Cellular Respiration and Fermentation: Study Notes

Chapter 7: Cellular Respiration and Fermentation

Overview of Cellular Respiration

Cellular respiration is a series of metabolic processes by which cells harvest chemical energy from organic molecules, primarily glucose. This process involves a sequence of exergonic catabolic reactions that ultimately produce ATP, the cell's main energy currency.

• Aerobic respiration: Utilizes oxygen as the final electron acceptor; yields the most ATP.

• Anaerobic respiration: Uses other molecules (not O2) as final electron acceptors; less efficient than aerobic respiration.

• Fermentation: Partial degradation of sugars without the use of an electron transport chain; yields much less ATP.

• Note: The terms "cellular respiration" and "aerobic respiration" are often used interchangeably.

Redox Reactions in Cellular Respiration

Cellular respiration is fundamentally a series of oxidation-reduction (redox) reactions, where electrons are transferred from one molecule to another.

• Oxidation: Loss of electrons from a substance.

• Reduction: Gain of electrons by a substance.

• Balanced equation for glucose catabolism:

$\mathrm{C_6H_{12}O_6} + 6\ \mathrm{O_2} \rightarrow 6\ \mathrm{CO_2} + 6\ \mathrm{H_2O} + \text{Energy (ATP + heat)}$

• Glucose is oxidized to CO2; O2 is reduced to H2O.

• Redox reactions may not involve direct electron transfer between atoms but rather changes in electron sharing in covalent bonds.

• Electronegative atoms (like O) are essential as they attract electrons, facilitating energy release.

Electron Carriers: NAD+ and FAD

Electron carriers temporarily store energy as electrons during cellular respiration.

• NAD+/NADH: Primary electron carrier in the electron transport chain.

• FAD/FADH2: Another important electron carrier.

• Redox reaction for NAD+:

$\mathrm{NAD^+} + 2\ \mathrm{e^-} + 2\ \mathrm{H^+} \rightarrow \mathrm{NADH} + \mathrm{H^+}$

• Dehydrogenase enzymes facilitate the transfer of electrons and protons to NAD+ or FAD.

• NADH and FADH2 shuttle electrons to the electron transport chain.

Stepwise Electron Transfer and the Electron Transport Chain (ETC)

Electrons are transferred to oxygen in a stepwise manner via the ETC, preventing the release of excessive heat and allowing controlled ATP synthesis.

• Direct transfer would release energy as heat; stepwise transfer allows energy capture as ATP.

Stages of Cellular Respiration

Cellular respiration occurs in three main stages:

• Glycolysis (cytosol): Splits glucose into two pyruvate molecules.

• Pyruvate oxidation and Citric Acid Cycle (mitochondrion): Converts pyruvate to CO2 and generates electron carriers.

• Oxidative phosphorylation (mitochondrion): Includes the ETC and chemiosmosis, producing most ATP.

ATP Synthesis: Oxidative vs. Substrate-Level Phosphorylation

• Substrate-level phosphorylation: Direct transfer of a phosphate group to ADP from a phosphorylated intermediate.

• Oxidative phosphorylation: ATP synthesis powered by redox reactions in the ETC, utilizing electron carriers (NADH, FADH2).

Glycolysis

Glycolysis is the metabolic pathway that breaks down glucose into pyruvate, generating ATP and NADH.

• Initial substrates: Glucose, 2 ATP, 2 NAD+, 4 ADP + 4 Pi

• Key steps:

  • "Sugar-splitting": 6-carbon glucose is split into two 3-carbon molecules (glyceraldehyde-3-phosphate).

  • Energy investment phase: 2 ATP are used to phosphorylate intermediates (hexokinase, phosphofructokinase).

  • Enzymes: Aldolase splits fructose-1,6-bisphosphate; isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.

  • Energy payoff phase: 4 ATP produced (net gain 2 ATP), 2 NADH generated.

  • Phosphoglycerokinase and pyruvate kinase catalyze substrate-level phosphorylation steps.

• End products: 2 pyruvate, 2 net ATP, 2 NADH, 2 H2O, 2 H+

• Oxygen requirement: Glycolysis does not require oxygen (anaerobic process).

Pyruvate Oxidation

Pyruvate oxidation links glycolysis to the citric acid cycle, converting pyruvate into acetyl-CoA.

• Location: Mitochondrial matrix

• Reaction: Pyruvate + CoA + NAD+ → Acetyl-CoA + CO2 + NADH + H+

• Energy: NAD+ is reduced to NADH.

• Pyruvate structure: 3-carbon alpha-keto acid.

The Citric Acid Cycle (Krebs Cycle)

The citric acid cycle completes the oxidation of organic molecules, generating CO2, NADH, FADH2, and GTP/ATP.

• Initial substrate: Acetyl-CoA

• Cycle steps:

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

  • Through a series of reactions, citrate is converted back to oxaloacetate, releasing 2 CO2.

  • Key products per acetyl-CoA: 3 NADH, 1 FADH2, 1 GTP (or ATP), 2 CO2

  • For one glucose (2 acetyl-CoA): 6 NADH, 2 FADH2, 2 GTP/ATP, 4 CO2

  • GTP can be converted to ATP.

  • Cycle regenerates oxaloacetate, allowing continuous operation.

Oxidative Phosphorylation: Electron Transport Chain and Chemiosmosis

Oxidative phosphorylation is the main ATP-producing stage, involving the electron transport chain (ETC) and chemiosmosis.

• Location: Inner mitochondrial membrane

• Major ETC complexes: I (NADH dehydrogenase), II (succinate dehydrogenase), III (cytochrome bc1), IV (cytochrome c oxidase)

• Cytochromes: Proteins with heme groups that transfer electrons within the ETC.

• Final electron acceptor: O2, forming H2O.

• Proton gradient: ETC complexes I, III, IV pump H+ from the matrix to the intermembrane space, creating an electrochemical gradient.

• ATP synthase: Utilizes the proton-motive force (chemiosmosis) to synthesize ATP from ADP and Pi.

Definition: Chemiosmosis is the process by which energy stored in a proton gradient is used to drive cellular work, such as ATP synthesis.

ATP, NADH, and FADH2 Yield from Glucose

The total yield of energetic molecules from one glucose molecule varies due to cellular conditions.

Stage	ATP (net)	NADH	FADH2
Glycolysis	2	2	0
Pyruvate Oxidation	0	2	0
Citric Acid Cycle	2	6	2
Oxidative Phosphorylation	~26-28	0	0
Total	~30-32	10	2

• Exact ATP yield (30 or 32) varies due to shuttle mechanisms and membrane permeability.

• Overall efficiency: About 34% of glucose energy is captured as ATP; the rest is lost as heat.

Fermentation and Anaerobic Respiration

When oxygen is unavailable, cells use fermentation or anaerobic respiration to generate ATP.

• Fermentation: Extension of glycolysis; regenerates NAD+ by transferring electrons to organic acceptors.

• Alcohol fermentation: Pyruvate is converted to ethanol; used by yeast and some bacteria.

• Lactic acid fermentation: Pyruvate is reduced to lactate; used by muscle cells and some bacteria.

• Both processes use substrate-level phosphorylation for ATP and regenerate NAD+ for glycolysis.

• Anaerobic respiration: Uses an ETC with a final electron acceptor other than O2 (e.g., nitrate, sulfate); found in some prokaryotes.

• Evolutionary significance: Glycolysis is an ancient pathway, present in nearly all organisms.

Integration of Metabolic Pathways

Cellular respiration is interconnected with other catabolic and anabolic pathways.

• Carbohydrates: Must undergo glycolysis before entering the citric acid cycle.

• Lipids: Broken down into glycerol (enters glycolysis) and fatty acids (converted to acetyl-CoA via beta-oxidation); fats yield more ATP per gram than carbohydrates.

• Proteins: Deaminated amino acids can enter at various points (end of glycolysis, as acetyl-CoA, or directly into the citric acid cycle); ammonia (NH3/NH4+) is produced as waste and converted to urea.

• Anabolic pathways: Use intermediates and energy from cellular respiration to synthesize new biomolecules.