Molecular Biology of the Cell · Part 1 of 2 · 10 MCQs per part
Part 1 of 2
Chemical Bonds, Water, and Macromolecules
Life is chemistry — every heartbeat, every thought, every cell division is underpinned by atoms forming and breaking bonds. Understanding which bonds exist in biology, and why water is the universal solvent, unlocks the logic of all cellular chemistry.
2.1 Chemical Bonds in Biology
Atoms interact through chemical bonds. The two major categories relevant to biology are covalent bonds and noncovalent bonds. Covalent bonds involve the sharing of electron pairs between atoms and are strong (bond energies of 150–900 kJ/mol). They form the backbone of biological macromolecules. Noncovalent bonds are individually weak (1–30 kJ/mol) but collectively powerful when present in large numbers.
Key term
Covalent bond
A chemical bond formed by the sharing of one or more electron pairs between two atoms; the basis of stable molecules in biochemistry.
Noncovalent interactions include: hydrogen bonds (between a hydrogen atom bonded to an electronegative atom and another electronegative atom); electrostatic interactions (ionic bonds between opposite charges); van der Waals forces (transient dipole-induced dipole attractions); and the hydrophobic effect (the tendency of nonpolar groups to cluster together in aqueous solution, driven by the increase in entropy of surrounding water molecules).
2.2 Water and Its Properties
Water is the medium in which all cellular chemistry occurs. Its unique properties arise from its polarity and ability to form hydrogen bonds. Each water molecule can donate two and accept two hydrogen bonds, creating a dynamic hydrogen-bond network. Key properties include: high specific heat (resists temperature change), high heat of vaporization (effective coolant through evaporation), and the capacity to dissolve polar and ionic solutes (making it an excellent solvent).
Key term
Hydrogen bond
A noncovalent interaction between a hydrogen atom covalently bonded to an electronegative atom (N, O, F) and a lone pair of electrons on another electronegative atom.
The pH of a solution reflects the concentration of hydrogen ions [H⁺]. Pure water has a pH of 7 (neutral). Acids donate protons; bases accept them. Biological systems maintain pH within narrow ranges using buffers — weak acid/conjugate base pairs that resist pH changes.
2.3 Biological Macromolecules
Cells build large polymers (macromolecules) from small monomer units by condensation reactions (releasing water) and break them down by hydrolysis (adding water). The four major classes of macromolecules are: proteins (amino acid polymers), nucleic acids (nucleotide polymers), polysaccharides (sugar polymers), and lipids (not true polymers, but assembled from fatty acids and glycerol).
Carbohydrates serve as energy stores (glycogen, starch) and structural materials (cellulose, chitin). They are also important in cell signaling and cell-cell recognition via glycoproteins and glycolipids on the cell surface. Lipids include fats (energy storage), phospholipids (membrane bilayers), and sterols (e.g., cholesterol, which modulates membrane fluidity).
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Pause & Recall
Why is the hydrophobic effect considered an entropic phenomenon rather than a true attractive force?
Nonpolar molecules in water force surrounding water molecules into a restricted, ordered arrangement, reducing entropy. When nonpolar groups cluster together, they release water molecules to form more random arrangements, increasing system entropy. The driving force is therefore the entropy gain of water, not an attraction between the nonpolar groups themselves.
Practice Questions — Part 1Score: 0 / 10
1. Which type of chemical bond is strongest?
Covalent bonds involve shared electron pairs and have bond energies of 150–900 kJ/mol, far exceeding noncovalent interactions. Hydrogen bonds are ~10–30 kJ/mol and van der Waals forces are even weaker.
2. The hydrophobic effect is primarily driven by:
The hydrophobic effect is entropic: nonpolar molecules force surrounding water into ordered cages. When they cluster, water is released to higher-entropy disordered states, driving the system thermodynamically.
3. A solution with a pH of 5 compared to one with a pH of 7 has:
pH is a logarithmic scale: each unit represents a 10-fold change in [H⁺]. pH 5 vs pH 7 is a 2-unit difference = 10² = 100-fold more H⁺ at pH 5.
4. Which of the following correctly pairs a macromolecule class with its monomer?
Polysaccharides are polymers of monosaccharides (simple sugars). Proteins are polymers of amino acids; DNA is a polymer of nucleotides; lipids are not true polymers.
5. Water's high specific heat is biologically important because it:
High specific heat means water absorbs or releases large amounts of heat per degree of temperature change. This buffers cells and organisms against rapid temperature fluctuations that would otherwise denature proteins and disrupt cellular chemistry.
6. Which lipid is a major component of all biological membranes?
Phospholipids are amphipathic molecules with a hydrophilic phosphate head and two hydrophobic fatty acid tails. Their spontaneous arrangement into bilayers forms the structural basis of all biological membranes.
7. A buffer resists pH changes by:
A buffer consists of a weak acid and its conjugate base. When H⁺ is added, the base absorbs it; when H⁺ is removed, the acid releases it. This keeps pH relatively stable around the pKa of the buffering pair.
8. Cellulose and glycogen are both polymers of glucose. Why do they have such different properties?
Cellulose uses β-1,4 linkages, producing linear chains that stack into rigid fibers (structural). Glycogen uses α-1,4 linkages with α-1,6 branch points, creating a highly branched, readily hydrolyzable energy store. The bond geometry determines function.
9. Van der Waals forces arise from:
Van der Waals forces result from random fluctuations in electron distribution creating momentary dipoles that induce dipoles in adjacent atoms, producing a weak attractive force. They become significant when many atoms are in very close contact, as in tightly packed protein cores.
10. Macromolecers are synthesized from monomers by:
Condensation (dehydration synthesis) reactions join monomers by forming a covalent bond while releasing a water molecule. The reverse process, hydrolysis, breaks these bonds by adding water.
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Section B · Recall Questions · Part 1
Type your answer, then click Check to reveal the sample answer.
B1
Distinguish between covalent and noncovalent bonds in terms of their strength and biological roles.
Sample answer: Covalent bonds share electron pairs and are strong (150–900 kJ/mol), forming the backbone of molecules. Noncovalent bonds (hydrogen bonds, ionic, van der Waals, hydrophobic) are individually weak (1–30 kJ/mol) but numerous; they mediate protein folding, DNA base pairing, and molecular recognition.
B2
Explain why water molecules form hydrogen bonds with each other.
Sample answer: Water is polar: oxygen is highly electronegative, pulling electron density away from the two hydrogen atoms. The partially positive H atoms are attracted to the lone pairs on the electronegative oxygen of adjacent water molecules, forming hydrogen bonds.
B3
Define pH and explain what it means for a solution to be acidic vs. basic.
Sample answer: pH = -log[H⁺]. Solutions with pH below 7 are acidic ([H⁺] > [OH⁻]); above 7 are basic ([OH⁻] > [H⁺]); pH 7 is neutral. Acids donate protons; bases accept protons.
B4
Why do nonpolar molecules tend to cluster together in water?
Sample answer: Nonpolar molecules cannot form hydrogen bonds with water, so surrounding water molecules are forced into ordered cage-like arrangements, reducing entropy. When nonpolar molecules cluster, they free surrounding water molecules into disordered arrangements, increasing system entropy — this is the hydrophobic effect.
B5
Describe the structure of a phospholipid and explain how this structure leads to bilayer formation.
Sample answer: A phospholipid has a hydrophilic phosphate-containing head and two hydrophobic fatty acid tails — it is amphipathic. In water, the hydrophobic effect drives phospholipids to arrange in bilayers, with tails facing inward and heads facing the aqueous environment.
B6
Compare condensation and hydrolysis reactions in the context of macromolecule synthesis and breakdown.
Sample answer: Condensation (dehydration synthesis) joins monomers by forming a covalent bond and releasing water — used in building proteins, polysaccharides, and nucleic acids. Hydrolysis reverses this by adding water to break the bond, releasing monomers during digestion or intracellular recycling.
B7
Name two biological roles of carbohydrates and give a specific example of each.
Sample answer: (1) Energy storage: glycogen (animals) and starch (plants) are branched glucose polymers rapidly mobilized for ATP synthesis. (2) Structural support: cellulose forms the cell walls of plants; chitin strengthens fungal cell walls and insect exoskeletons.
B8
Describe van der Waals forces and state under what conditions they become significant in proteins.
Sample answer: Van der Waals forces are very weak attractions (~ 0.1–4 kJ/mol) arising from transient, fluctuating electron distributions. They become significant when many atoms are in very close and precise contact, as in tightly packed hydrophobic protein cores where their cumulative contribution is substantial.
B9
What role does cholesterol play in animal cell membranes?
Sample answer: Cholesterol is a sterol that inserts between phospholipid tails in the bilayer. It moderates membrane fluidity: at high temperatures it reduces fluidity (by restraining phospholipid movement); at low temperatures it prevents the membrane from freezing (by disrupting tight packing of tails).
B10
Explain why ionic and polar molecules dissolve readily in water, whereas nonpolar molecules do not.
Sample answer: Water molecules are polar and form hydrogen bonds. Ionic solutes are surrounded by water molecules that orient their partial charges toward the ions (hydration shells), dispersing them. Polar solutes form hydrogen bonds with water. Nonpolar molecules cannot interact favorably with water and are excluded by the hydrophobic effect.
Section C · Critical Thinking · Part 1
Develop analytical responses, then compare with the sample.
C1
Individual noncovalent bonds are very weak, yet they are essential for protein folding and DNA base pairing. Explain how this apparent paradox is resolved.
Sample answer: The paradox resolves because thousands of noncovalent bonds act simultaneously. A protein may form hundreds of hydrogen bonds, van der Waals contacts, and hydrophobic interactions — their cumulative stabilization energy is large. Moreover, the specificity of their combined geometry ensures only the correct folded structure or correct base pair is stable. Individual weakness is advantageous: it allows rapid, reversible rearrangements needed for dynamic biological processes.
C2
Why must cells maintain a narrow pH range, and what happens to proteins when pH deviates significantly from physiological values?
Sample answer: Proteins are folded by noncovalent interactions that depend on the ionization states of amino acid side chains. Extreme pH alters these charges, disrupting the electrostatic and hydrogen-bond networks that maintain structure. This causes denaturation — loss of 3D structure and function. Enzymes, which require precise active-site geometry, are particularly sensitive. Buffers (e.g., bicarbonate/CO₂ in blood) maintain physiological pH near 7.4.
C3
Explain why phospholipid bilayers self-assemble spontaneously and why this is thermodynamically favorable.
Sample answer: Phospholipids are amphipathic. In water, exposing hydrophobic tails to water is thermodynamically unfavorable (increases ordered water). A bilayer arrangement buries the tails away from water, releasing ordered water molecules and increasing entropy. The free energy of bilayer formation (ΔG < 0) reflects this entropy gain. No external energy is required — assembly is spontaneous and driven by the hydrophobic effect.
C4
Both cellulose and glycogen are glucose polymers, yet one is digestible by humans and the other is not. Analyze how the type of glycosidic bond determines this difference in digestibility.
Sample answer: Glycogen uses α-1,4 (and α-1,6 at branches) linkages. Human amylases and glucosidases are shaped to cleave α-glycosidic bonds. Cellulose uses β-1,4 linkages, which create straight chains that pack into rigid fibers. Humans lack the enzyme cellulase to hydrolyze β-1,4 bonds. The stereochemistry of a single type of bond completely changes the polymer's shape, fiber-forming ability, and enzyme accessibility.
C5
Life as we know it depends on water. Describe three properties of water that are essential to cellular life and explain why each matters.
Sample answer: (1) Polarity/solvent ability: dissolves ions and polar molecules needed for metabolism. (2) High specific heat: buffers cells against temperature extremes, protecting enzyme structure. (3) Participation in reactions: water is a substrate in hydrolysis and a product of condensation; it directly participates in metabolic chemistry. (4) Cohesion/adhesion: enables water transport in plants and surface tension effects. Any three with clear reasoning is acceptable.
Section D · Interactive Questions · Part 1
Enter your answer and click Check for instant feedback.
D1
What type of bond joins amino acids together in a protein chain? (two words)
D2
What is the pH of pure water at 25°C? (number)
D3
Which polysaccharide is the primary energy storage molecule in animal cells? (one word)
D4
The tendency of nonpolar molecules to cluster in water is called the _______ effect. (one word)
D5
Is the synthesis of a polymer from monomers a condensation or hydrolysis reaction? (one word)
Part 2 →
With a command of the chemical building blocks, we now turn to thermodynamics and bioenergetics — how cells use free energy, ATP, enzymes, and electron carriers to power all of life's processes.
Part 2 of 2
Energy, Enzymes, and Metabolic Pathways
2.4 Free Energy and Chemical Equilibrium
The Gibbs free energy (G) of a system determines whether a reaction is thermodynamically spontaneous. A reaction proceeds spontaneously when ΔG < 0 (exergonic). When ΔG > 0, the reaction is endergonic and requires an energy input. At equilibrium, ΔG = 0 and the forward and reverse reaction rates are equal.
Key term
Free energy (ΔG)
The energy available to do work in a system at constant temperature and pressure; ΔG < 0 for spontaneous reactions, ΔG > 0 for non-spontaneous reactions.
Cells are not at equilibrium — they are open systems that continuously exchange matter and energy with their environment. By coupling exergonic reactions (like ATP hydrolysis, ΔG = −30 kJ/mol under cellular conditions) to endergonic ones, cells drive thermodynamically unfavorable reactions forward.
2.5 ATP: The Energy Currency of the Cell
ATP (adenosine triphosphate) is the primary carrier of chemical energy in cells. Hydrolysis of the terminal phosphoanhydride bond releases energy used to drive biosynthesis, membrane transport, and mechanical work. The high energy yield of ATP hydrolysis results from electrostatic repulsion between the phosphate groups and resonance stabilization of the products (ADP + Pi).
ATP is regenerated from ADP and inorganic phosphate by cellular respiration (in mitochondria) and photosynthesis (in chloroplasts). The cell recycles its entire ATP pool hundreds of times per day.
2.6 Catalysis and Enzymes
Enzymes are biological catalysts — almost always proteins — that accelerate chemical reactions by lowering the activation energy (Ea). They do not alter the thermodynamics (the ΔG of a reaction), only its kinetics. An enzyme's catalytic power resides in its active site, a precisely shaped pocket that binds the substrate through noncovalent interactions and positions it for bond making or breaking.
Key term
Activation energy
The energy required to initiate a chemical reaction; enzymes lower activation energy, dramatically increasing reaction rates without being consumed.
Enzyme activity can be regulated by inhibitors (competitive, noncompetitive) and by allosteric regulation — binding of a regulatory molecule at a site distinct from the active site that changes enzyme conformation and activity. Many metabolic enzymes are allosterically inhibited by the end product of the pathway they catalyze (feedback inhibition), providing efficient control of metabolic flux.
2.7 Oxidation–Reduction Reactions
Oxidation–reduction (redox) reactions involve the transfer of electrons between molecules. When a molecule loses electrons it is oxidized; when it gains electrons it is reduced. In cellular respiration, glucose is oxidized and oxygen is reduced. Electron carriers like NAD⁺/NADH and FAD/FADH₂ shuttle electrons from metabolic oxidations to the electron transport chain, where their energy is harnessed to synthesize ATP.
Practice Questions — Part 2Score: 0 / 10
1. A reaction with ΔG < 0 is described as:
ΔG < 0 defines an exergonic (energy-releasing) reaction that proceeds spontaneously. ΔG > 0 is endergonic; ΔG = 0 is equilibrium. Note that spontaneous does not mean fast — enzymes are still needed for adequate reaction rates.
2. How do enzymes increase the rate of a reaction?
Enzymes lower activation energy by stabilizing the transition state and positioning substrates optimally for reaction. They do not change ΔG (thermodynamics), only kinetics. They are not consumed and do not supply energy directly.
3. Feedback inhibition of a metabolic pathway occurs when:
Feedback (end-product) inhibition is a classic form of allosteric regulation where the end product of a pathway binds to and inhibits an early enzyme (often the first committed step), preventing overproduction and wasting resources.
4. In cellular respiration, NAD⁺ acts as:
NAD⁺ is an electron carrier. It accepts electrons (and a proton) from metabolic oxidations to become NADH. NADH then donates these electrons to the electron transport chain, driving ATP synthesis. O₂ is the terminal electron acceptor in aerobic respiration.
5. A competitive inhibitor reduces enzyme activity by:
A competitive inhibitor resembles the substrate and binds reversibly to the active site, preventing substrate binding. It competes directly with the substrate; its effect can be overcome by increasing substrate concentration.
6. Which statement about ATP hydrolysis is correct?
ATP hydrolysis (ATP + H₂O → ADP + Pi) is exergonic (ΔG ≈ −30 kJ/mol under typical cellular conditions). This energy is coupled to endergonic reactions in biosynthesis, active transport, and motor protein activity.
7. Oxidation of a molecule means it:
Oxidation = loss of electrons (mnemonic: OIL RIG — Oxidation Is Loss, Reduction Is Gain). In respiration, glucose is oxidized (loses electrons) and oxygen is reduced (gains electrons).
8. Allosteric regulation differs from competitive inhibition in that:
Allosteric regulators bind at a site separate from the active site (the allosteric site), inducing conformational changes that either activate or inhibit the enzyme. Competitive inhibitors, by contrast, bind directly to the active site.
9. Why are living cells described as "open systems" in thermodynamic terms?
Open systems exchange both energy and matter with their surroundings. Cells consume nutrients, expel waste, and maintain a non-equilibrium steady state. This is essential for life — at equilibrium, all reactions stop, which equals death.
10. The electrons carried by NADH are ultimately transferred to which molecule in aerobic respiration?
Oxygen (O₂) is the terminal electron acceptor in aerobic respiration. Electrons from NADH pass through the electron transport chain complexes and are finally accepted by O₂, forming water (H₂O).
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Section B · Recall Questions · Part 2
Type your answer, then click Check to reveal the sample answer.
B1
What is Gibbs free energy and how does its sign (ΔG) predict whether a reaction is spontaneous?
Sample answer: Gibbs free energy (G) is the energy in a system available to do work. ΔG < 0 (exergonic): reaction is spontaneous. ΔG > 0 (endergonic): requires energy input. ΔG = 0: system at equilibrium.
B2
Why does ATP hydrolysis release free energy, and what are the products of this reaction?
Sample answer: ATP hydrolysis (ATP + H₂O → ADP + Pi + ~30 kJ/mol) releases energy because: the phosphate groups in ATP are electrostatically repelled; products (ADP and Pi) are more resonance-stabilized; products are more solvated. Energy is released as heat and available to drive cellular work.
B3
Describe the active site of an enzyme and explain the induced-fit model of substrate binding.
Sample answer: The active site is a precisely shaped pocket on the enzyme that binds the specific substrate through noncovalent interactions (hydrogen bonds, van der Waals, electrostatic). In the induced-fit model, both enzyme and substrate change shape slightly upon binding, producing a tighter, catalytically competent complex — unlike the rigid lock-and-key model.
B4
Define oxidation and reduction, and explain the role of NAD⁺/NADH in cellular metabolism.
Sample answer: Oxidation = loss of electrons; reduction = gain of electrons (OIL RIG). NAD⁺ accepts electrons (+ H⁺) from metabolic substrates, becoming NADH (reduced). NADH delivers electrons to the mitochondrial electron transport chain, where they power ATP synthesis via oxidative phosphorylation.
B5
Explain feedback inhibition in a metabolic pathway and why it is an efficient regulatory mechanism.
Sample answer: Feedback inhibition occurs when the end product of a pathway binds allosterically to an early enzyme (typically the first committed step), inhibiting its activity and slowing further product synthesis. It is efficient because it self-regulates supply — when enough product exists, production stops; when product is used up, inhibition lifts and synthesis resumes.
B6
Why must living cells avoid thermodynamic equilibrium, and how do they achieve this?
Sample answer: At equilibrium, ΔG = 0 — no net reactions occur, meaning no work can be done. A cell at equilibrium is dead. Cells maintain a non-equilibrium steady state by continuously importing nutrients and exporting waste (open system), coupling exergonic and endergonic reactions, and using ATP to shift equilibria of otherwise unfavorable reactions.
B7
What is the transition state of a reaction and how do enzymes stabilize it?
Sample answer: The transition state is the highest-energy, unstable configuration of atoms through which reactants must pass to become products. Enzymes lower the activation energy by providing a surface that stabilizes the transition state (complementary shape and charge), making it more probable for reactants to reach this state.
B8
Explain reaction coupling and give an example from cellular metabolism.
Sample answer: Reaction coupling links an exergonic reaction to an endergonic one so the overall ΔG is negative. Example: amino acid activation uses ATP hydrolysis (ΔG = −30 kJ/mol) to drive the attachment of amino acids to tRNA (ΔG = +30 kJ/mol). The combined ΔG ≈ 0 or negative, making translation thermodynamically possible.
B9
Summarize how the electron transport chain uses electrons from NADH to synthesize ATP.
Sample answer: Electrons from NADH are passed through protein complexes (I, III, IV) in the inner mitochondrial membrane. As electrons flow, protons are pumped from the matrix to the intermembrane space, creating an electrochemical gradient. Protons flow back through ATP synthase (Complex V) down this gradient, driving the rotation of the enzyme to synthesize ATP from ADP + Pi (chemiosmosis).
B10
How does a noncompetitive inhibitor differ from a competitive inhibitor in its mechanism of action?
Sample answer: A noncompetitive inhibitor binds to a site other than the active site (allosteric site), changing the enzyme's conformation so that even bound substrate is not converted to product efficiently. Unlike competitive inhibition, increasing substrate concentration cannot overcome noncompetitive inhibition because the inhibitor does not compete with the substrate.
Section C · Critical Thinking · Part 2
Develop analytical responses, then compare with the sample.
C1
A student says, "If ΔG < 0, the reaction will happen quickly." Identify the flaw in this reasoning and explain the relationship between thermodynamics and kinetics.
Sample answer: Thermodynamics (ΔG) tells us the direction and energy change of a reaction at equilibrium — whether it is favorable — but says nothing about its rate. Kinetics is governed by activation energy. Diamond converting to graphite has ΔG < 0 yet is immeasurably slow at room temperature. Cells use enzymes to lower activation energy and control which thermodynamically favorable reactions occur at biologically useful rates.
C2
Some poisons, like cyanide, work by irreversibly inhibiting cytochrome c oxidase (Complex IV). Explain why blocking this single enzyme is rapidly lethal.
Sample answer: Complex IV transfers electrons to O₂, the final step of the electron transport chain. Blocking it halts the entire chain: no proton gradient forms, ATP synthase stops, and ATP production collapses. Cells (especially neurons and heart muscle) with high ATP demand cannot survive minutes without oxidative phosphorylation. Irreversible inhibition means the enzyme is permanently inactivated; only synthesis of new protein can restore function.
C3
Estimate why a cell needs to recycle its ATP pool hundreds of times per day rather than simply having a large stockpile of ATP molecules.
Sample answer: A resting human uses ~40 kg of ATP per day but the body contains only ~250 g of ATP at any moment — continuous regeneration is essential. Storing all needed ATP at once would require enormous molecular mass, saturating the cell. Regeneration via respiration links ATP supply directly to metabolic demand, providing fine control over energy production. The ADP/ATP ratio itself signals energy status and regulates metabolic pathways.
C4
Explain why electrons flow spontaneously from NADH through the electron transport chain to oxygen. What thermodynamic principle drives this?
Sample answer: Electrons flow spontaneously from molecules of lower reduction potential (higher electron-donating tendency) to those of higher reduction potential (stronger electron acceptors). NADH has a reduction potential of about −0.32 V; O₂ has +0.82 V. The large difference (1.14 V) corresponds to a large negative ΔG (−220 kJ per 2 electrons), driving spontaneous electron flow and proton pumping.
C5
Many drugs work as enzyme inhibitors. Discuss what properties make an ideal drug-target enzyme and how structural knowledge of the enzyme aids drug design.
Sample answer: An ideal drug-target enzyme is essential for the pathogen or cancer cell but differs sufficiently from host enzymes to allow selective inhibition. Knowing the 3D structure of the active site allows rational design of molecules that fit with high affinity and specificity. For example, HIV protease inhibitors were designed using crystallographic structures of the viral enzyme. Structural differences between bacterial and eukaryotic ribosomes underlie the selectivity of many antibiotics.
Section D · Interactive Questions · Part 2
Enter your answer and click Check for instant feedback.
D1
A reaction with ΔG < 0 is said to be _______ (one word).
D2
What molecule accepts electrons from NADH at the end of the electron transport chain? (one word)
D3
The loss of electrons from a molecule is called _______ (one word).
D4
What type of inhibitor resembles the substrate and blocks the enzyme's active site? (one word)
D5
What full name is given to the process by which proton flow through ATP synthase drives ATP synthesis? (two words)