Energy, Chemical Reactions, and Cellular Respiration Study Notes

Overview of Energy and Metabolism

• Definition of Energy: Energy is defined as the capacity to do work.
• Necessity of Energy: All living organisms require energy to perform essential life functions including:
  • Powering muscle contraction.
  • Pumping blood throughout the body.
  • Absorbing nutrients.
  • Exchanging respiratory gases.
  • Synthesizing new molecules.
  • Establishing cellular ion concentrations.
• Energy Currency: Glucose is broken down through metabolic pathways to form Adenosine Triphosphate (ATP), which serves as the "energy currency" of cells.

Classes and Forms of Energy

• Classes of Energy:
  • Potential Energy: Energy of position or stored energy.
  • Kinetic Energy: Energy of motion.
  • Conversion: Both classes can be converted from one to the other. Potential energy must be converted to kinetic energy before it can do work.
• Energy in Cellular Structures:
  • Plasma Membrane: A concentration gradient exists across the plasma membrane, serving as a boundary between the inside and outside of the cell; this represents potential energy.
  • Electron Shells: Electrons move from a higher-energy shell to a lower-energy shell. As they fall, kinetic energy is released and can be harnessed to do work.
• Forms of Potential Energy:
  • Chemical Energy: The most significant form of potential energy in the body. It is stored in a molecule’s chemical bonds and released when those bonds are broken.
  • Storage Molecules: Primary molecules for chemical energy storage include triglycerides, glucose, and ATP.
• Forms of Kinetic Energy:
  • Electrical Energy: The movement of charged particles. A biological example is the movement of ions across the plasma membrane of a neuron.
  • Mechanical Energy: Objects in motion due to an applied force, such as muscle contraction for walking.
  • Sound Energy: Compression of molecules caused by a vibrating object, such as sound waves vibrating the eardrum.
  • Radiant Energy: The energy of electromagnetic waves. A primary example is visible light striking the retina.
  • Heat: Kinetic energy associated with the random movement of atoms, ions, or molecules. It is typically not available to do work and is measured as the temperature of a substance.

The Electromagnetic Spectrum

• Wavelength and Frequency: The spectrum ranges from high frequency/short wavelength to low frequency/long wavelength.
• Segments of the Spectrum:
  • Gamma Rays: Approximately $0.001\,nm$ to $1\,nm$.
  • X-rays: $1\,nm$ to $10\,nm$.
  • UV Light: $10\,nm$ to $400\,nm$.
  • Visible Light: Perceived by the retina; ranges from $400\,nm$ to $740\,nm$.
  • Infrared Light: $740\,nm$ to $0.01\,cm$.
  • Microwaves: $0.01\,cm$ to $1\,m$.
  • Radio Waves: $1\,m$ to $100\,m$.
• Biological Impact: High-energy ranges (Gamma, X-rays, UV) are capable of entering the body and damaging DNA, leading to mutations.

Laws of Thermodynamics

• Thermodynamics: The study of energy transformations.
• First Law of Thermodynamics: Energy can neither be created nor destroyed; it can only change in form.
• Second Law of Thermodynamics: When energy is transformed, some energy is lost as heat. Consequently, the amount of usable energy decreases.
  • Example: Moving around to warm up on a cold day converts chemical energy to mechanical energy, with heat as a byproduct.

Chemical Equations and Metabolism

• Metabolism: The sum of all biochemical reactions in living organisms.
• Chemical Reactions: These occur when chemical bonds in existing molecular structures are broken and new bonds are formed.
• Components of an Equation:
  • Reactants: Substances present prior to the start of the reaction (written on the left side).
  • Products: Substances formed by the reaction (written on the right side).
  • Balance: In a balanced equation, the number of elements must be equal on both sides.

Classification of Chemical Reactions

Based on Chemical Structure

• Decomposition Reaction: An initial large molecule is broken down into smaller structures ($AB \rightarrow A + B$). In the body, these are collectively called Catabolism (catabolic reactions).
  • Example: Hydrolysis of sucrose into glucose and fructose.
• Synthesis Reaction: Two or more structures combine to form a larger structure ($A + B \rightarrow AB$). In the body, these are collectively called Anabolism (anabolic reactions).
  • Example: Dehydration synthesis forming a dipeptide.
• Exchange Reaction: Groups are exchanged between two chemical structures, involving both decomposition and synthesis ($AB + C \rightarrow A + BC$). These are the most prevalent reactions in the human body.
  • Example: Production of ATP in muscle tissue.

Based on Chemical Energy

• Exergonic Reactions: Reactants contain more bond energy than products; energy is released, resulting in a net decrease in potential energy. (e.g., Decomposition).
• Endergonic Reactions: Reactants contain less bond energy than products; energy must be supplied, resulting in a net increase in potential energy. (e.g., Synthesis).

Oxidation-Reduction (Redox) Reactions

• Oxidation: A structure loses an electron.
• Reduction: A structure gains an electron.
• Coupling: These reactions always occur together. Electrons may move alone or with a hydrogen ion.
• Example: NAD+: Energy-rich molecules like glucose are oxidized, giving up two hydrogen atoms. Nicotinamide Adenine Dinucleotide ($NAD^+$) is reduced to $NADH$ by gaining a hydrogen ion and two electrons.

ATP Cycling and Reversibility

• ATP Cycling: A continuous cycle of forming and splitting ATP.
  • ATP Formation: Endergonic reaction. Energy from oxidized food molecules is used to bond ADP and a free phosphate group ($P_i$).
  • ATP Splitting (Hydrolysis): Exergonic reaction. Energy released from breaking the high-energy bond is used for cellular processes.
  • Availability: Only a few seconds' worth of ATP is present at any time; formation occurs continuously.
• Reaction Reversibility:
  • Irreversible Reaction: Net loss of reactants and net gain of products.
  • Reversible Reaction: Proceeds in both directions. At Equilibrium, there is no net change in the concentration of reactants or products.
  • The Carbonic Acid Reaction:       $\text{CO}_2 + \text{H}_2\text{O} \rightleftharpoons \text{H}_2\text{CO}_3 \rightleftharpoons \text{HCO}_3^- + \text{H}^+$       The unstable carbonic acid dissociates into bicarbonate and hydrogen ions.

Reaction Rates and Activation Energy

• Reaction Rate: A measure of how quickly a chemical reaction occurs.
• Activation Energy ($E_a$): The energy required to break existing chemical bonds to initiate a reaction.
• Inhibiting Factors: In biological systems, increasing temperature to overcome $E_a$ is dangerous as it would denature proteins. Instead, cells use Enzymes.

Enzyme Function and Mechanism

• Enzymes as Catalysts: Biologically active catalysts that accelerate reactions by decreasing activation energy. They only facilitate reactions that would already occur.
• Structure: Enzymes are typically globular proteins ranging from $60$ to $2500$ amino acids.
  • Active Site: A unique 3D structure that provides specificity, permitting only a specific substrate to bind.
• Mechanism of Action:
  1. Substrate enters the active site.
  2. An Enzyme-Substrate Complex forms.
  3. Induced Fit Model: The enzyme changes shape slightly for a closer fit.
  4. Shape change stresses bonds, facilitating the reaction.
  5. Products are released and the enzyme returns to its original form.
• Cofactors: Nonprotein "helpers" required for enzyme activity.
  • Inorganic Cofactors: Ions such as Zinc ($Zn^{2+}$).
  • Organic Cofactors: Called Coenzymes (e.g., vitamins).

Enzyme Classification and Naming

Functional Classes

1. Oxidoreductases: Facilitate redox reactions (e.g., Dehydrogenases).
2. Transferases: Transfer atoms/molecules between structures (e.g., Kinases transfer phosphate groups).
3. Hydrolases: Split bonds using water.
4. Isomerases: Convert one isomer to another.
5. Ligases: Bond two molecules together.
6. Lyases: Split bonds without using water.

Naming Conventions

• Typically based on the substrate or product, subclass, and the suffix -ase.
• Examples:
  • Pyruvate dehydrogenase: Transfers hydrogen from pyruvate.
  • DNA polymerase: Helps form DNA.
  • Lactase: Digests lactose.

Factors Affecting Reaction Rates

• Concentration: Increasing enzyme or substrate concentration accelerates the rate up to the Point of Saturation (all enzyme molecules are occupied).
• Temperature:
  • Optimum Temperature: For human enzymes, approximately $40^\circ\text{C}$ ($104^\circ\text{F}$).
  • Moderate Fever: Enhances enzyme activity.
  • Severe Temperature Increase: Causes denaturation and loss of function.
• pH:
  • Optimum pH: Usually between $6$ and $8$ for most human enzymes.
  • Exceptions: Enzymes in the stomach function at a much lower pH.
  • Effect: Changes in pH disrupt electrostatic interactions, causing denaturation.

Control of Enzyme Activity

• Inhibitors: Substances that bind to enzymes and turn them off to prevent overproduction.
  • Competitive Inhibitors: Resemble the substrate and compete for the active site. Influenced by substrate concentration.
  • Noncompetitive (Allosteric) Inhibitors: Bind to an Allosteric Site (not the active site), inducing a conformational change. They are not influenced by substrate concentration.
• Metabolic Pathways: A series of enzymes where the product of one becomes the substrate for the next.
• Multienzyme Complexes: Groups of attached enzymes working in sequence (e.g., pyruvate dehydrogenase).
  • Advantages: Prevents diffusion of intermediates and allows for easier regulation.
• Regulation Mechanisms:
  • Negative Feedback: The end product of a pathway acts as an allosteric inhibitor to an enzyme early in the pathway.
  • Phosphorylation: Addition of a phosphate group by kinases/phosphorylases; can activate or deactivate enzymes.
  • Dephosphorylation: Removal of a phosphate group by phosphatases.

Cellular Respiration: Overview of Glucose Oxidation

• General Definition: An exergonic multistep metabolic pathway where organic molecules are oxidized to synthesize ATP.
• Requirement: Oxygen is required for maximum ATP production.
• Net Equation:     $\text{C}_6\text{H}_{12}\text{O}_6 + 6\text{O}_2 \rightarrow 6\text{CO}_2 + 6\text{H}_2\text{O} + \text{Energy}$
• Methods of ATP Production:
  • Substrate-level Phosphorylation: Direct transfer of phosphate to ADP (least common).
  • Oxidative Phosphorylation: Energy first released to coenzymes ($NADH, FADH_2$), then transferred to form ATP via the Electron Transport System (most common).
• Locations: Cytosol and Mitochondria.

The Four Stages of Glucose Oxidation

1. Glycolysis

• Location: Cytosol.
• Oxygen Requirement: Anaerobic (No oxygen required).
• Process: Ten enzymes participate.
• Investment Phase (Steps 1–5): Glucose ($6C$) is split into two molecules of Glyceraldehyde 3-phosphate (G3P). Two ATP are invested.
• Harvesting Phase (Steps 6–10): Occurs twice per glucose.
  • Step 6: $P_i$ added, $NADH$ formed.
  • Step 7: ATP formed.
  • Step 10: ATP and Pyruvate formed.
• Yield: Net $2\,ATP$, $2\,NADH$, and $2\,Pyruvate$.
• Regulation: Phosphofructokinase (PFK) is the key regulatory enzyme; it is inhibited by high ATP levels.

2. Intermediate Stage

• Location: Mitochondrial Matrix.
• Oxygen Requirement: Aerobic (Requires oxygen).
• Enzyme: Pyruvate dehydrogenase complex.
• Process: Pyruvate combined with Coenzyme A (CoA) to form Acetyl CoA.
• Byproducts: One carbon is released as $CO_2$ (decarboxylation) and one $NADH$ is produced per pyruvate.
• Total Yield (per glucose): $2\,NADH$, $2\,Acetyl\,CoA$, $2\,CO_2$.

3. Citric Acid Cycle (Krebs Cycle)

• Location: Mitochondrial Matrix.
• Oxygen Requirement: Aerobic.
• Steps:
  1. Acetyl CoA + Oxaloacetate $\rightarrow$ Citrate + CoA.
  2. Isomerization into Isocitrate.
  3. Decarboxylation and $NADH$ formation $\rightarrow$ Alpha-ketoglutarate.
  4. Decarboxylation and $NADH$ formation $\rightarrow$ Succinyl CoA.
  5. Removal of CoA and ATP formation $\rightarrow$ Succinate.
  6. Hydrogen transfer to form $FADH_2$ $\rightarrow$ Fumarate.
  7. Addition of water $\rightarrow$ Malate.
  8. Dehydrogenation to form $NADH$ $\rightarrow$ Oxaloacetate (regenerated).
• Yield per cycle (one turn): $1\,ATP$, $3\,NADH$, $1\,FADH_2$, $2\,CO_2$.
• Yield per glucose (two turns): $2\,ATP$, $6\,NADH$, $2\,FADH_2$, $4\,CO_2$.

4. Electron Transport System (ETS)

• Location: Mitochondrial Cristae (inner membrane).
• Components: $H^+$ pumps and electron carriers (Electron Transport Chain).
• Process:
  1. Transfer: Electrons from $NADH$ and $FADH_2$ are passed through carriers to Oxygen ($O_2$), the final electron acceptor.
  2. Water Formation: $O_2 + 4e^- + 4H^+ \rightarrow 2H_2O$.
  3. Proton Gradient: Kinetic energy of "falling" electrons is used by pumps to move $H^+$ from the matrix to the outer compartment, creating a gradient.
  4. Chemiosmosis: $H^+$ flows down its gradient back into the matrix through ATP Synthase. This kinetic energy drives the bond between ADP and $P_i$.
• ATP Yield:
  • Electrons from $NADH$ (entering at the first pump) generate $3\,ATP$.
  • Electrons from $FADH_2$ (entering at the second pump) generate $2\,ATP$.

Summary of ATP Production (Per Glucose Molecule)

• Net ATP: While the theoretical total is $38\,ATP$, some energy is used during the process, resulting in a Net Yield of 30 ATP.

Alternative Fates and Fuel Molecules

• Pyruvate with Insufficient Oxygen:
  • The Electron Transport Chain slows down; $NADH$ and $FADH_2$ accumulate.
  • To continue glycolysis, $NAD^+$ must be regenerated.
  • Lactate Dehydrogenase converts Pyruvate to Lactate (Lactic Acid), oxidizing $NADH$ back to $NAD^+$.
  • This only generates a net of $2\,ATP$ per glucose.
• Other Fuels:
  • Fatty Acids: Undergo Beta Oxidation (removal of two carbons at a time) to form Acetyl CoA. Can only be oxidized aerobically (requires oxygen).
  • Amino Acids: Amine group is removed (Waste product $\rightarrow$ Urea) and the remaining structure enters at various points depending on the specific amino acid.

Clinical Views

• Drugs as Enzyme Inhibitors:
  • Penicillin: Targets bacterial enzymes to stop infection spread.
  • Pravastatin (Statins): Inhibits liver enzymes responsible for cholesterol synthesis to lower heart disease risk.
• Lactose Intolerance: Caused by a deficiency of the enzyme Lactase. Lactose cannot be broken down into glucose and galactose, leading to GI distress (nausea, gas, bloating). Treated with lactase supplements or milk avoidance.
• Cyanide Poisoning: Cyanide binds to an electron carrier in the ETS, inhibiting ATP production. Organs requiring high oxygen (heart, brain) are most affected.

Questions & Discussion

• Question 1: Movement of ions from high to low concentration and movement of electrons between shells are examples of which energy class?
  • Response: (b) Kinetic energy.
• Question 2: Muscle contraction is an example of what form of energy?
  • Response: Mechanical energy.
• Question 3: What happens to energy during transformation and what is generated?
  • Response: It changes form, and according to the second law, some energy is always lost as heat.
• Question 4: What are the differences between reactants and products?
  • Response: Reactants are present before the reaction (left side); products are the results of the reaction (right side).
• Question 5: For a reaction bonding simple structures into complex ones:
  • Response: (a) synthesis; (b) endergonic; (c) anabolism.
• Question 6: What molecule is the energy currency formed from glucose?
  • Response: ATP.
• Question 7: What happens when equilibrium is disturbed?
  • Response: Increasing reactants or decreasing products drives the reaction to the right; decreasing reactants or increasing products drives it to the left.
• Question 8: Effect of fever and risk of high fever?
  • Response: Moderate fever increases reaction rates and enzyme efficiency. High fever risks deactivating enzymes via protein denaturation.
• Question 9: Relationship between enzymes and activation energy?
  • Response: Enzymes lower the activation energy required to start a reaction.
• Question 10: What is the active site and its relation to the substrate?
  • Response: The active site is a uniquely shaped pocket in the enzyme where a specific substrate binds like a key in a lock.
• Question 11: Mechanism of action and role of cofactors?
  • Response: Formation of enzyme-substrate complex, induced fit, bond stress/formation, and product release. Cofactors are inorganic ions or organic coenzymes assisting the reaction.
• Question 12: How are enzymes named?
  • Response: Based on the substrate/product plus the suffix "-ase" (e.g., lactase for lactose).
• Question 13: Factors affecting enzyme rates?
  • Response: Rates increase with concentration until saturation. Optimal temperature and pH are required; extremes cause denaturation.
• Question 14: Competitive vs. noncompetitive inhibition?
  • Response: Competitive binds the active site; noncompetitive binds an allosteric site to change the enzyme's shape.
• Question 15: Metabolic pathway and negative feedback?
  • Response: A sequence of enzyme-catalyzed reactions. Negative feedback uses the end product to inhibit an early enzyme, maintaining homeostasis of product levels.
• Question 16: Two phosphate processes in regulation?
  • Response: Phosphorylation and dephosphorylation.
• Question 17: Process of glucose oxidation?
  • Response: A series of exergonic steps breaking bonds in glucose to release energy used to synthesize ATP.
• Question 18: Four stages of cellular respiration and locations?
  • Response: 1. Glycolysis (cytosol); 2. Intermediate (mitochondria); 3. Citric Acid Cycle (mitochondria); 4. ETS (mitochondria/cristae).
• Question 19: Describe Glycolysis.
  • Response: Cytosol, anaerobic. Net: $2\,ATP$, $2\,NADH$, and $2\,Pyruvate$.
• Question 20: Two fates of pyruvate?
  • Response: Enters mitochondria for aerobic respiration (if $O_2$ is sufficient) or stays in cytosol to form lactate (if $O_2$ is insufficient).
• Question 21: Intermediate stage reaction?
  • Response: Aerobic. Catalyzed by pyruvate dehydrogenase. Pyruvate + CoA $\rightarrow$ Acetyl CoA + $CO_2$ + $NADH$.
• Question 22: Citric acid cycle summary?
  • Response: Aerobic process in the matrix. Acetyl CoA is substrate; yields $ATP, NADH, FADH_2, CO_2$; regenerates oxaloacetate.
• Question 23: Energy molecules per step?
  • Response: Glycolysis ($ATP, NADH$), Intermediate ($NADH$), Citric Acid ($ATP, NADH, FADH_2$).
• Question 24: Importance of NADH and FADH2?
  • Response: They serve as electron/hydrogen carriers that deliver energy to the Electron Transport System for oxidative phosphorylation.
• Question 25: Three steps of ETS?
  • Response: 1. Electron transfer and oxidation of coenzymes; 2. Establishment of proton gradient via $H^+$ pumps; 3. Harnessing gradient via ATP synthase to form ATP.
• Question 26: Net ATP molecules?
  • Response: 2 net ATP from glycolysis (without mitochondria); 30 net ATP total including mitochondria.
• Question 27: Pyruvate with insufficient oxygen?
  • Response: Converted to lactate. This regenerates $NAD^+$ to keep glycolysis running.
• Question 28: Why is oxygen required to burn fatty acids?
  • Response: Fatty acids produce Acetyl CoA via beta oxidation, and Acetyl CoA enters the aerobic citric acid cycle; the regeneration of carriers required for this depends on the ETS, which requires oxygen as the final acceptor.