Cellular Respiration and Fermentation: Study Guide

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, through exergonic catabolic reactions. This process is essential for the production of ATP, the energy currency of the cell.

• Aerobic respiration: Utilizes oxygen as the final electron acceptor, producing water and a high yield of ATP.

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

• Fermentation: Occurs in the absence of an electron transport chain; regenerates NAD+ by transferring electrons to organic acceptors, yielding less ATP.

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

Redox Reactions in Cellular Respiration

Cellular respiration involves a series of oxidation-reduction (redox) reactions, where electrons are transferred from fuel molecules to electron carriers and ultimately to oxygen.

• Oxidation: Loss of electrons from a molecule.

• Reduction: Gain of electrons by a molecule.

• Balanced equation for glucose catabolism:

$\mathrm{C_6H_{12}O_6 + 6O_2 \rightarrow 6CO_2 + 6H_2O + Energy}$

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

• Redox reactions may not involve direct electron transfer between atoms but often involve changes in electron sharing due to electronegativity differences.

Electron Carriers: NAD+ and FAD

NAD+ and FAD are coenzymes that function as primary electron carriers in cellular respiration.

• NAD+/NADH redox reaction:

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

• Dehydrogenases are enzymes that facilitate the transfer of electrons from substrates to NAD+ or FAD.

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

Stages of Cellular Respiration

Cellular respiration consists of three main stages:

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

2. Pyruvate oxidation and the citric acid cycle (mitochondrion): Converts pyruvate to acetyl-CoA, then oxidizes it to CO2 in the citric acid cycle.

3. Oxidative phosphorylation (mitochondrion): Includes the electron transport chain and chemiosmosis, generating most ATP.

ATP Synthesis: Oxidative vs. Substrate-Level Phosphorylation

• Oxidative phosphorylation: Uses energy from electron carriers (NADH, FADH2) to drive ATP synthesis via the ETC and chemiosmosis.

• Substrate-level phosphorylation: Direct transfer of a phosphate group from a substrate to ADP, forming ATP (occurs in glycolysis and the citric acid cycle).

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

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

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

• Glycolysis does not require oxygen.

Energy Investment Phase

• ATP is used to phosphorylate glucose and fructose-6-phosphate.

• Aldolase: Splits fructose-1,6-bisphosphate into two 3-carbon sugars.

• Isomerase: Converts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate.

Energy Payoff Phase

• Triose phosphate isomerase: Interconverts 3-carbon sugars, facilitating NAD+ reduction to NADH.

• Phosphoglycerokinase and pyruvate kinase: Catalyze substrate-level phosphorylation, generating ATP.

Glycolysis Energy Summary

• Total energy investment: 2 ATP

• Total energy output: 4 ATP (gross), 2 NADH

• Net energy output: 2 ATP, 2 NADH

Pyruvate Oxidation

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

• Substrates: Pyruvate, NAD+, Coenzyme A

• Products: Acetyl-CoA, NADH, CO2

• Energy is stored as NADH (no ATP is produced directly).

• Pyruvate is a 3-carbon alpha-keto acid.

The Citric Acid Cycle (Krebs Cycle)

The citric acid cycle completes the oxidation of acetyl-CoA, generating CO2, NADH, FADH2, and GTP/ATP.

• Initial substrate: Acetyl-CoA

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

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

• The cycle regenerates oxaloacetate, allowing continuous operation.

Key Steps

• Entry: Acetyl group combines with oxaloacetate to form citrate.

• Production of succinyl-CoA: Generates NADH and CO2.

• Production of fumarate: Generates GTP (converted to ATP) and FADH2.

• Regeneration of oxaloacetate: Generates NADH.

Oxidative Phosphorylation: Electron Transport Chain and Chemiosmosis

Oxidative phosphorylation uses the energy from NADH and FADH2 to generate ATP via the electron transport chain (ETC) and chemiosmosis.

• Location: Inner mitochondrial membrane

• Major 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

• Electron transfer drives H+ pumping, creating a proton gradient across the inner membrane.

• Complexes I, III, and IV act as proton pumps.

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

Chemiosmosis: 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

Stage	ATP	NADH	FADH2
Glycolysis	2	2	0
Pyruvate Oxidation	0	2	0
Citric Acid Cycle	2	6	2
Oxidative Phosphorylation	~26-28	0	0

• Total ATP per glucose: 30-32 (exact number varies due to shuttle mechanisms and membrane permeability).

• 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 and regenerate NAD+.

• Fermentation: Glycolysis followed by NAD+ regeneration via reduction of pyruvate or its derivatives.

• Alcohol fermentation: Pyruvate is converted to ethanol (used by yeast).

• Lactic acid fermentation: Pyruvate is reduced to lactate (used by muscle cells, some bacteria).

• Both processes use substrate-level phosphorylation for ATP production.

• Anaerobic respiration: Uses an electron transport chain with a final electron acceptor other than O2 (e.g., nitrate, sulfate).

• Organisms: Many prokaryotes (e.g., Escherichia coli in anaerobic conditions).

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

Integrative Metabolism: Catabolic and Anabolic Pathways

Cellular respiration is interconnected with other metabolic pathways, allowing cells to utilize various biomolecules for energy and biosynthesis.

• 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 than twice as much ATP per gram as 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 ATP, NADH, FADH2, and intermediates from cellular respiration to synthesize new biomolecules.