Bio 101 Unit 2 Exam Knowledge Check Ultimate Study Guide

Energy and Bioenergetics

• Energy is defined as the ability to do work or bring about a change. All living organisms require a constant supply of energy to maintain structural organization, grow, develop, metabolize, and reproduce.

• The majority of life on Earth is ultimately dependent on solar energy. Photosynthesizers (producers such as plants, algae, and cyanobacteria) capture solar energy to synthesize organic nutrients, which directly or indirectly provide energy to consumers.

• Energy exists in two primary forms:

  • Kinetic Energy: The energy of motion. Examples include water flowing over a waterfall, a ball rolling down a hill, or a moose walking through grass.

  • Potential Energy: Stored energy whose capacity to accomplish work is not currently being utilized. Food possesses potential energy because the energy stored within its chemical bonds can be converted into kinetic energy.

  • Chemical Energy: A specific form of potential energy present in organic biomolecules, such as carbohydrates, proteins, and lipids.

  • Mechanical Energy: A form of kinetic energy that results when chemical energy is converted into motion, such as the muscular movement of a walking organism.

Laws of Thermodynamics and Entropy

• Bioenergetics is governed by two fundamental laws of thermodynamics that explain how energy flows through cells and ecosystems:

• First Law of Thermodynamics (Law of Conservation of Energy): Energy cannot be created or destroyed, but it can be converted from one form to another.

  • Plants do not create energy; they capture solar energy and convert it into the chemical energy stored in carbohydrate bonds.

  • As an animal uses stored potential energy to power its muscles, no energy is destroyed; rather, chemical energy is transformed into mechanical energy and heat.

• Second Law of Thermodynamics: Energy cannot be changed from one form to another without a loss of usable energy.

  • During every energy transformation, a substantial amount of energy is released into the environment as nonusable heat.

  • Because dissipated heat cannot be recaptured to perform cellular work, no energy conversion process is $100\%$ efficient.

  • Automobiles convert gasoline chemical energy into mechanical energy with an efficiency of $20\%$ to $30\%$. Biological cells convert chemical energy into ATP with an efficiency of approximately $40\%$, with the remaining $60\%$ dissipated as heat.

• Entropy ($S$): The measure of randomness or disorganization in a system.

  • The second law dictates that every natural energy transformation increases the total entropy of the universe, moving systems toward greater disorder.

  • Organized structures are less stable and have high potential energy; disorganized structures are more stable and have low potential energy.

  • Glucose ($\text{C}_6\text{H}_{12}\text{O}_6$) is highly organized, structured, and less stable; over time, it naturally breaks down into energy-poor, less organized, and highly stable carbon dioxide ($\text{CO}_2$) and water ($\text{H}_2\text{O}$).

  • Hydrogen ions ($\text{H}^+$) accumulated on one side of a membrane represent an organized state with high potential energy. Allowing them to randomly distribute across the membrane increases entropy.

  • Living organisms serve as temporary repositories of structural order maintained only through the constant input of energy from the sun.

Free Energy, Exergonic, and Endergonic Reactions

• Free Energy ($\Delta G$): The amount of energy remaining available to do work after a chemical reaction has taken place.

• Free energy change is calculated by subtracting the free energy content of reactants from that of products:   $\Delta G = G_{\text{products}} - G_{\text{reactants}}$

• Exergonic Reactions: Spontaneous chemical reactions that release energy. The products contain less free energy than the reactants, resulting in a negative change in free energy ($-\Delta G$).

• Endergonic Reactions: Nonspontaneous reactions that require an input of energy to proceed. The products contain more free energy than the reactants, resulting in a positive change in free energy ($+\Delta G$).

• Metabolic processes blend both reaction types. Endergonic macromolecule synthesis (e.g., protein and carbohydrate synthesis) is driven forward by coupling with exergonic reactions.

Structure and Role of ATP

• Adenosine Triphosphate (ATP): Known as the energy currency of the cell. It serves as an intermediate energy carrier that transfers energy from exergonic metabolic reactions to endergonic reactions.

• Chemical Structure of ATP: Composed of three distinct chemical units:

  • The nitrogenous base adenine.

  • The $5$-carbon sugar ribose (adenine + ribose together form adenosine).

  • Three negatively charged phosphate groups attached in sequence.

• Mechanism of Energy Release: The three phosphate groups carry negative charges and strongly repel one another, creating inherent instability and high potential energy.

• Removal of the terminal phosphate group via hydrolysis breaks the unstable bond, releasing energy:   $\text{ATP} + \text{H}_2\text{O} \rightarrow \text{ADP} + \text{P}_i + \text{energy}$

• Hydrolysis of $1\,\text{mole}$ of ATP under standard cellular conditions yields approximately $7.3\,\text{kcal/mol}$ of free energy.

• ADP Stability vs. ATP Potential Energy: Adenosine Diphosphate (ADP) and inorganic phosphate ($\text{P}_i$) are structurally more stable and possess significantly lower potential energy than ATP.

Coupled Reactions and Cellular Work

• Coupled Reactions: Reactions where an energetically favorable exergonic reaction (such as ATP hydrolysis) is linked directly to an energetically unfavorable endergonic reaction, allowing both to occur simultaneously at the same site.

• Free energy released by ATP hydrolysis exceeds the free energy demanded by the endergonic process, making the overall coupled reaction exergonic ($-\Delta G$).

• Mechanisms of Coupling: ATP breakdown is coupled to reactions via two primary methods:

  1. Energizing a Reactant: A phosphate group is enzymatically transferred from ATP directly to a reactant, creating a phosphorylated intermediate with higher potential energy.

  2. Changing Molecular Shape: Transfer of a phosphate group to a protein causes a conformational shape change.

• Examples of ATP-Driven Cellular Work:

  • Chemical Work: Provides energy needed to synthesize cellular macromolecules (anabolism).

  • Transport Work: Provides energy to active transport carrier proteins. Hydrolysis of ATP transfers a phosphate to a transport protein, altering its shape so it can pump polar ions or molecules across nonpolar plasma membranes.

  • Mechanical Work: Powers organelle movements, flagellar/ciliary beating, chromosome movement, and muscle contraction.

  • Muscle Contraction Detail: Myosin heads bind ATP in a resting shape. ATP hydrolyzes into ADP and $\text{P}_i$, changing myosin's shape so it can attach to an actin filament. Releasing ADP and $\text{P}_i$ causes myosin to pull the actin filament, converting chemical energy directly into mechanical energy.

• The ATP Cycle: Cells do not store vast reserves of ATP. Instead, ATP is continuously regenerated from ADP and $\text{P}_i$ using free energy derived from the breakdown of glucose during cellular respiration.

Enzymes and Biological Catalysts

• Enzymes: Organic biological catalysts (predominantly proteins, though some are catalytic RNA molecules called ribozymes) that dramatically accelerate chemical reaction rates without being consumed or permanently altered.

• Ribozymes specifically catalyze RNA synthesis and protein synthesis at ribosomes.

• Metabolic Pathways: Structured series of consecutive, linked enzymatic reactions. Pathways begin with a specific reactant and proceed through intermediates to yield a final product:   $\text{A} \xrightarrow{\text{E}_1} \text{B} \xrightarrow{\text{E}_2} \text{C} \xrightarrow{\text{E}_3} \text{D}$

  • Substrates for the first reaction are converted into products, which then serve as substrates for the next enzyme.

  • Specificity of individual enzymes prevents wasteful side reactions and allows precise control over metabolic pathways.

• Activation Energy ($E_a$): The initial input of energy required to destabilize chemical bonds and initiate a reaction.

  • Activation energy prevents complex organic molecules from degrading spontaneously.

  • Enzyme Action: Enzymes speed reaction rates (frequently by more than $10\,\text{million}$ times) specifically by lowering the energy of activation ($E_a$).

  • Enzymes do not alter the overall free energy content ($\Delta G$) or final ratio of products to reactants.

• Active Site and Induced Fit Model:

  • Active Site: A restricted region on the enzyme that directly binds the substrate(s).

  • Induced Fit Model: The enzyme's active site undergoes a flexible structural change upon substrate binding to achieve an optimal fit, facilitating bond breaking or forming. Once products are released, the active site returns to its original configuration.

Factors Affecting Enzyme Activity

• Substrate Concentration: Reaction rates increase as substrate concentration rises due to more frequent collisions between substrate molecules and active sites. When all active sites are continuously occupied, the enzyme reaches its maximum reaction rate ($V_{\max}$).

• Enzyme Concentration: Increasing the concentration of active enzyme increases the overall catalytic rate, provided substrate is abundant.

• Temperature:

  • As temperature increases, substrate and enzyme molecules gain kinetic energy, causing more frequent and energetic collisions, which increases reaction rate.

  • Beyond an optimal temperature, thermal agitation breaks hydrogen bonds holding the enzyme's tertiary structure, causing denaturation (loss of $3\text{D}$ shape and function).

  • Biological Significance: Warm-blooded mammals maintain elevated internal body temperatures to optimize enzyme catalytic rates. Warm-spring prokaryotes possess specialized enzymes that withstand extreme heat without denaturing. Siamese cat coat patterns result from a mutated enzyme that is active only at cooler peripheral body locations (ears, face, feet, tail), depositing dark pigment there.

• pH:

  • Each enzyme exhibits maximum activity at a specific optimal pH.

  • Pepsin (stomach enzyme) functions optimally at an acidic pH of approximately $2.0$

  • Trypsin (pancreatic enzyme in intestine) functions optimally at a basic pH of approximately $8.0$

  • Deviations from optimal pH alter R-group ionization, disrupting hydrogen and ionic bonds, denaturing the enzyme.

Enzyme Cofactors, Coenzymes, and Activation

• Cofactors: Inorganic ions or nonprotein organic molecules required at the active site for proper enzyme function.

  • Inorganic Cofactors: Essential metallic ions such as copper ($\text{Cu}$), zinc ($\text{Zn}$), and iron ($\text{Fe}$).

  • Coenzymes: Organic, nonprotein cofactors that participate directly in reactions, often transferring atoms or electrons between substrates.

• Role of Vitamins: Vitamins are small organic dietary nutrients required in trace quantities that act as structural components of coenzymes.

  • Niacin: Structural constituent of the coenzyme $\text{NAD}^+$. Niacin deficiency causes the skin disorder pellagra.

  • Riboflavin (Vitamin $\text{B}_2$): Structural constituent of the coenzyme $\text{FAD}$. Riboflavin deficiency causes cracking at the corners of the mouth.

• Regulation of Enzyme Activation:

  • Genes can be turned on or off to adjust enzyme synthesis concentrations.

  • Inactive enzymes can be activated covalently by protein kinases (which add phosphate groups) or deactivated by phosphatases (which remove phosphate groups).

  • Activation may also occur via selective cleavage of peptide segments or association with secondary proteins/cofactors.

Enzyme Inhibition and Regulation

• Enzyme Inhibition: Occurs when a molecule (an inhibitor) binds to an enzyme and decreases its catalytic activity.

• Noncompetitive Inhibition and Feedback Control:

  • An inhibitor binds to a regulatory region distinct from the active site, known as the allosteric site.

  • Allosteric binding induces a conformational shape change in the active site, preventing substrate binding.

  • Feedback Inhibition (Negative Feedback): The end product of a metabolic pathway acts as an allosteric inhibitor on the first enzyme ($\text{E}_1$) of the pathway. When product levels are sufficient, the pathway is automatically shut down to conserve raw materials and energy.

• Competitive Inhibition: An inhibitor structurally resembles the substrate and competes directly for binding to the active site. Product forms only when the true substrate binds.

• Reversibility: Most physiological inhibition is reversible. Irreversible inhibition permanently destroys or inactivates the enzyme (e.g., carbon monoxide binding to respiratory enzymes).

Principles of Oxidation-Reduction (Redox) Reactions

• Redox Reactions: Paired chemical reactions involving the transfer of electrons from one atom or molecule to another.

• OIL RIG Mnemonic:

  • OIL: Oxidation Is Loss of electrons (or loss of hydrogen atoms).

  • RIG: Reduction Is Gain of electrons (or gain of hydrogen atoms).

• In organic biomolecules, a hydrogen atom consists of one proton and one electron ($\text{H}^+ + e^-$). Removal of hydrogen atoms represents oxidation, whereas addition of hydrogen atoms represents reduction.

• Oxidation and reduction always occur simultaneously because electrons lost by an oxidized molecule are immediately accepted by a reduced molecule.

Photosynthesis: Autotrophs and Leaf Structure

• Photosynthesis: The anabolic metabolic process by which autotrophs convert solar energy into the stored chemical energy of carbohydrates.

• Autotrophs: Self-feeding organisms (plants, algae, cyanobacteria) that synthesize organic compounds from inorganic raw materials. Green photosynthesizers generate between $100\,\text{billion}$ and $200\,\text{billion}$ metric tons of sugar annually.

• Heterotrophs: Organisms that cannot synthesize organic compounds from inorganic sources and must ingest preformed organic food.

• Anatomy of Photosynthetic Leaves in Flowering Plants:

  • Photosynthesis occurs primarily within the specialized mesophyll tissue of leaves.

  • Stomata (singular: Stoma): Microscopic pore openings on leaf surfaces that admit atmospheric carbon dioxide ($\text{CO}_2$).

  • Vascular Tissue (Leaf Veins): Transport water ($\text{H}_2\text{O}$) absorbed by roots up through stems into leaves.

  • Chloroplast Structure: Organelles surrounded by a double membrane system:

  • Stroma: Fluid-filled interior region surrounding grana; contains enzymes that reduce $\text{CO}_2$ to carbohydrates during the Calvin cycle.

  • Thylakoids: Flattened sac-like membranes containing embedded chlorophyll and accessory pigments. Site of light-dependent reactions.

  • Grana (singular: Granum): Stacks of thylakoid sacs.

  • Thylakoid Space: Fluid compartment enclosed within thylakoid membranes acting as an $\text{H}^+$ ion reservoir.

Overview and Stages of Photosynthesis

• Chemical Equation for Photosynthesis:   $6\,\text{CO}_2 + 12\,\text{H}_2\text{O} + \text{solar energy} \rightarrow \text{C}_6\text{H}_{12}\text{O}_6 + 6\,\text{H}_2\text{O} + 6\,\text{O}_2$   (Simplified: $6\,\text{CO}_2 + 6\,\text{H}_2\text{O} + \text{solar energy} \rightarrow \text{C}_6\text{H}_{12}\text{O}_6 + 6\,\text{O}_2$)

• Redox Breakdown: Carbon dioxide ($\text{CO}_2$) is reduced to carbohydrate ($\text{CH}_2\text{O}$ or glucose); water ($\text{H}_2\text{O}$) is oxidized to oxygen gas ($\text{O}_2$).

• Oxygen released into the atmosphere originates directly from water splitting, not from carbon dioxide.

• Photosynthesis consists of two distinct, interconnected stages:

  1. Light Reactions (Light-Dependent): Occur in thylakoid membranes in the presence of sunlight. Solar energy is captured by chlorophyll, energizing electrons that travel through an electron transport chain to generate ATP and NADPH. Water is split to release $\text{O}_2$

  2. Calvin Cycle Reactions (Light-Independent): Occur in the stroma. ATP and NADPH produced in light reactions are consumed to reduce $\text{CO}_2$ into carbohydrates.

Photosynthetic Pigments and Photosystems

• Pigments: Molecules that absorb specific wavelengths of light. Wavelengths that are not absorbed are reflected or transmitted.

  • Chlorophyll $a$ and Chlorophyll $b$: Primary pigments absorbing violet, blue, and red light while reflecting green light (giving plants their green color).

  • Carotenoids: Accessory pigments absorbing violet, blue, and green light while reflecting yellow and orange. Visible in autumn when chlorophyll decomposes.

• Absorption Spectrum: The precise pattern of light wavelengths absorbed by a pigment.

• Photosystems: Functional light-capturing units embedded within thylakoid membranes composed of three main parts:

  1. Pigment Complex: Array of chlorophyll $a$, chlorophyll $b$, and carotenoid molecules functioning as an antenna to collect solar energy.

  2. Reaction Center: A specialized pair of chlorophyll $a$ molecules that collect concentrated energy and release high-energy electrons.

  3. Electron Acceptor Molecules: Neighboring molecules that receive high-energy electrons escaping from the reaction center.

The Light Reactions: Noncyclic and Cyclic Pathways

• Noncyclic Electron Pathway: Linear electron flow from water through Photosystem II (PS II) and Photosystem I (PS I) to $\text{NADP}^+$:

  • PS II Step: PS II absorbs solar energy. Energized electrons escape the reaction center and enter an Electron Transport Chain (ETC). To replace lost electrons, water is enzymatically split (photolysis):     $\text{H}_2\text{O} \rightarrow 2\,\text{H}^+ + 2\,e^- + \frac{1}{2}\,\text{O}_2$

  • Oxygen ($\text{O}_2$) is released into the atmosphere; $\text{H}^+$ remains in the thylakoid space.

  • ETC Step: High-energy electrons pass through electron carriers (plastoquinone [Pq] and cytochrome complexes). Released energy is used by Pq to pump $\text{H}^+$ from the stroma into the thylakoid space, building a proton gradient.

  • PS I Step: PS I absorbs solar energy, energizing its reaction center. Electrons escape and pass to $\text{NADP}^+$ reductase. Low-energy electrons coming from the ETC replace the electrons lost by PS I.

  • $\text{NADP}^+$ Reduction: The enzyme $\text{NADP}^+$ reductase transfers electrons to $\text{NADP}^+$:     $\text{NADP}^+ + 2\,e^- + \text{H}^+ \rightarrow \text{NADPH}$

• Cyclic Electron Pathway: Alternative pathway used when cell ATP requirements exceed NADPH supply:

  • Electrons leaving PS I are rerouted back to an earlier carrier in the ETC instead of going to $\text{NADP}^+$.

  • As electrons cycle through the ETC back to PS I, they pump additional $\text{H}^+$ into the thylakoid space, driving extra ATP production.

  • The cyclic pathway generates ATP only; it produces no NADPH and releases no $\text{O}_2$.

Thylakoid Structure and Chemiosmosis in Chloroplasts

• Proton Gradient Generation: High $\text{H}^+$ concentration is established inside the thylakoid space relative to the stroma through two mechanisms:

  1. Splitting of $\text{H}_2\text{O}$ inside the thylakoid space produces $\text{H}^+$.

  2. Plastoquinone (Pq) pumps $\text{H}^+$ from the stroma across the thylakoid membrane into the thylakoid space.

• Chemiosmosis:

  • The thylakoid membrane is impermeable to $\text{H}^+$, creating a strong electrochemical gradient.

  • $\text{H}^+$ ions flow down their concentration gradient from the thylakoid space back into the stroma through the internal channel of the ATP Synthase complex.

  • The kinetic energy of flowing protons drives ATP Synthase to phosphorylate ADP:     $\text{ADP} + \text{P}_i \rightarrow \text{ATP}$

The Calvin Cycle: Carbon Fixation, Reduction, and Regeneration

• Overview: Metabolic pathway occurring in the stroma that utilizes ATP and NADPH from light reactions to fix and reduce carbon dioxide into carbohydrates.

• Three Sequential Stages:

  1. Carbon Dioxide Fixation:

  • Atmospheric $\text{CO}_2$ combines with a $5$-carbon molecule called Ribulose-1,5-bisphosphate (RuBP).

  • Yields an unstable $6$-carbon intermediate that immediately splits into two $3$-carbon molecules of $3$-Phosphoglycerate (3PG).

  • Catalyzed by the enzyme RuBP Carboxylase (Rubisco).

  • Rubisco constitutes $20\%$ to $50\%$ of total chloroplast protein because it is exceptionally slow (processing only a few substrate molecules per second).

  1. Carbon Dioxide Reduction:

  • Each $3\text{PG}$ molecule is phosphorylated by ATP and subsequently reduced by NADPH to form Glyceraldehyde-3-phosphate (G3P).

  • Converts lower-energy $3\text{PG}$ into higher-energy G3P storing chemical potential energy.

  1. Regeneration of RuBP:

  • For every $3$ turns of the Calvin cycle, $3$ molecules of $\text{CO}_2$ are fixed, producing $6$ molecules of G3P.

  • $1$ net G3P molecule exits the cycle to be used for carbohydrate synthesis.

  • The remaining $5$ molecules of G3P ($5 \times 3\text{C} = 15\text{C}$) are reshuffled using $3$ ATP molecules to regenerate $3$ molecules of RuBP ($3 \times 5\text{C} = 15\text{C}$), allowing the cycle to continue.

• Fate of G3P (Exported Product): G3P is the primary output of the Calvin cycle and serves as the hydrocarbon skeleton for plant biomolecules:

  • Glucose Phosphate: Combined with fructose to form sucrose for transport; linked to build starch (energy storage) and cellulose (structural cell walls).

  • Fatty Acids & Glycerol: Combined to produce plant oils.

  • Amino Acids: Formed by adding nitrogen groups to G3P derivatives, powering protein synthesis.

Cellular Respiration: Overview and Equations

• Cellular Respiration: The catabolic process by which cells acquire metabolic energy by breaking down organic nutrient molecules (glucose) into $\text{CO}_2$ and $\text{H}_2\text{O}$, building ATP.

• Balanced Chemical Equation:   $\text{C}_6\text{H}_{12}\text{O}_6 + 6\,\text{O}_2 \rightarrow 6\,\text{CO}_2 + 6\,\text{H}_2\text{O} + \text{energy (ATP + heat)}$

• Complete oxidation of $1\,\text{mole}$ of glucose yields $686\,\text{kcal}$ of free energy.

• Glucose breakdown is carried out gradually in sequential steps so that energy is trapped in ATP molecules rather than lost as explosive heat.

• Redox Relationships: Glucose is oxidized (loses hydrogen atoms/$e^-$) to become $\text{CO}_2$; oxygen is reduced (gains hydrogen atoms/$e^-$) to become $\text{H}_2\text{O}$.

Coenzymes of Cellular Respiration

• Respiration pathways rely on specific coenzyme electron carriers to capture high-energy electrons during oxidation steps:

• $\text{NAD}^+$ (Nicotinamide Adenine Dinucleotide): Accepts two electrons and one proton ($\text{H}^+$) to become reduced to NADPH:   $\text{NAD}^+ + 2\,e^- + \text{H}^+ \rightarrow \text{NADH}$

• $\text{FAD}$ (Flavin Adenine Dinucleotide): Serves as an alternative coenzyme. Accepts two electrons and two protons ($\text{H}^+$) to become reduced to $\text{FADH}_2$:   $\text{FAD} + 2\,e^- + 2\,\text{H}^+ \rightarrow \text{FADH}_2$

• Recycling of $\text{NAD}^+$ and $\text{FAD}$ allows cells to maintain efficient metabolism without constantly synthesizing new coenzymes.

Glycolysis: Cytoplasmic Anaerobic Phase

• Glycolysis: A sequence of $10$ enzymatic reactions taking place in the cytoplasm outside the mitochondria. It is anaerobic (requires no oxygen).

• Breaks down one $6$--carbon glucose molecule into two $3$--carbon pyruvate molecules.

• Phase 1: Energy-Investment Steps:

  • Two ATP molecules are hydrolyzed to add phosphate groups to activate glucose.

  • Activated glucose splits into two $3$--carbon molecules of Glyceraldehyde-3-phosphate (G3P).

• Phase 2: Energy-Harvesting Steps:

  • Both G3P molecules undergo oxidation via the removal of hydrogen atoms ($e^- + \text{H}^+$), which are captured by $\text{NAD}^+$ to produce $2\,\text{NADH}$.

  • Four ATP molecules are synthesized via Substrate-Level ATP Synthesis (Substrate-Level Phosphorylation), in which an enzyme directly transfers a high-energy phosphate group from a substrate intermediate to ADP.

  • Both G3P intermediates are converted into pyruvate molecules.

• Summary of Glycolysis Inputs and Outputs:

  • Inputs: $1$ Glucose ($6\text{C}$), $2\,\text{NAD}^+$, $2$ ATP, $4$ ADP + $2\,\text{P}_i$

  • Outputs: $2$ Pyruvate ($3\text{C}$), $2\,\text{NADH}$, $2$ ADP, $4$ ATP ($2$ ATP net gain).

The Preparatory Reaction

• Location: Matrix of the mitochondrion.

• Aerobic Requirement: Pyruvate enters the matrix only if oxygen is available.

• Reaction Mechanism:

  • Pyruvate ($3\text{C}$) is oxidized into a $2$--carbon acetyl group, and one carbon is released as carbon dioxide ($\text{CO}_2$).

  • High-energy electrons are removed by $\text{NAD}^+$, forming $\text{NADH}$.

  • The $2$--carbon acetyl group combines with Coenzyme A (CoA) to form Acetyl-CoA.

• Stoichiometry: Because glycolysis produces two pyruvates per glucose, the prep reaction occurs twice per glucose molecule:

  • Outputs per Glucose: $2$ Acetyl-CoA, $2\,\text{NADH}$, $2\,\text{CO}_2$

  • Acetyl-CoA transports acetyl groups into the Citric Acid Cycle; $\text{CO}_2$ diffuses out of the cell into blood to be exhaled by lungs; $\text{NADH}$ delivers electrons to the ETC.

The Citric Acid Cycle (Krebs Cycle)

• Location: Mitochondrial matrix.

• Reaction Mechanism:

  • The $2$--carbon acetyl group of Acetyl-CoA combines with a $4$--carbon oxaloacetate molecule, forming a $6$--carbon citrate molecule.

  • Citrate undergoes oxidation through a cyclic series of reactions:

  • Oxidation steps reduce $\text{NAD}^+$ to $\text{NADH}$ ($3$ times per turn) and $\text{FAD}$ to $\text{FADH}_2$ ($1$ time per turn).

  • Two carbon atoms are released as $\text{CO}_2$ per turn.

  • One ATP is produced per turn via substrate-level ATP synthesis.

• Turns per Glucose: Turns twice for every original glucose molecule (once for each Acetyl-CoA).

• Citric Acid Cycle Inputs and Outputs (Per Glucose / 2 Turns):

  • Inputs: $2$ Acetyl groups ($2\text{C}$), $6\,\text{NAD}^+$, $2\,\text{FAD}$, $2$ ADP + $2\,\text{P}_i$

  • Outputs: $4\,\text{CO}_2$, $6\,\text{NADH}$, $2\,\text{FADH}_2$, $2$ ATP.

• All $6$ carbon atoms original to glucose are fully released as $\text{CO}_2$ by the end of the Citric Acid Cycle ($2$ from prep step, $4$ from citric acid cycle).

The Electron Transport Chain and Oxidative Phosphorylation

• Location: Cristae (inner mitochondrial membrane) in eukaryotes; plasma membrane in prokaryotes.

• Components: A series of membrane-bound electron carriers consisting of $3$ protein complexes:

  1. NADH-Q reductase complex

  2. Cytochrome reductase complex

  3. Cytochrome oxidase complex

  • Accompanied by $2$ mobile electron carriers: Coenzyme Q and Cytochrome c.

  • Cytochromes: Class of proteins containing a tightly bound heme group with a central iron atom ($\text{Fe}$). The iron accepts an electron to become reduced ($\text{Fe}^{2+}$) and gives up an electron to become oxidized ($\text{Fe}^{3+}$).

• Electron Trapping and Flow Sequence:   $\text{Glucose} \rightarrow \text{NADH / FADH}_2 \rightarrow \text{Electron Transport Chain} \rightarrow \text{Oxygen}$

  • $\text{NADH}$ and $\text{FADH}_2$ deliver high-energy electrons to the chain.

  • High-energy electrons enter; low-energy electrons leave.

• Proton Gradient and Chemiosmosis:

  • Energy released during sequential redox reactions down the ETC is used to pump $\text{H}^+$ from the matrix across the inner membrane into the intermembrane space.

  • This creates a steep electrochemical $\text{H}^+$ gradient across the cristae.

  • $\text{H}^+$ flows down its gradient back into the matrix through ATP Synthase, driving oxidative phosphorylation of ADP to ATP.

• Oxygen as the Final Electron Acceptor: Oxygen ($\text{O}_2$) sits at the terminus of the ETC. It accepts low-energy electrons, combines with matrix $\text{H}^+$ ions, and forms water ($\text{H}_2\text{O}$):   $\frac{1}{2}\,\text{O}_2 + 2\,e^- + 2\,\text{H}^+ \rightarrow \text{H}_2\text{O}$

  • Oxygen is required to pull electrons off the end of the chain. Without $\text{O}_2$, the ETC backs up, stopping ATP synthesis.

ATP Yield and Metabolic Efficiency

• Substrate-Level ATP Yield:

  • Glycolysis: $2$ ATP net.

  • Citric Acid Cycle: $2$ ATP.

  • Subtotal: $4$ ATP.

• Oxidative Phosphorylation Yield (via ETC & Chemiosmosis):

  • Each $\text{NADH}$ produced inside the mitochondrion yields approximately $3$ ATP.

  • Each $\text{FADH}_2$ yields approximately $2$ ATP (enters ETC later at Coenzyme Q, bypassing complex 1).

  • $2\,\text{NADH}$ from Glycolysis $\rightarrow 4$ or $6$ ATP (depending on the tissue shuttle mechanism transferring cytoplasmic $e^-$ across mitochondrial membranes).

  • $2\,\text{NADH}$ from Pyruvate Prep Step $\rightarrow 6$ ATP.

  • $6\,\text{NADH}$ from Citric Acid Cycle $\rightarrow 18$ ATP.

  • $2\,\text{FADH}_2$ from Citric Acid Cycle $\rightarrow 4$ ATP.

  • Total ETC Yield: $32$ to $34$ ATP.

• Total Theoretical ATP Yield: $36$ to $38$ ATP per glucose molecule.

• Actual Cellular ATP Yield: Approximately $30$ ATP per glucose molecule.

• Factors Reducing Yield:

  • Energy cost of shuttle mechanisms transporting cytosolic $\text{NADH}$ electrons into matrix.

  • ATP required to actively transport ADP and pyruvate into the mitochondrial matrix.

  • Proton gradient leakage and secondary transport uses of $\text{H}^+$.

• Energy Efficiency: Transfer of glucose bond energy to ATP captures approximately $32\%$ to $39\%$ of total free energy; remaining energy is dissipated as body heat.

Anaerobic Respiration: Fermentation Pathways

• Fermentation: An anaerobic pathway occurring in the cytoplasm when oxygen is deficient.

• Primary Biological Function: To regenerate $\text{NAD}^+$ from $\text{NADH}$. Glycolysis requires $\text{NAD}^+$ as an electron acceptor; if $\text{NADH}$ cannot unload electrons at an active ETC, $\text{NAD}^+$ depletes, halting glycolysis and all ATP synthesis.

• Mechanism: Pyruvate produced in glycolysis is reduced by $\text{NADH}$ into fermentation products, freeing $\text{NAD}^+$ to return to glycolysis.

• Two Primary Fermentation Pathways:

  1. Lactic Acid Fermentation: Carried out by certain bacteria, fungi, and animal skeletal muscle cells. Pyruvate is reduced directly to lactate (lactic acid). Used commercially to produce cheese, yogurt, and sauerkraut.

  2. Alcoholic Fermentation: Carried out by yeasts and microorganisms. Pyruvate is reduced to ethyl alcohol and carbon dioxide ($\text{CO}_2$). Used commercially to produce alcoholic beverages and bread dough expansion.

• Fermentation Energy Yield and Efficiency:

  • Yields only the $2$ net ATP produced during glycolysis.

  • Provides $14.6\,\text{kcal/mol}$ of glucose energy.

  • Efficiency calculation: $\frac{14.6}{686} \times 100 = 2.1\%$ efficiency.

• Advantages and Disadvantages:

  • Advantages: Provides an immediate, rapid burst of ATP energy in the absence of oxygen; keeps glycolysis operational.

  • Disadvantages: Extreme inefficiency compared to aerobic respiration ($2$ ATP vs $30\text{--}38$ ATP). Lactate and alcohol are toxic to cells. Lactate accumulation changes cellular pH, causing muscle fatigue and oxygen debt.

Metabolic Pool: Catabolism and Anabolism of Fats and Proteins

• Metabolic Pool Concept: The collective sum of cellular substrates used interchangeably to synthesize or degrade biomolecules.

• Catabolism (Breakdown Reactions):

  • Fat Catabolism: Lipids break down into glycerol and three fatty acid chains. Glycerol converts to G3P to enter glycolysis. Long fatty acid chains undergo beta-oxidation, splitting into $2$--carbon acetyl groups that enter the Citric Acid Cycle as Acetyl-CoA. Complete respiration of an $18$--carbon fatty acid yields $9$ Acetyl-CoA molecules, producing approximately $108$ ATP (fats are highly efficient, concentrated energy stores).

  • Protein Catabolism: Proteins break down into amino acids. Amino acids undergo deamination (removal of the amino group, $-\text{NH}_2$) in the liver. Removed amino groups convert to toxic ammonia ($\text{NH}_3$), which enters the urea cycle to form urea, excreted by kidneys. The remaining carbon skeletons enter glycolysis, the prep reaction, or the Citric Acid Cycle at different intermediate points depending on carbon length.

• Anabolism (Synthetic Building Reactions):

  • Energy released during catabolism powers anabolic pathways.

  • Fat Synthesis: Excess carbohydrate consumption supplies excess G3P (converted to glycerol) and excess acetyl groups (joined to form fatty acid chains), building fats.

  • Amino Acid Synthesis: Organisms synthesize amino acids via transamination (transferring an amino group to an organic acid intermediate of the Citric Acid Cycle).

  • Essential vs Nonessential Amino Acids: Plants synthesize all $20$ required amino acids. Animals lack essential enzymes and can synthesize only $11$ nonessential amino acids; humans must acquire the remaining $9$ essential amino acids through diet.

Comparative Analysis: Photosynthesis vs. Cellular Respiration

• Photosynthesis and Cellular Respiration form a balanced, complementary ecological and cellular cycle:

• Metabolic and Chemical Comparisons:

  • Photosynthesis Equation: $6\,\text{CO}_2 + 6\,\text{H}_2\text{O} + \text{solar energy} \rightarrow \text{C}_6\text{H}_{12}\text{O}_6 + 6\,\text{O}_2$

  • Anabolic, endergonic ($+\Delta G$), reduces $\text{CO}_2$ to glucose, oxidizes $\text{H}_2\text{O}$ to $\text{O}_2$

  • Cellular Respiration Equation: $\text{C}_6\text{H}_{12}\text{O}_6 + 6\,\text{O}_2 \rightarrow 6\,\text{CO}_2 + 6\,\text{H}_2\text{O} + \text{energy (ATP + heat)}$

  • Catabolic, exergonic ($-\Delta G$), oxidizes glucose to $\text{CO}_2$, reduces $\text{O}_2$ to $\text{H}_2\text{O}$.

• Organelle Comparisons:

  • Chloroplasts: Inner membrane forms thylakoid stacks (grana); fluid stroma contains Calvin cycle enzymes. Photosynthetic ETC on thylakoid membrane pumps $\text{H}^+$ into thylakoid space; solar energy powers $e^-$.

  • Mitochondria: Inner membrane forms cristae folds; fluid matrix contains Prep step and Citric Acid Cycle enzymes. Respiratory ETC on cristae membrane pumps $\text{H}^+$ into intermembrane space; glucose nutrient breakdown powers $e^-$.

  • Both organelles utilize electron transport chains and chemiosmosis across internal membranes to establish proton gradients that power ATP Synthase.

• Flow of Energy vs Cycling of Chemicals:

  • Chemicals Cycle: Carbon dioxide and oxygen cycle continuously between organelles and organisms. $\text{CO}_2$ released by mitochondrial respiration is absorbed by chloroplasts for carbohydrate synthesis; $\text{O}_2$ released by chloroplasts is utilized by mitochondria as final electron acceptor.

  • Energy Flows: Energy does not cycle. Solar energy enters chloroplasts, converts to chemical energy in carbohydrates, passes to mitochondria, converts to ATP, and is ultimately dissipated into the environment as unusable body heat. All life depends on a continuous, uninterrupted solar energy supply.