Comprehensive Biochemistry: Biological Macromolecules, Enzyme Kinetics, and the Chemical Properties of Water

Carbon Chemistry and Hydrocarbons

• Importance of Carbon to Living Systems:

  • Carbon possesses $4$ valence electrons, enabling it to form $4$ strong, stable covalent bonds with other atoms.

  • Carbon atoms can bind covalently to one another, forming limitless carbon skeletons and branching chains.

  • Carbon can form single bonds ($C-C$), double bonds ($C=C$), or triple bonds ($C \equiv C$) with other atoms.

  • Organic Chemistry: The branch of chemistry dedicated to the scientific study of carbon-containing compounds.

• Hydrocarbons:

  • Compounds composed exclusively of carbon ($C$) and hydrogen ($H$) atoms.

  • Characterized by high flammability and high potential energy stored within carbon-hydrogen bonds.

  • Combustion Reaction of Hydrocarbons:     $\text{Hydrocarbon} + O_2 \rightarrow CO_2 + H_2O + \text{heat}$

  • Reactants: The starting chemical substances (ingredients) located on the left-hand side of the reaction arrow ($\text{Hydrocarbon} + O_2$).

  • Products: The substances produced by the chemical rearrangement, located on the right-hand side of the arrow ($CO_2 + H_2O + \text{heat}$).

• Representative Hydrocarbon Structures:

  • Methane ($CH_4$): Single central carbon bonded to four hydrogen atoms via single covalent bonds.

  • Acetylene ($C_2H_2$): Two carbon atoms joined by a carbon-carbon triple bond ($H-C \equiv C-H$).

  • Butadiene ($C_4H_6$): Four-carbon conjugated hydrocarbon containing two alternating carbon-carbon double bonds.

  • Benzene ($C_6H_6$): Six-carbon aromatic ring structure with alternating single and double carbon bonds.

  • Isooctane ($C_8H_{18}$): Branched eight-carbon alkane ($2,2,4\text{-trimethylpentane}$).

Macromolecular Polymers and Biochemical Reactions

• Polymer Concepts and Definitions:

  • Macromolecules: Large, highly organized biological polymers formed from linked subcomponents.

  • Polymer: Derived from the Greek roots poly ("many") and meros ("part"); a large molecule constructed by covalently linking smaller repeating units.

  • Monomer: A single molecular subcomponent or subunit that acts as the building block of a polymer chain.

• Dehydration Synthesis (Condensation):

  • Etymology: de = "delete" / remove; hydro = "water"; synthesis = "to put together".

  • Reaction mechanism: Joins two monomers covalently through the removal of a water molecule ($H_2O$).

  • One monomer donates a hydroxyl group ($-OH$) and the adjacent monomer donates a hydrogen atom ($-H$), forming a covalent bond between the subunits while eliminating $H_2O$.

• Hydrolysis:

  • Etymology: hydro = "water"; lysis = "to break" or split.

  • Reaction mechanism: Cleaves covalent bonds within a polymer chain by adding a water molecule ($H_2O$).

  • The water molecule is split: a hydrogen atom ($-H$) attaches to one monomer, and a hydroxyl group ($-OH$) attaches to the adjacent monomer, separating them.

• Elemental Distribution of the Four Primary Macromolecules:

  • All four classes of biological macromolecules (carbohydrates, lipids, proteins, nucleic acids) contain Carbon ($C$), Hydrogen ($H$), and Oxygen ($O$).

  • Proteins additionally contain Nitrogen ($N$) and sometimes Sulfur ($S$).

  • Nucleic acids contain Nitrogen ($N$) and Phosphorus ($P$), following the elemental acronym $\text{CHNOPS}$.

Carbohydrates: Structure, Classification, and Function

• Elemental Composition and Roles:

  • Contain Carbon ($C$), Hydrogen ($H$), and Oxygen ($O$).

  • Primary Functions:

  • Short-term, immediate cellular energy generation.

  • Structural support in cellular and organismal architecture.

• Monomer Unit:

  • Monosaccharide: Simple single-ring sugar unit (e.g., glucose, $C_6H_{12}O_6$).

• Carbohydrate Classes and Examples:

  • Simple Sugars:

  • Monosaccharides: Glucose.

  • Disaccharides: Sucrose (table sugar, a disaccharide of glucose and fructose linked by a glycosidic bond) and lactose (milk sugar).

  • Dietary Starches: Plant energy storage polysaccharides found in foods such as bread, pasta, and rice.

  • Starch Polymer Subtypes:

  • Amylose: Unbranched, linear polymer composed of repeating glucose residues linked via $\alpha\text{-}1,4\text{-glycosidic}$ bonds.

  • Amylopectin: Branched plant glucose polymer featuring linear chains with periodic $\alpha\text{-}1,6$ branch linkages.

  • Complex Biological Polymers:

  • Glycogen: Heavily branched glucose storage polysaccharide found in animal liver and skeletal muscle.

  • Cellulose: Structural polysaccharide composed of rigid glucose chains forming plant cell walls.

Lipids: Energy Storage, Cellular Membranes, and Signaling

• Elemental Composition and General Traits:

  • Composed predominantly of Carbon ($C$) and Hydrogen ($H$), with a small proportion of Oxygen ($O$).

  • Hydrophobic, nonpolar molecules insoluble in aqueous solutions.

  • Key Biological Functions:

  • High-density, long-term cellular energy storage.

  • Thermal insulation and mechanical protection of vital organs.

  • Structural foundation of biological cell membranes.

  • Endocrine signaling molecules and chemical messengers.

  • Common Examples: Butter, grease, cooking oils, and steroids.

• Structural Components (Building Blocks):

  • Constructed from a glycerol backbone and fatty acid hydrocarbon tails.

• Three Primary Classes of Lipids:

  • Triglycerides:

  • Formed from one glycerol molecule covalently bound to three fatty acid chains via ester bonds.

  • Fatty acids can be saturated (single carbon-carbon bonds, straight hydrocarbon tails, packed densely) or unsaturated (contain one or more $C=C$ double bonds that introduce bends/kinks into the chain).

• Phospholipids:

  • Composed of a glycerol backbone linked to two nonpolar, hydrophobic fatty acid tails and one negatively charged, polar, hydrophilic phosphate head group.

  • In aqueous environments, phospholipids spontaneously orient into a phospholipid bilayer, creating cell membranes where hydrophobic tails face inward and hydrophilic heads face the intra- and extracellular fluids.

• Steroids:

  • Lipids characterized by a rigid carbon skeleton consisting of four fused rings ($3$ six-carbon rings and $1$ five-carbon ring).

  • Cholesterol: A foundational steroid (containing numbered carbon positions $1$ through $27$) essential for modulating membrane fluidity and serving as a biochemical precursor for steroid hormones.

Proteins: Structure, Classification, and Cellular Functions

• Elemental Composition and General Roles:

  • Composed of Carbon ($C$), Hydrogen ($H$), Oxygen ($O$), and Nitrogen ($N$).

  • Monomer units: Amino Acids.

  • Cellular Functions:

  • Structural architecture (e.g., muscle fibers, insect exoskeletons, keratin in hair and fingernails).

  • Biological catalysis (enzymes accelerating biochemical reactions).

  • Gas and nutrient transport (e.g., hemoglobin delivering oxygen in red blood cells).

  • Intercellular communication, signal transduction, and cell recognition via membrane proteins.

  • Immune protection (e.g., antibodies).

• Membrane Protein Classifications:

  • Single-pass integral proteins: Polypeptides that span the lipid bilayer once.

  • Multi-pass integral proteins: Polypeptides that weave through the lipid bilayer multiple times.

  • Monotropic proteins: Membrane proteins associated with only one leaflet/side of the lipid bilayer.

  • Extrinsic (peripheral) proteins: Proteins attached non-covalently to the membrane surface.

• Contractile Proteins:

  • Muscle contraction relies on interacting filaments of Actin and Myosin, regulated by Tropomyosin and Troponin.

• Amino Acid Architecture:

  • The human body uses $20$ distinct amino acids to construct polypeptides.

  • Universal Amino Acid Structure:

  • A central alpha-carbon ($C_\alpha$).

  • A hydrogen atom ($-H$).

  • An amino group ($-NH_2$ or protonated as $-NH_3^+$).

  • A carboxyl group ($-COOH$ or ionized as $-COO^-$).

  • A variable side chain ($R$ group) that dictates chemical properties.

• The 20 Amino Acids Classified by Side Chain Characteristics:

  • Nonpolar Side Chains:

  • Glycine (Gly / G)

  • Alanine (Ala / A)

  • Valine (Val / V)

  • Leucine (Leu / L)

  • Isoleucine (Ile / I)

  • Methionine (Met / M)

  • Phenylalanine (Phe / F)

  • Tryptophan (Trp / W)

  • Proline (Pro / P)

  • Polar Side Chains:

  • Serine (Ser / S)

  • Threonine (Thr / T)

  • Cysteine (Cys / C)

  • Tyrosine (Tyr / Y)

  • Asparagine (Asn / N)

  • Glutamine (Gln / Q)

  • Electrically Charged Side Chains - Acidic:

  • Aspartate (Asp / D)

  • Glutamate (Glu / E)

  • Electrically Charged Side Chains - Basic:

  • Lysine (Lys / K)

  • Arginine (Arg / R)

  • Histidine (His / H)

• Peptide Bond Formation:

  • Individual amino acids link together covalently via peptide bonds.

  • Formed via dehydration synthesis between the carboxyl carbon ($-C=O$) of one amino acid and the amino nitrogen ($-NH-$) of another, releasing $H_2O$.

  • Polymers of amino acids linked by peptide bonds are called polypeptides.

• Four Hierarchical Levels of Protein Structure:

  • Primary Structure: The unique linear sequence of amino acids in a polypeptide chain.

  • Secondary Structure: Regular, localized folding patterns within the polypeptide backbone stabilized by hydrogen bonds between amino and carboxyl groups, forming $\alpha$-helices and $\beta$-pleated sheets.

  • Tertiary Structure: The complete three-dimensional folding of a single polypeptide chain, driven by hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bridges among $R$ groups (e.g., a single $\beta$ polypeptide subunit with an embedded heme group).

  • Quaternary Structure: The spatial arrangement and association of two or more polypeptide chains into a functional multisubunit protein complex (e.g., functional hemoglobin composed of two $\alpha$ and two $\beta$ polypeptide chains).

Nucleic Acids: Information Storage and Transmission

• Elemental Composition and Primary Roles:

  • Composed of Carbon ($C$), Hydrogen ($H$), Nitrogen ($N$), Oxygen ($O$), and Phosphorus ($P$).

  • Functions:

  • Store and transmit hereditary genetic information across generations.

  • Provide precise molecular instructions for synthesizing cellular proteins.

• Monomer Unit: The Nucleotide:

  • Composed of three distinct chemical components:

  1. A five-carbon pentose sugar (deoxyribose in DNA, ribose in RNA).

  2. A negatively charged phosphate group.

  3. A nitrogenous base (Adenine, Thymine, Guanine, Cytosine, or Uracil).

• Major Nucleic Acid Types:

  • DNA (Deoxyribonucleic Acid):

  • Double-stranded anti-parallel helix.

  • Contains a sugar-phosphate backbone linked by phosphodiester bonds.

  • Nitrogenous bases project inward and form complementary base pairs:

    • Adenine ($A$) pairs with Thymine ($T$).

    • Guanine ($G$) pairs with Cytosine ($C$).

  • RNA (Ribonucleic Acid):

  • Typically single-stranded.

  • Contains ribose sugar and nucleobases (with Uracil replacing Thymine).

Enzyme Catalysis, Kinetics, and Models of Action

• Enzymatic Catalysis Principles:

  • Enzymes are proteins functioning as biological catalysts.

  • Catalysts accelerate the rate of chemical reactions without being consumed, degraded, or permanently altered during the reaction.

  • Biochemical reactions catalyzed by enzymes occur naturally, but without an enzyme, their spontaneous rates are far too slow to sustain cellular life.

  • Enzymes are reusable across repeated catalytic cycles.

  • Enzymes exhibit substrate specificity: a given enzyme typically acts on only $1$ specific substrate.

  • Enzyme functionality depends strictly on its unique three-dimensional conformation.

• Thermodynamic Basis: Activation Energy:

  • Activation Energy ($E_a$): The initial threshold of energy required to destabilize existing chemical bonds and initiate a reaction, driving reactants to an unstable transition state (activated complex).

  • Enzymes accelerate reactions by lowering the activation energy barrier ($E_a$).

  • Enzymes do not change the initial potential energy of reactants or the final potential energy of products.

• The Active Site and Substrate Interaction:

  • Substrate: The specific reactant molecule upon which an enzyme acts.

  • Active Site: A specialized catalytic pocket or groove formed by amino acid side chains on the enzyme's surface where the substrate binds.

  • Binding yields an intermediate Enzyme-Substrate Complex ($ES$ complex).

• Models of Enzyme-Substrate Binding:

  • Lock and Key Model:

  • Proposes that the enzyme's active site and the substrate have complementary geometric shapes that fit together rigidly and precisely from the start, analogous to a key fitting into a lock.

• Induced Fit Model:

  • Proposes that the initial binding of the substrate induces a conformational shift in the enzyme.

  • The active site adjusts its shape slightly around the substrate to maximize binding affinity and catalyze bond making or breaking.

• Reaction Pathways Catalyzed by Enzymes:

  • Catabolic Reaction (Decomposition/Breakdown):

  1. Substrate enters the complementary active site of the enzyme.

  2. Enzyme-substrate complex forms, with the enzyme shifting shape slightly via induced fit.

  3. Bonds within the substrate are broken, converting substrate into distinct products.

  4. Products leave the active site, leaving the unaltered enzyme ready to receive another substrate.

• Anabolic Reaction (Synthesis/Building Up):

  1. Multiple distinct substrates enter the active site of the enzyme.

  2. Enzyme-substrate complex forms.

  3. New chemical bonds are formed between the substrates (often eliminating $H_2O$ via dehydration synthesis).

  4. The consolidated, newly formed product molecule departs the active site.

• Factors Influencing Enzymatic Rates and Denaturation:

  • pH Range:

  • Most human enzymes exhibit optimal catalytic efficiency at a pH between $6$ and $8$ (near-neutral physiological pH).

  • Specialized exceptions exist: digestive enzymes in the stomach (e.g., pepsin) function optimally under highly acidic conditions ($\text{pH} \approx 1.5 - 2$).

  • Deviation from an enzyme's optimal pH alters amino acid ionization, disrupting tertiary structure and causing denaturation (loss of catalytic shape and activity).

  • Temperature Range:

  • The optimal temperature for most human enzymes ranges from $35^\circ\text{C}$ to $40^\circ\text{C}$ (encompassing normal physiological body temperature of approximately $37^\circ\text{C}$).

  • Temperatures elevated above this optimum disrupt the non-covalent interactions maintaining protein structure, causing thermal denaturation.

• Key Representative Enzymes and Functions:

  • Many enzyme names are designated with the suffix -ase.

  • Amylase: Catalyzes the breakdown of starches into smaller carbohydrates.

  • Sucrase: Hydrolyzes sucrose into glucose and fructose.

  • Lactase: Hydrolyzes lactose into glucose and galactose.

  • Pepsin: Active stomach protease that breaks down dietary proteins into peptides at acidic pH.

  • Bromalin: Proteolytic enzyme found in fruits (e.g., pineapples) that hydrolyzes protein bonds.

  • Peroxidase: Catalyzes the decomposition of toxic hydrogen peroxide into water and oxygen.

Properties of Water and Aqueous Systems

• Molecular Structure and Polarity:

  • Consists of two Hydrogen atoms covalently bound to one central Oxygen atom ($H_2O$).

  • Covalent electrons are shared unequally due to the higher electronegativity of oxygen.

  • This unequal electron distribution creates a polar molecule:

  • Oxygen bears a partial negative charge ($\delta^-$).

  • Hydrogens bear partial positive charges ($\delta^+$).

• Hydrogen Bonding:

  • The partial negative oxygen of one water molecule electrostatically attracts the partial positive hydrogen of an adjacent water molecule.

  • Weak individually, but massive networks of transient hydrogen bonds give water its emergent properties.

• The Universal Solvent:

  • Water readily dissolves ionic compounds and polar solutes (including carbohydrates and many proteins).

  • Water cannot dissolve nonpolar lipids, which are hydrophobic.

  • Its solvent capabilities provide the aqueous cytosol and interstitial fluid required for cellular metabolism.

• Cohesion, Adhesion, and Surface Tension:

  • Cohesion: The tendency of water molecules to stick to one another via hydrogen bonding.

  • Adhesion: The attractive force between water molecules and other polar or charged surfaces.

  • Surface Tension: Strong cohesive forces at the air-water interface produce high surface tension, allowing water to behave as if coated by an elastic film. This enables denser organisms (such as water striders) to walk across water without sinking.

• Capillary Action:

  • Arises from the combined actions of adhesion and cohesion.

  • Water adheres to polar surfaces (such as cellulose or glass walls) while cohesive forces pull upward adjacent water molecules.

  • This enables water to move against gravity through microscopic tubes (such as xylem vessels in plants).

• Density Anomaly of Water as a Solid:

  • Water expands upon freezing rather than contracting.

  • As temperatures drop below $4^\circ\text{C}$, water molecules lock into an open, hexagonal crystal lattice maintained by rigid hydrogen bonds, holding molecules further apart than in liquid state.

  • Solid ice is less dense than liquid water, allowing it to float on lakes and rivers and insulating the aquatic life below during winter.

• High Specific Heat Capacity:

  • Water requires a large amount of heat energy to raise its temperature, because heat is first absorbed to break hydrogen bonds before kinetic energy can rise.

  • Water resists rapid temperature fluctuations, moderating terrestrial climates and helping organisms maintain internal thermal homeostasis.

• High Heat of Vaporization and Evaporative Cooling:

  • Significant heat energy is required to break hydrogen bonds and convert liquid water into water vapor.

  • Evaporative Cooling: As water evaporates from a surface, the highest-energy (hottest) molecules leave, cooling the remaining surface. This is the physiological mechanism behind cooling via sweat evaporation from human skin.

The pH Scale and Acid-Base Equilibrium

• Definition of pH:

  • A mathematical scale that measures the molar concentration of hydrogen ions ($[H^+]$) in an aqueous solution.

  • Square brackets ($[\ ]$) denote concentration.

• Water Dissociation Equilibrium:   $[H^+] + [OH^-] \rightleftharpoons H_2O$

  • Pure water dissociates equally into hydrogen ions ($[H^+]$) and hydroxide ions ($[OH^-]$).

  • In pure water, $[H^+] = [OH^-]$, corresponding to a neutral pH of exactly $7$.

• Acids and Bases:

  • Acid:

  • A solution with a higher concentration of $[H^+]$ ions than pure water ($[H^+] > [OH^-]$).

  • Possesses a pH value below $7$ ($\text{pH} < 7$).

  • Base (Alkaline):

  • A solution with a lower concentration of $[H^+]$ ions (and higher concentration of $[OH^-]$ ions) than pure water ($[H^+] < [OH^-]$).

  • Possesses a pH value above $7$ ($\text{pH} > 7$).

• The pH Scale and Everyday Examples ($0$ to $14$):

  • $\text{pH} = 0$: Battery acid

  • $\text{pH} = 1$: Stomach acid

  • $\text{pH} = 2$: Lemon juice

  • $\text{pH} = 3$: Vinegar

  • $\text{pH} = 4$: Tomato juice

  • $\text{pH} = 5$: Black coffee

  • $\text{pH} = 6$: Milk

  • $\text{pH} = 7$: Pure water (Neutral)

  • $\text{pH} = 8$: Human blood

  • $\text{pH} = 9$: Baking soda

  • $\text{pH} = 10$: Stomach antacid tablets

  • $\text{pH} = 11$: Ammonia cleaning solution

  • $\text{pH} = 12$: Hand soap

  • $\text{pH} = 13$: Bleach

  • $\text{pH} = 14$: Liquid drain cleaner