Cellular Respiration Notes

Cellular Respiration

Overview

• Cellular respiration, electron transport, and oxidative phosphorylation are key processes in harvesting chemical energy.
• Cells require energy from external sources for:
  • Macromolecule synthesis
  • Active transport
  • Movement
  • Reproduction
• Catabolic pathways:
  • Produce ATP by breaking down organic compounds.
  • Example: Cellular respiration
• Anabolic pathways:
  • Consume energy to synthesize organic compounds (biosynthesis).
  • Example: Photosynthesis
• Mitochondria and chloroplasts are organelles involved in energy production and conversion.

Energy Flow

• Sunlight is the primary energy source for ecosystems.
• Energy enters as sunlight and exits as heat.
• Photosynthesis occurs in chloroplasts.
• Cellular respiration occurs in mitochondria.

ATP Production

• Cells regenerate ATP to function.
• Catabolic pathways oxidize organic fuels to produce energy.
• The breakdown of organic molecules is exergonic (ΔG < 0), releasing energy as ATP.

Catabolic Pathways

• Two major cellular catabolic processes:
  • Cellular Respiration (Aerobic):
    • Efficient degradation of carbohydrates in the presence of oxygen.
    • Yields a high amount of ATP.
  • Anaerobic Respiration (Fermentation):
    • Partial degradation of carbohydrates in the absence of oxygen.
    • Yields a low amount of ATP.

Cellular Respiration

• Encompasses both aerobic and anaerobic respiration but usually refers to aerobic respiration.
• Energy conversion:
  • Chemical energy in glucose bonds is transferred to phosphate bonds in ATP.
• Energy from ATP hydrolysis (exergonic) fuels cellular work (endergonic).

Photosynthesis and Cellular Respiration Equations

• Photosynthesis: $CO<em>2 + H</em>2O \rightarrow C<em>6H</em>{12}O<em>6 + O</em>2$
• Cellular Respiration (Aerobic): $C<em>6H</em>{12}O<em>6 + O</em>2 \rightarrow CO<em>2 + H</em>2O + ATP$

ATP

• ATP is a nucleotide that stores energy in phosphate bonds.
• It cycles between adenosine triphosphate (ATP) and adenosine diphosphate (ADP).

Molecule and Energy Exchange

• Photosynthesis (in chloroplasts) uses light energy, $CO<em>2$, and $H</em>2O$ to produce glucose and $O_2$.
• Aerobic respiration (in mitochondria) uses glucose and $O<em>2$ to produce $CO</em>2$, $H_2O$, and ATP.

Organelles

• Mitochondria and chloroplasts are energy production and conversion organelles.
• Cellular respiration produces energy from the oxidation of organic compounds.
• Chloroplasts conduct photosynthesis.
• Mitochondria handle two of three stages of cellular respiration:
  1. Glycolysis: in the cytosol
  2. Krebs Cycle (Citric Acid Cycle): in the mitochondrial matrix
  3. Oxidative Phosphorylation: in the inner mitochondrial membrane

Mitochondria Structure

• Diameter: 1-10 μm.
• Structure:
  • Outer membrane: contains porins and some enzymes (e.g., MAO).
  • Inner membrane: forms cristae and contains ETC complexes and ATP synthase.
  • Intermembrane space.
  • Matrix: contains mtDNA and free ribosomes.

Redox Reactions

• Catabolic pathways yield energy through electron transfer (redox reactions).
• Oxidation: a substance loses electrons and is oxidized.
• Reduction: a substance gains electrons and is reduced.

Redox Reactions Examples

• $Na + Cl \rightarrow Na^+ + Cl^-$
  • Na becomes oxidized (loses electron).
  • Cl becomes reduced (gains electron).
• $X^- + Y \rightarrow X + Y^-$
  • $X^-$ becomes oxidized (loses electron).
  • Y becomes reduced (gains electron).

Oxidation of Organic Fuel Molecules

• During cellular respiration, glucose is oxidized and $O_2$ is reduced.

Stages of Cellular Respiration

1. Glycolysis: anaerobic, in the cytosol.
2. Citric Acid Cycle.
3. Oxidative Phosphorylation: aerobic, in mitochondria.

Glycolysis

• Glucose breaks down into 2 molecules of pyruvate.

Citric Acid Cycle

• Pyruvate is converted to acetyl-CoA and broken down into $CO_2$.

Oxidative Phosphorylation

• Driven by the electron transport chain (ETC).
• ETC causes chemiosmosis, which generates ATP by ATP synthase.

ATP Production

• Glycolysis and the citric acid cycle generate some ATP (10%) via substrate-level phosphorylation.
• Most ATP (90%) is generated by oxidative phosphorylation (by ATP synthase).

Energy Transfer

• Energy from organic compounds is produced as electrons.
• Electron transport by redox coenzymes $NAD^+$ and FAD.
• Electrons released from oxidation are transferred:
  1. To coenzymes $NAD^+$ and FAD, reducing them to NADH and $FADH_2$.
  2. To the electron transport chain (ETC).
  3. Finally, to $O<em>2$ to produce $H</em>2O$.

Redox Coenzymes

• NAD = Nicotinamide adenine dinucleotide.
• FAD = Flavin adenine dinucleotide.

Redox Coenzymes (Detailed)

• Dehydrogenases: enzymes that remove $e^-$ from organic compounds (oxidized) and transfer them to $NAD^+$ or FAD.
• $NAD^+$ reduces to NADH.
• FAD reduces to $FADH_2$.

NAD+ Reduction Reaction

• Each $e^-$ is co-transferred with a proton ($H^+$, $H^+ + e^-$).

Cellular Respiration Stages

1. Glycolysis.
2. Citric Acid Cycle.
3. Oxidative Phosphorylation.

Glycolysis

• Means "splitting of sugar".
• Breaks down glucose (6C) into 2 molecules of pyruvate (3C).
• Occurs in the cytosol.
• Anaerobic (does not require oxygen).
• Products: 2 ATP, 2 NADH, 2 pyruvate molecules.
• ATP production: substrate-level phosphorylation.

Glycolysis Phases

1. Energy Investment Phase: ATP spent.
2. Energy Payoff Phase: ATP produced.

Energy Investment Phase

• 2 ATP are utilized.
• Substrates are phosphorylated, increasing their energy and instability, leading to glucose splitting.

Energy Payoff Phase

• Net products: 2 ATP, 2 NADH, 2 pyruvates.

Regulation Points

• Citric acid cycle: in mitochondrial matrix.
• Oxidative phosphorylation: inner mitochondrial membrane.
  1. Electron transport chain (ETC): on the inner mitochondrial membrane.
  2. Chemiosmosis: $H^+$ gradient drives ATP synthesis via ATP synthase (inner mitochondrial membrane). ATP synthesis in the matrix.

Citric Acid Cycle

• Takes place in the mitochondrial matrix.
• Completes oxidation of organic molecules, producing $CO_2$ and energy.
• Pyruvate converts into acetyl-CoA before the cycle.
• Production of Acetyl-coenzyme A (acetyl-CoA) by either glycolysis or β-oxidation of fatty acids  Acetyl-CoA enters Krebs cycle.

Pyruvate Conversion to Acetyl-CoA

• Pyruvate dehydrogenase catalyzing the conversion in the mitochondrion.

Citric Acid Cycle

• Pyruvate is broken down and $CO_2$ is released.
• Acetyl-CoA binds to oxaloacetate (OAA), producing citric acid.
• NADH and $FADH_2$ are produced and transferred to the ETC.

Krebs Cycle Products

• Each acetyl-CoA yields:
  • 2 $CO_2$.
  • 3 NADH.
  • 1 $FADH_2$.
  • 1 ATP.
• Krebs cycle energy gain: 1 ATP, 3 NADH, 1 $FADH_2$.
• Net energy profit: 12 ATP per Krebs cycle from 1 acetyl-CoA; 1 NADH yields 3 ATP, 1 $FADH_2$ yields 2 ATP.

Citric Acid Cycle Overview

• One glucose molecule produces 2 pyruvates upon glycolysis, yielding 2 acetyl-CoA.
• From one glucose molecule, the two citric acid cycles generate:
  • 4 $CO_2$.
  • 2 ATP.
  • 6 NADH.
  • 2 $FADH_2$.

Oxidative Phosphorylation

• NADH and $FADH_2$ donate electrons to the electron transport chain (ETC).
• ETC powers ATP synthesis - phosphorylation (ATP from ADP + Pi using ATP synthase).

Chemiosmosis

• Energy-coupling mechanism that uses the energy from an $H^+$ gradient across a membrane to drive ATP production.

Electron Transfer to ETC

• Electrons enter ETC via:
  • NADH oxidation through complex I (NADH dehydrogenase).
  • $FADH_2$ oxidation through complex II (succinate dehydrogenase).

Stepwise Energy Transfer

• Cellular respiration oxidizes glucose stepwise.
• If electron transfer isn't stepwise, energy releases explosively.

Electron Transport Chain

• Passes electrons stepwise instead of one explosive reaction.
• Uses electron transfer energy to form ATP.
• Each $e^-$ carrier is more electronegative than the last.

ETC details

• Electrons from oxidation of NADH and $FADH_2$ transfer to the ETC.
• Electrons transfer initially to ubiquinone.
• Electrons pass from higher to lower energy carriers.
• Electrons eventually transfer to $O<em>2$, forming $H</em>2O$.

Electron Transport Chain Complexes

1. Complex I: NADH dehydrogenase.
2. Complex II: Succinate dehydrogenase.
3. Coenzyme Q (CoQ): ubiquinone.
4. Complex III: cytochrome oxidoreductase.
5. Cytochrome c.
6. Complex IV: cytochrome oxidase.

Oxidative Phosphorylation & ETC

• Electrons from NADH and $FADH_2$ (from glycolysis and Krebs cycle) transfer to the ETC.
• $O<em>2$ accepts ETC electrons, producing $H</em>2O$.

Chemiosmosis Details

• ETC pumps $H^+$ to the intermembrane space, creating a $H^+$ concentration gradient.
• Electrochemical gradient between matrix (pH 8) and intermembrane space (pH 7).
• Membrane potential develops, leading to chemiosmosis.

ATP Production

• Higher $H^+$ concentration in the intermembrane space drives $H^+$ flow to the matrix via ATP synthase.
• ATP synthase uses this $H^+$ flow to produce ATP.

Proton-Motive Force

• ETC proteins pump $H^+$ from the mitochondrial matrix to the intermembrane space.
• The proton gradient (proton-motive force, PMF) drives chemiosmosis and ATP production.

Chemiosmosis

• ATP synthase makes ATP functioning as a pump running in reverse and is located in the inner mitochondrial membrane.

ATP Synthase

• Synthesizes ATP from ADP and Pi.
• Found in mitochondria, chloroplasts, and bacteria.
• Proton pump that uses the proton gradient to power ATP synthesis.
• Two parts:
  • $F_0$: transmembrane, subunits a, b, c.
  • $F_1$: matrix, subunits α, β, γ, δ, ε.
• Proton flow alters ATP/ADP binding affinity.

Process

• Binding of ADP and Pi, ATP synthesis, $120^\circ$ CCW rotation due to proton flow and ATP release.

Energy Flow

• Via redox reactions of electron transport chains, mitochondria generate a $H^+$ gradient across a membrane and ATP synthase uses this proton-motive force to make ATP.
• Glucose → NADH/$FADH_2$ → ETC → PMF → ATP.

Summary

• Synthesis of 1 ATP needs 3 protons flowing through ATP synthase.
• NADH oxidation transfers 10 protons, producing about 2.5 ATP.
• $FADH_2$ oxidation transfers 6 protons, producing about 1.5 ATP.
• Some ATP is used for transport to the cytosol.

Equations

• ATP production by NADH: $10H^+ / 3H^+ = 3.33$ ATP molecules.
• ATP production by $FADH_2$: $6H^+ / 3H^+ = 2$ ATP molecules.

ATP Production Numbers

• About 30-32 ATP produced from 1 glucose molecule. However other calculations show 36-38 molecules produced.

Final Tally

• Glycolysis products: 2 pyruvates, 2 ATP, 2 NADH.
• Citric acid cycle products per glucose molecule: 6 $CO<em>2$, 2 ATP, 8 NADH, 2 $FADH</em>2$.
• Oxidative phosphorylation: 32-34 ATP.
• Total: 36-38 ATP molecules.

Energy Gain

• Glycolysis: 2 ATP + 2 NADH.
• Pyruvate to Acetyl-CoA: 2 NADH.
• Citric acid cycle: 2 ATP, 6 NADH + 2 $FADH_2$.
• Oxidative phosphorylation: 30 ATP (from NADH) + 4 ATP (from $FADH_2$).
• Total: 38 ATP.

Notes

• But, ATP numbers are approximate because:
  1. Some ATP is used to move ATP to the cytosol.
  2. ATP depends on the electron shuttle to move electrons from cytosolic NADH. Electrons of cytosolic NADH can be passed either to mitochondrial $NAD^+$ (e.g. liver cells) or to mitochondrial FAD (e.g. brain cells).
  3. Energy is used for pyruvate transport into the mitochondrion.

Electron Transfers

• If cytosolic NADH electrons pass to mitochondrial $NAD^+$ (liver cells): 6 ATP (2 NADH x 3 ATP/NADH).
• If cytosolic NADH electrons pass to mitochondrial FAD (brain cells): 4 ATP (2 $FADH<em>2$ x 2 ATP/$FADH</em>2$).

Anaerobic Respiration

• Produces less ATP than aerobic (only 2 ATP).
• Glycolysis + Fermentation.

Aerobic and Anaerobic Respiration Side-by-Side

• Pyruvate determines the catabolic pathway.
• No $O_2$ present: Fermentation to ethanol or lactate.
• $O_2$ present: Cellular Respiration to Acetyl CoA, then Citric acid cycle.

Fermentation

• Lactic acid or alcohol production.
• $NAD^+$ regeneration reactions, which are reused by glycolysis so that ATP production continues.

Types of Fermentation

• Alcohol Fermentation:
  • Ethanol and $CO_2$ production in yeasts.
• Lactic Acid Fermentation:
  • Lactic acid production in animal cells.

Alcohol Fermentation (Details)

• Pyruvate converts into ethanol and $CO_2$.
• Applications: Wine, beer, bread making.
• Reaction: $C<em>6H</em>{12}O<em>6 \rightarrow 2 CH</em>3CH<em>2OH + 2 CO</em>2$

More Alcohol Fermentation Details

• Yeasts produce ethanol in alcoholic drinks.
• Baker’s yeast makes bread, and byproduct $CO_2$ causes bread to rise.

Lactic Acid Fermentation (Details)

• Lactic acid production in animal cells/bacteria.
• Pyruvate is directly reduced by NADH to form lactate.
• Reaction: $C<em>6H</em>{12}O<em>6 \rightarrow 2 CH</em>3CHOHCOOH$

Even More Details

• Occurs when there is limited oxygen.
• Example: Muscle fatigue under strenuous exercise. Lactate accumulation causes muscle fatigue.
• Application: bacteria convert lactose into lactic acid in yogurt.

Aerobic vs. Anaerobic Comparison

• Both use glycolysis to oxidize glucose and other organic fuels to pyruvate.
• Different final products (organic compound vs water).
• Aerobic respiration produces more ATP.
  • Aerobic: 38 ATP per glucose.
  • Anaerobic: 2 ATP per glucose.

Classification

• Obligate anaerobes: cannot survive in $O_2$.
• Facultative anaerobes: can survive with or without oxygen.

Catabolic Pathways Connection

• Proteins: Excess amino acids enter after losing their amino groups as $NH_3$.
• Lipids:
  • Glycerol (in fats) enters glycolysis.
  • Fatty acids enter the citric acid cycle as acetyl-CoA (β-oxidation product).

Anabolic Pathways

• Use ATP.
• The body synthesizes substances.
• Source of small molecules: food or from glycolysis/citric acid cycle.

Regulation

• Regulated via feedback mechanisms.
• Controlled by allosteric enzymes and feedback inhibition by ATP.

Control of Cellular Respiration

• Phosphofructokinase (PFK): major control point.
  • Allosteric enzyme.
  • Inhibited by ATP.
  • Inhibited by citrate.
  • Stimulated by AMP.

Clinical Correlations

• Diseases from insufficient ATP synthesis (ATP synthase mutations) cause severe neuromuscular disorders (e.g., Leigh and MELAS syndromes, cardiomyopathies, encephalomyopathies).
• Example: Leber’s optic neuropathy: complex I mutations.