Cell Chemistry and Bioenergetics Notes

Chemical Systems and Living Creatures

• Living creatures were once believed to possess a "Vital Force" or "animus." We now understand that they adhere to chemical and physical laws.
• The chemistry of life is unique:
  • It's primarily based on carbon compounds, known as organic chemistry.
  • Cells are 70% water, making chemical reactions largely aqueous.
  • Cell chemistry is incredibly complex, far more so than any other known chemical system.
  • Cells contain small carbon molecules, but most carbon atoms are in large polymeric molecules (macromolecules).
• These macromolecules dictate life's characteristics, such as growth and reproduction.

Chemical Components of a Cell

• Living organisms consist of a small subset of the 92 naturally occurring elements.
• Carbon (C), hydrogen (H), nitrogen (N), and oxygen (O) constitute 96.5% of an organism's weight.
• Atoms are linked by covalent bonds to form molecules.
• Covalent bonds are strong, resisting thermal energies within a cell.
• Noncovalent bonds can hold two different molecules together, but are weaker (Figure 2-2).
• Noncovalent bonds are critical for temporary molecular associations needed for biological functions.

Water and Hydrogen Bonds

• Cell reactions occur in an aqueous environment.
• Water molecules (H2O) have polar covalent bonds (O is more attractive to electrons than H).
• This unequal distribution of electrons leads to hydrogen bonds, where a positive region of one water molecule is attracted to a negative region of another.
• Hydrogen bonds are weak and easily broken by thermal motions.
• Water's liquid state at room temperature, high boiling point, and surface tension are due to hydrogen bonds.
• Polar molecules (like alcohols) and charged molecules (ions) are hydrophilic and dissolve in water.
• Hydrophobic molecules are uncharged and don't form hydrogen bonds, thus not dissolving in water. Hydrocarbons are examples.
• Cell membranes utilize hydrophobic properties with hydrocarbon tails.

Noncovalent Attractions

• Biology depends on molecule-specific binding aided by noncovalent bonds:
  • Electrostatic attractions (ionic bonds).
  • Hydrogen bonds.
  • Van der Waals attractions.
  • Hydrophobic force.
• Individual noncovalent attractions are weak but collectively create strong forces between molecules.
• These sets of attractions allow complementary macromolecule surfaces to bind (Figure 2-3).
• Water weakens electrostatic attractions and hydrogen bonds through competing interactions.
• Hydrogen bonds are directional, strongest when atoms align in a straight line (Figure 2-4).
• Hydrophobic force pushes nonpolar surfaces out of the water network, causing them to aggregate.

Acids and Bases in Water

• Molecules with polar covalent bonds between hydrogen and another atom can dissolve in water.
• The hydrogen atom loses its electron and becomes a proton (H+).
• Protons are attracted to the negative charge on the oxygen atom of water molecules, forming hydronium ions (H3O+) (Figure 2-5A).
• Acids release protons (H3O+) when dissolved in water.
• The concentration of H3O+ determines acidity.
• H3O+ concentration is expressed using the pH scale.
• Pure water is neutral with a pH of 7.0.
• The concentration of H3O+ inside a cell must be closely regulated.
• Bases accept protons from water molecules.
• Sodium hydroxide (NaOH) is a strong base.
• Weak bases reversibly accept protons from water, such as amino (NH2) groups.
  • $–NH<em>2 + H</em>2O \rightarrow –NH_3^+ + OH^–$
• Buffers maintain a stable pH by releasing or taking up protons near pH 7.

Carbon Compounds

• Cells are primarily based on carbon-containing molecules except for water and inorganic ions.
• Carbon can form four covalent bonds, creating chains, rings, and complex molecules.
• Organic molecules are carbon compounds made by cells.
• Specific chemical groups (methyl, hydroxyl, carboxyl, carbonyl, phosphate, sulfhydryl, and amino) influence molecular behavior.
• Cells have four major families of small organic molecules: sugars, fatty acids, nucleotides, and amino acids (Figure 2-6).
• These families account for a significant portion of cell mass.

Macromolecules

• Macromolecules are the most abundant carbon-containing molecules in cells (Figure 2-7).
• They are polymers of small organic molecules (monomers) linked by covalent bonds (Figure 2-8).
• Proteins serve as enzymes, structural components, and molecular motors.
• Polymer chains grow via condensation reactions, releasing water (Figure 2-9).
• Most macromolecules are made from a limited set of slightly different monomers.
• Monomers are added in a precise sequence, not randomly.

Noncovalent Bonds and Molecular Shape

• Covalent bonds in macromolecules allow for flexibility.
• Noncovalent bonds between different parts of a molecule constrain its shape.
• Sufficient noncovalent bonds lead to a preferred conformation determined by the monomer sequence.
• Proteins and small RNA molecules fold into preferred conformations (Figure 2-10).
• Noncovalent interactions:
  • Fold macromolecules.
  • Create strong attractions between molecules (Figure 2-3).
  • Provide specificity.
  • Allow rapid dissociation when needed.
• These interactions make biological catalysis possible.
• Macromolecules serve as building blocks for larger structures (Figure 2-11).

Catalysis and Energy Use

• Living things create and maintain order, contrasting with the universe's tendency toward disorder (Figure 2-12).
• Cells perform chemical reactions using small organic molecules.
• Specialized biological catalysts, usually enzymes, are proteins that accelerate reactions.
• Enzyme-catalyzed reactions are connected in series, forming metabolic pathways (Figure 2-13).
• Catabolic pathways break down food, generating energy and building blocks.
• Anabolic pathways use energy and building blocks to synthesize cell molecules.
• The two sets of reactions are metabolism (Figure 2-14).

Thermodynamics

• The second law of thermodynamics states that disorder (entropy) in an isolated system (or the universe) always increases.
• Cells generate order but are not isolated systems.
• They take in energy from their environment and release heat, increasing disorder in their surroundings.
• The first law of thermodynamics states that energy can be converted, but not created or destroyed (Figure 2-17).
• Cells convert chemical-bond energy from food into heat energy.
• Cells derive benefit from heat energy when heat-generating reactions are directly linked to generating molecular order.

Oxidation of Organic Molecules

• Animal and plant cells obtain energy from organic molecules through gradual oxidation or controlled burning.
• In the Earth's atmosphere, the most stable forms of carbon and hydrogen in the presence of oxygen are CO2 and H2O, respectively.
• Aerobic respiration is how cells obtain energy from sugars by combining carbon and hydrogen atoms with oxygen to produce CO2 and H2O.
• Photosynthesis and respiration are complementary processes (Figure 2-18).
• Carbon utilization forms a cycle involving the biosphere (Figure 2-19).

Oxidation and Reduction

• Oxidation is the removal of electrons, and reduction is the addition of electrons.
• Oxidation and reduction always occur simultaneously.
• The terms apply even when there is only a partial shift of electrons (Figure 2-20).
• Oxidation: when a carbon atom covalently bonds to an atom with a strong affinity for electrons.
• Reduction: a carbon atom in a C-H linkage has slightly more than its share of electrons.
  • $A + e^– + H^+ \rightarrow AH$
• Organic molecules are being oxidized if they increase the number of bonds to elements more electronegative than C, and are being reduced when their number of C-H bonds increases.

Enzymes and Activation Energy

• Molecules require activation energy to undergo chemical reactions.
• Enzymes lower the activation energy by binding to molecules (substrates) (Figure 2-21).
• Catalysts increase the rate of chemical reactions, and enzymes are highly effective catalysts (Figure 2-22).
• Enzymes cannot change the equilibrium point for reactions (Figure 2-23).
• Enzymes control reactions in cells, directing molecules along specific reaction paths (Figure 2-24).
• Each enzyme has a unique active site for particular substrates (Figure 2-25).

Molecular Motion

• Enzymes bind new substrate molecules quickly.
• Molecular motions, including:
  • Translational motion.
  • Vibrations.
  • Rotations, which are rapid at the molecular level.
• These motions help bring molecules together.
• Molecules move by diffusion, which is a random walk process (Figure 2-26).
• Inside cells diffusion occurs efficiently for small molecules (Figure 2-27).
• Encounter rate of enzymes with substrates depends on substrate concentration.

Free-Energy Change

• Enzymes cannot force unfavorable reactions.
• Cells couple favorable reactions to unfavorable reactions.
• Free energy (G) quantifies whether a reaction can occur spontaneously.
• The change in free energy (ΔG) measures the disorder created in the universe.
• Energetically, favorable reactions have a negative ΔG and increase disorder (Figure 2-28).
• Unfavorable reactions have a positive ΔG and create order.
• Unfavorable reactions are coupled to favorable reactions with a negative ΔG to drive the reactions (Figure 2-29).

Reactant Concentration

• For the reaction $Y \leftrightarrow X$, a large excess of Y over X will drive the reaction to $Y \rightarrow X$.
• As the ratio of Y to X increases, the ΔG becomes more negative for the transition $Y \rightarrow X$ (and more positive for the transition $X \rightarrow Y$ ).

Standard Free-Energy Change

• The change in free energy under a standard condition, defined as that where the concentrations of all the reactants are set to the same fixed value of 1 mole/liter.
  • $\Delta G = \Delta G° + RT \ln \frac{[X]}{[Y]}$
  • At 37°C, $RT = 2.58$. A mole is $6 × 10^{23}$ molecules of a substance.

Equilibrium Constants

• The ΔG equals the value of ΔG° when the concentrations of Y and X are equal.
• Equilibrium constant, K, for the reaction $Y \rightarrow X$ as:
  • $K = \frac{[X]}{[Y]}$
  • where [X] is the concentration of the product and [Y] is the concentration of the reactant at equilibrium.
• $\Delta G° = –RT \ln \frac{[X]}{[Y]} = –RT \ln K$
• At 37°C, where $RT = 2.58$, the equilibrium equation is:
  • $\Delta G° = –2.58 \ln K$
  • Converting this equation from the natural logarithm (ln) to the more commonly used base 10 logarithm (log), we get $\Delta G° = –5.94 \log K$
• For a reaction that has multiple reactants and products, such as $A + B \rightarrow C + D$,
  • $K = \frac{[C][D]}{[A][B]}$
  • $\Delta G° = –5.94 \log \frac{[C][D]}{[A][B]}$, where ΔG° is in kilojoules per mole, and [A], [B], [C], and [D] denote the concentrations of the reactants and products in moles/liter.

Reaction Coupling

• Favorable reactions can be coupled to unfavorable ones.
• The overall free-energy change for coupled reactions is the sum of the free-energy changes:
  • Example: For sequential reactions X \rightarrow Y (ΔG° = +5 kJ/mole) and Y \rightarrow Z (ΔG° = –13 kJ/mole), the coupled reaction ΔG° = –8 kJ/mole.
• Activated carrier molecules are often involved.

Activated Carrier Molecules

• Energy released during food molecule oxidation is stored temporarily in activated carrier molecules (Figure 2-31).
• These molecules contain energy-rich covalent bonds and diffuse rapidly throughout the cell.
• They serve as energy and chemical group sources in biosynthetic reactions.
• They are also called coenzymes.
• Examples: ATP, NADH, and NADPH.

Energy Coupling

• Coupling mechanisms with enzymes are fundamental to energy transactions.
• The energy of a favorable reaction (e.g., rocks falling) can drive an unfavorable reaction (e.g., lifting water), as shown in Figure 2-32.
• Released heat is reduced during this coupling.
• Enzymes couple oxidation of food to the generation of the activated carrier molecule.

ATP

• ATP (adenosine triphosphate) is the most important activated carrier (Figure 2-33).
• ATP is synthesized from ADP (adenosine diphosphate) and a phosphate group.
• ATP releases its energy through hydrolysis to ADP and inorganic phosphate.
• The energetically favorable reaction of ATP hydrolysis is coupled to many otherwise unfavorable reactions.
• ATP often transfers its terminal phosphate to another molecule (Figure 2-34).
• ATP supplies energy for transport and molecular motors.

Joining Molecules with ATP

• A biosynthetic reaction:
  • A–H + B–OH \rightarrow A–B + H2O
• Reaction pathway contains two steps:
  1. $B–OH + ATP \rightarrow B–O–PO_3 + ADP$
  2. $A–H + B–O–PO<em>3 \rightarrow A–B + P</em>i$
• Net result:
  • $B–OH + ATP + A–H \rightarrow A–B + ADP + P_i$
• The condensation reaction is coupled to ATP hydrolysis (Figure 2-35A).
• Glutamine is synthesized in this manner (Figure 2-35B).

Electron Carriers

• Activated carrier molecules participate in oxidation-reduction reactions.
• NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate) are essential electron carriers.
• They accept two electrons plus a proton (H+) to become NADH and NADPH, respectively (Figure 2-36). *NADPH
  • Is an electron donor and participates in biosynthesis.
  • Enzymes remove two H atoms from a substrate. Both electrons and one proton go to NADP+ to form NADPH; the other proton is released.
    • $NADP^+ + 2e^- + H^+ \rightarrow NADPH$
      *NAD+
  • The molecule NAD+ is nearly identically structured to NADP+, however, it lacks a phosphate group on one of the ribose-sugar rings. NAD+ has a special role as an intermediate in catabolic reactions.
• In the cell ratio of NAD+ is kept high, however, NADP+ ratio is kept low.
• NADPH gives up its hydride ion to another molecule, this subsequent reactions forms back NADP+ and reduces a substrate (Figure 2-37A).

Other Activated Carriers

• Coenzyme A carries an acetyl group in a thioester linkage, forming acetyl CoA (Figure 2-38).
• The transferable group is a small part of the molecule, with the large organic portion being a