oxidation of glucose can be represented by the following equation:

• When glucose is oxidized to carbon dioxide, energy is released as heat and light (in combustion):

• In cells, glucose is oxidized through a series of controlled redox reactions.

• The released free energy is used to synthesize ATP.

• These reactions comprise cellular respiration.

• Fermentation also oxidizes glucose, but not completely; it produces small, reduced organic molecules as waste and less energy than cellular respiration.

Stages of Cellular Respiration

Cellular respiration consists of four main metabolic pathways, each with specific roles and locations within the cell.

• The overall reaction for cellular respiration is:

• The four metabolic pathways are:

  1. Glycolysis

  2. Breakdown of pyruvate

  3. Citric acid cycle

  4. Oxidative phosphorylation

Cellular Respiration and Metabolism

Cellular respiration is central to metabolism, linking catabolic and anabolic 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.

Catabolic Pathways and Substrate Utilization

Cells can use carbohydrates, fats, and proteins as substrates for cellular respiration, integrating various metabolic pathways.

• Cells preferentially use carbohydrates first, then fats, and finally proteins for ATP production.

• Fats are broken down into glycerol (enters glycolysis) and fatty acids (converted to acetyl-CoA via beta-oxidation).

• Proteins are broken down into amino acids; amino groups are removed and excreted, and the remaining carbon skeletons enter glycolysis or the citric acid cycle.

Metabolic Intermediates and Anabolism

Intermediates from catabolic pathways can be diverted for anabolic processes, such as the synthesis of amino acids, nucleotides, and lipids.

• Metabolic pathways are highly regulated to maintain homeostasis—a stable internal environment.

Detailed Stages of Cellular Respiration

Glycolysis

Glycolysis is the first stage of cellular respiration and occurs in the cytosol. It can proceed with or without oxygen and is highly conserved across species.

• Divided into three phases:

  1. Energy investment phase (steps 1-3): ATP is used to phosphorylate glucose and its intermediates.

  2. Cleavage phase (steps 4-5): The six-carbon molecule is split into two three-carbon molecules.

  3. Energy liberation phase (steps 6-10): ATP and NADH are produced.

• Net yield per glucose: 2 ATP (via substrate-level phosphorylation), 2 NADH, and 2 pyruvate.

Substrate-Level Phosphorylation

• ATP is produced directly by the transfer of a phosphate group from a phosphorylated substrate to ADP.

Regulation of Glycolysis

• Regulated by feedback inhibition, primarily at the enzyme phosphofructokinase.

• High levels of ATP inhibit phosphofructokinase by binding to a regulatory site, slowing glycolysis.

Clinical Relevance: Warburg Effect

• Cancer cells often exhibit high rates of glycolysis (Warburg effect), even in the presence of oxygen.

• This is used in PET scans to diagnose cancers.

Breakdown of Pyruvate

Pyruvate produced in glycolysis is transported into the mitochondrial matrix (in eukaryotes) and converted to acetyl-CoA.

• Each pyruvate (3C) loses one carbon as CO2, forming an acetyl group (2C) that attaches to coenzyme A (CoA).

• One NADH is produced per pyruvate.

• This step is catalyzed by the pyruvate dehydrogenase complex.

• Regulated by feedback inhibition: when products accumulate, pyruvate dehydrogenase is phosphorylated and inhibited.

Citric Acid Cycle (Krebs Cycle)

The citric acid cycle completes the oxidation of glucose derivatives and generates high-energy electron carriers.

• Occurs in the mitochondrial matrix (eukaryotes) or cytosol (prokaryotes).

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

• Cycle regenerates oxaloacetate at the end.

• For each acetyl-CoA (per turn):

  • 3 NAD+ reduced to 3 NADH

  • 1 FAD reduced to 1 FADH2

  • 1 ATP (or GTP) produced by substrate-level phosphorylation

  • 2 CO2 released

• Cycle turns twice per glucose molecule.

• Regulated by feedback inhibition (NADH and ATP inhibit key enzymes).

Oxidative Phosphorylation

This stage uses high-energy electrons from NADH and FADH2 to generate ATP via the electron transport chain (ETC) and chemiosmosis.

• Occurs in the inner mitochondrial membrane.

• Electron transport chain consists of four protein complexes (I-IV) and mobile carriers (ubiquinone/Q and cytochrome c).

• Electrons are transferred through the chain, ultimately reducing O2 to H2O.

• Electron flow generates a proton (H+) gradient (proton-motive force) across the membrane.

• ATP synthase uses this gradient to synthesize ATP from ADP and Pi (chemiosmosis).

• Maximum yield: up to 30-34 ATP per glucose (actual yield is often lower due to use of intermediates in other pathways).

ATP Synthase Mechanism

• ATP synthase is a rotary enzyme that undergoes conformational changes as protons flow through it, driving ATP synthesis.

Aerobic vs. Anaerobic Respiration

Respiration can be classified based on the final electron acceptor used in the electron transport chain.

• Aerobic respiration: O2 is the final electron acceptor (most efficient, produces most ATP).

• Anaerobic respiration: Other molecules (e.g., nitrate) serve as final electron acceptors (less efficient).

• Oxygen's high electronegativity allows for a large proton-motive force and high ATP yield.

Fermentation

Fermentation is an anaerobic process that allows glycolysis to continue by regenerating NAD+ in the absence of an electron transport chain.

• Occurs when no suitable electron acceptor is available for the ETC.

• NADH produced in glycolysis transfers electrons to an organic molecule (e.g., pyruvate), regenerating NAD+.

• Allows ATP production by substrate-level phosphorylation to continue.

• Yields only 2 ATP per glucose (much less efficient than cellular respiration).

Types of Fermentation

• Lactic acid fermentation: Pyruvate accepts electrons from NADH, forming lactate (e.g., in muscle cells during intense exercise).

• Alcohol fermentation: Pyruvate is converted to acetaldehyde and CO2; acetaldehyde accepts electrons from NADH, forming ethanol (e.g., in yeast).

• Other fermentation pathways are used in food production (e.g., yogurt, cheese) and by prokaryotes in the gut.

Facultative Anaerobes

• Some organisms can switch between fermentation and aerobic respiration depending on oxygen availability.

Summary Table: Comparison of Cellular Respiration and Fermentation

Key Terms

• ATP (Adenosine Triphosphate): The main energy currency of the cell.

• NADH/FADH2: Electron carriers that store energy used to make ATP.

• Glycolysis: The breakdown of glucose to pyruvate, producing ATP and NADH.

• Citric Acid Cycle: A series of reactions that generate electron carriers and CO2 from acetyl-CoA.

• Oxidative Phosphorylation: Production of ATP using energy derived from the electron transport chain and chemiosmosis.

• Fermentation: Anaerobic process that regenerates NAD+ to allow glycolysis to continue.

• Substrate-level phosphorylation: Direct synthesis of ATP by transferring a phosphate group to ADP from a phosphorylated intermediate.

• Feedback inhibition: Regulatory mechanism in which the end product of a pathway inhibits an upstream process.