Energy, Metabolism and Thermodynamics

• Energy is the capacity to do work.
• Organisms obtain energy through cellular respiration using carbohydrates and other energy-rich molecules.

Two States of Energy

• Kinetic energy is the energy of motion, including mechanical and electrical forms.
• Potential energy is stored energy, such as gravitational and chemical energy.

Metabolism

• Metabolism is the sum of all chemical reactions within a cell or organism.

Catabolism

• Catabolism involves breaking down complex molecules into simpler ones, releasing energy.
• An example reaction is C6H12O6 + 6O2 → 6CO2 + 6H2O.

Anabolism

• Anabolism involves building complex molecules from simpler ones, consuming energy.
• An example reaction is 6CO2 + 6H2O → C6H12O6.

Laws of Thermodynamics

• First Law: Energy cannot be created or destroyed, only converted from one form to another.
• Second Law: The universe tends toward disorder; entropy increases over time.

Bond Energy

• Bond energy measures the strength of a covalent bond, expressed in kJ/mol.
• Breaking bonds requires energy, while forming bonds releases energy.
• Breaking a C=O bond requires 799 kJ/mol, and breaking a C-H bond requires 411 kJ/mol.

Activation Energy

• Activation energy is the minimum energy to break reactant bonds and start a reaction.
• Released energy helps sustain the reaction once bonds are broken.

Exothermic Reaction

• Exothermic reactions break complex molecules into simpler ones.
• These release energy, and the products have less chemical potential energy.

Endothermic Reaction

• Endothermic reactions build complex molecules from simpler ones.
• Energy is absorbed, and the products have more chemical potential energy.

Spontaneous vs. Non-Spontaneous Changes

• Spontaneous processes occur independently after being started, like burning a match.
• Non-spontaneous processes require continuous energy input, such as boiling water.
• A reaction that releases energy (ΔG < 0) is spontaneous.
• A reaction that absorbs energy (ΔG > 0) is non-spontaneous.

Coupled Reactions

• Exergonic reactions release free energy that drives endergonic reactions, which absorb free energy.
• Catabolic reactions provide energy for anabolic reactions.

Endergonic & Exergonic Reactions

• Exergonic reactions release work energy, are spontaneous, and have a negative ΔG.
• Endergonic reactions absorb work energy, are non-spontaneous, and have a positive ΔG.

ATP - The Energy Currency of the Cell

• ATP (Adenosine Triphosphate) is the main energy carrier in cells.

Structure of ATP

• ATP consists of adenosine (adenine + ribose) and three phosphate groups.

How ATP Works

• ATP stores energy in its high-energy phosphate bonds.
• Breaking the last phosphate bond releases energy, converting ATP into ADP (Adenosine Diphosphate) and inorganic phosphate (Pi).
• ATP is recycled by reattaching a phosphate group to ADP through cellular respiration.

Types of Work Powered by ATP

• Mechanical work includes muscle contraction and chromosome movement.
• Transport work involves pumping substances across membranes, like the sodium-potassium pump.
• Chemical work drives non-spontaneous reactions like DNA replication.

Redox Reactions (Oxidation & Reduction)

• Oxidation occurs when a substance loses electrons.
• Reduction occurs when a substance gains electrons, reducing its positive charge.
• Energy released from redox reactions synthesizes ATP.

ATP Cycle & Regeneration

• ATP is constantly broken down to release energy and rebuilt from ADP + Pi.
• ATP synthase (enzyme) helps convert ADP to ATP in the mitochondria.
• Energy for ATP regeneration comes from catabolic reactions, such as the breakdown of food.
• ATP is produced in cellular respiration and photosynthesis.
• The electron transport chain creates a proton gradient to drive ATP synthase.
• Phosphorylation is when ATP transfers a phosphate to another molecule to power reactions.
• ATP powers processes like muscle contraction, active transport, and protein synthesis.
• ATP is continually recycled for energy needs.

Glycolysis

• Glycolysis breaks down glucose into two pyruvate molecules without requiring oxygen.
• Glycolysis yields a net of 2 ATP, 2 NADH, and 2 pyruvate molecules.
• Glycolysis has two phases: energy investment and energy-yielding.

Major Classes of Enzymes

• Transferases catalyze the transfer of functional groups from one molecule to another (e.g., kinases transfer phosphate groups).
• Oxidoreductases catalyze oxidation-reduction reactions (e.g., dehydrogenases remove hydrogen and transfer electrons).
• Isomerases rearrange atoms within a molecule to form an isomer (e.g., mutases shift functional groups within a molecule).
• Lyases break chemical bonds (C-C, C-O, C-N, etc.) without hydrolysis or oxidation (e.g., aldolase and enolase).
• Hydrolases break bonds using water in hydrolysis reactions (e.g., phosphatases remove phosphate groups).
• Ligases join two molecules together using ATP (e.g., DNA ligases join DNA fragments).

Steps of Glycolysis

• Step 1: Glucose is phosphorylated using ATP, forming Glucose-6-phosphate (G6P), trapping glucose inside the cell.
• Step 2: Glucose-6-phosphate is converted to Fructose-6-phosphate (F6P), preparing it for further phosphorylation.
• Step 3: ATP converts Fructose-6-phosphate into Fructose-1,6-bisphosphate (F1,6BP); this is the rate-limiting step.
• Step 4: Fructose-1,6-bisphosphate is split into two 3-carbon molecules: Glyceraldehyde-3-phosphate (G3P) and Dihydroxyacetone phosphate (DHAP).
• Step 5: DHAP is converted into another Glyceraldehyde-3-phosphate (G3P).
• Step 6: G3P is oxidized, and inorganic phosphate (Pi) is added, forming 1,3-Bisphosphoglycerate (1,3-BPG); NAD+ is reduced to NADH.
• Step 7: A phosphate from 1,3-BPG is transferred to ADP, forming ATP and 3-Phosphoglycerate (3PG); this is substrate-level phosphorylation.
• Step 8: 3-Phosphoglycerate is rearranged to 2-Phosphoglycerate (2PG).
• Step 9: 2-Phosphoglycerate is converted into Phosphoenolpyruvate (PEP) by removing water.
• Step 10: PEP transfers its phosphate to ADP, forming ATP, and Pyruvate.

Final Products of Glycolysis

• The final products per glucose molecule are 2 Pyruvate, 2 ATP (net gain) (4 ATP produced - 2 ATP used), and 2 NADH.

General Cellular Respiration Notes

• Cellular respiration generates ATP by breaking down glucose.
• Aerobic respiration requires oxygen, while anaerobic respiration does not.
• The overall reaction is C6H12O6 + 6O2 → 6CO2 + 6H2O + energy (ATP).
• The overall reaction consists of catabolic pathways that break down molecules to release energy.

Four Stages of Aerobic Respiration

• Stage 1: Glycolysis occurs in the cytosol, producing 2 ATP, 2 NADH, and 2 pyruvate molecules.
• Stage 2: Pyruvate Oxidation occurs in the mitochondrial matrix, producing 2 NADH and converting pyruvate into Acetyl-CoA.
• Stage 3: Krebs Cycle (Citric Acid Cycle) takes place in the mitochondrial matrix, producing 6 NADH, 2 FADH2, and 2 ATP.
• Stage 4: Electron Transport Chain & Chemiosmosis are located in the inner mitochondrial membrane, generating 32 ATP from NADH and FADH2.

Pyruvate Oxidation

• Pyruvate Oxidation occurs in the mitochondrial matrix.

Pyruvate Oxidation Process

• Decarboxylation is when a CO2 molecule is removed from pyruvate.
• Reduction of NAD+ occurs when NAD+ gains hydrogen atoms to form NADH.
• Formation of Acetyl-CoA is done when Coenzyme A (CoA) attaches to the remaining acetyl group.

Products of Pyruvate Oxidation (per glucose molecule)

• 2 CO2 molecules
• 2 NADH molecules
• 2 Acetyl-CoA molecules

Krebs Cycle (Citric Acid Cycle)

• Acetyl-CoA enters the cycle by combining with oxaloacetate to form citrate.
• This cycle uses 8 steps in total, and it begins & ends with the same compound (oxaloacetate).

Major Enzymes Involved in the Krebs Cycle

• Citrate Synthase converts Acetyl-CoA + Oxaloacetate into Citrate.
• Isocitrate Dehydrogenase produces NADH & CO2.
• α-Ketoglutarate Dehydrogenase produces NADH & CO2.
• Succinate Dehydrogenase produces FADH2.
• Malate Dehydrogenase produces NADH.

Products of Krebs Cycle (per glucose molecule, 2 turns of the cycle)

• 6 NADH molecules
• 2 FADH2 molecules
• 2 ATP molecules
• 4 CO2 molecules

Total ATP Yield from Glycolysis to Krebs Cycle

• After Glycolysis, Pyruvate Oxidation, & the Krebs Cycle, there are 4 ATP molecules.
• 10 NAHD molecules are used later in Electron Transport Chain.
• 2 FADH2 molecules
• 6 CO2 molecules (released as waste)

The Electron Transport Chain

• The ETC occurs in the inner mitochondrial membrane (cristae).
• It uses NADH & FADH2 from previous metabolic processes to generate ATP.
• Electrons move through 4 protein complexes & 2 mobile carriers.
• Oxygen (O2) is the final electron acceptor, forming H2O.
• H+ ions (protons) are pumped into the intermembrane.

ETC Components

• Complex I (NADH dehydrogenase) transfers electrons from NADH and pumps H+ out of the matrix.
• Complex II (Succinate dehydrogenase) transfers electrons from FADH2 to ubiquinone (UQ), which moves them to Complex III.
• Complex III (Cytochrome complex) transfers electrons from UQ, and cytochrome c moves electrons to Complex IV.
• Complex IV (Cytochrome oxidase) transfers electrons from cytochrome C.
• O2 accepts electrons & combines with H+ to form H2O.

Chemiosmosis & ATP Production

• A H+ gradient (proton-motive force) powers ATP synthesis.
• ATP synthase uses H+ movement to convert ADP + Pi → ATP.

Uncoupling & Alternative Pathways

• Uncoupling proteins allow H+ to bypass ATP synthase, generating heat instead of ATP.

ATP Yield

• NADH yields 3 ATP (passes through 3 hydrogen pumps).
• FADH2 yields 2 ATP (passes through 2 hydrogen pumps).
• The total net ATP yield is 38 ATP (ideal value).
• The actual ATP yield is 30-32 ATP (due to losses).

Eukaryotes vs. Prokaryotes

• Some ATP is lost in eukaryotes because hydrogen ions leak through the inner mitochondrial membrane.
• Energy is used to transport pyruvate into mitochondria.
• Energy is used to move ATP into the cytoplasm for use.
• Prokaryotes can make 38 ATP because they don't lose ATP transporting NADH across membranes.

Metabolic Pathway Connections

• Pathways are not closed; nutrients can enter at different stages.
• Dietary nutrients are broken down into intermediates used in glycolysis & the Krebs cycle.

Regulation of Cellular Respiration

• Phosphofructokinase (Glycolysis) is inhibited by excess ATP or citrate and activated by ADP.
• Pyruvate dehydrogenase (Pyruvate Oxidation) is inhibited by excess NADH.

Anaerobic Respiration & Fermentation

• Anaerobic Respiration is a metabolic process where an inorganic molecule (e.g., sulfate, nitrate, carbon dioxide) is used as the final electron acceptor instead of oxygen.
• Some bacteria (like E. coli) use nitrate as the final electron acceptor.
• Methanogens (found in swamps & the guts of ruminants) use carbon dioxide as the final electron acceptor.

Fermentation

• Fermentation is a metabolic pathway that regenerates NAD+ from NADH by transferring electrons to an organic acceptor molecule (instead of using an electron transport chain).
• Fermentation produces only ATP generated during glycolysis.

Types of Fermentation

• Lactate Fermentation (in muscle cells & some single-celled organisms) converts pyruvate to lactate, oxidizing NADH to NAD+.
• Lactate lowers pH & makes the medium acidic.
• Oxygen is needed to metabolize lactate in animals, leading to oxygen debt.
• Alcohol Fermentation occurs in yeast & some bacteria.
• Pyruvate is converted to ethanol & carbon dioxide in Alcohol Fermentation.
• Organisms performing Alcohol Fermentation are called facultative anaerobes (can switch between aerobic & anaerobic respiration).
• Alcohol Fermentation is used in making bread, wine, & beer.