The Chemical Basis of Life II: Organic Molecules

3.1 The Carbon Atom

  • Learning outcomes
    • Explain the properties of carbon that make it the chemical basis of all life.
    • Describe the variety and chemical characteristics of common functional groups of organic compounds.
    • Compare and contrast different types of isomers.
  • The science of carbon-containing molecules
    • Organic chemistry deals with carbon-containing molecules found in living organisms.
    • A long-standing debate centered on vitalism: the idea that organic molecules required a “vital life force.”
    • Vitalism was challenged and disproved by Friedrich Wöhler, who synthesized an organic compound (urea) from inorganic precursors, showing no life force was needed.
    • Wöhler’s classic observation: ammonium cyanate (NH2OCN) reacts with ammonia to yield urea ((NH2)2CO) upon heating, revealing that organic molecules can arise from inorganic chemistry.
    • Other chemists (e.g., Hermann Kolbe) extended these insights to synthesize other organic compounds directly from simple inorganic building blocks.
  • Central role of carbon in organic chemistry
    • The carbon atom forms bonds with itself and with H, O, N, S, etc., creating a vast diversity of molecules from a small set of elements.
    • The carbon atom forms four covalent bonds, enabling tetravalence and a wide array of structures.
  • Carbon forms four covalent bonds with other atoms
    • Carbon has four electrons in its outer (second) shell and needs eight electrons to complete the shell, promoting four covalent bonds to reach a stable configuration.
    • Carbon commonly bonds with C, H, O, N, and S in biological molecules; bonds can be single, double, or triple (e.g., C–C, C–O, C=C, C≡N).
    • Bond types influence solubility and polarity:
    • C–C and C–H bonds are nonpolar and electrically neutral.
    • Bonds to more electronegative atoms (C–O, C=O, C–N) are polar and increase water solubility due to interactions with polar water.
    • The ability of carbon to form both polar and nonpolar bonds allows it to serve as the backbone for a huge variety of biologically important molecules.
  • Carbon forms bonds of varying stability across life’s temperature range
    • Carbon–carbon bonds are relatively short, contributing to bond strength and stability across environmental temperatures.
    • This stability helps life persist from polar cold to deep-sea heat.
  • Carbon-containing molecules may include functional groups
    • Functional groups are atom clusters with characteristic properties that influence molecule chemistry (e.g., amino, carbonyl, hydroxyl, phosphate).
    • A representative list (Table 3.1) includes:
    • Amino (-NH2): weakly basic; polar; part of peptide bonds; found in amino acids and proteins.
    • Carbonyl (-CO) / Ketone: polar; reactive; present in steroids, waxes, and proteins.
    • Aldehyde (-CHO): polar; reactive; present in many small molecules.
    • Carboxyl (-COOH): acidic; present in amino acids and fatty acids; part of peptides.
    • Hydroxyl (-OH): polar; forms hydrogen bonds; present in alcohols, sugars.
    • Methyl (-CH3): nonpolar; impacts hydrophobicity; present in many organic molecules.
    • Phosphate (-PO4^2-): polar; often attached to DNA, proteins, carbohydrates; influences acidity and charge.
    • Sulfate (-SO4^2-): polar; negatively charged at cellular pH; attached to carbohydrates and proteins.
    • Sulfhydryl (-SH): polar; forms disulfide bridges in proteins (stabilizes structure).
    • R and R′ denote the remainder of the molecule.
  • Carbon-containing molecules may exist as isomers
    • Isomers have the same chemical formula but different structures and properties.
    • Structural isomers: same atoms, different bonding relationships (e.g., isopropyl alcohol vs propyl alcohol).
    • Stereoisomers: same bonding relationships but different spatial arrangement. Two main types:
    • Cis–trans isomers: difference in orientation around a C=C double bond (cis has substituents on same side; trans on opposite sides).
      • Example relevance: retinal in the eye shifts from cis to trans upon light exposure, enabling vision.
    • Enantiomers: non-superimposable mirror images (left/right-handed). Four different substituents can yield two enantiomers for a chiral carbon.
      • Enantiomers have identical chemical properties but can differ in their noncovalent interactions (e.g., enzyme binding).
  • Monomers, polymers, and macromolecules
    • Most organic molecules form larger assemblies by linking monomers into polymers via dehydration (condensation) reactions, releasing a water molecule for each bond formed.
    • Dehydration reaction: monomer + monomer → polymer + H2O
    • Polymers can be hydrolyzed back into monomers by hydrolysis, adding water to break bonds.
    • DNA synthesis and other macromolecule formation rely on dehydration reactions to build long polymers from monomers.

3.2 Formation of Organic Molecules and Macromolecules

  • Dehydration (condensation) reactions build polymers by removing water for each new monomer added
    • Example mechanism shown in polymerization: two monomers join, water is removed, and an elongating polymer grows.
  • Hydrolysis reactions reverse polymer formation by adding water to break bonds
  • Implication: macromolecules range from small sugars to giant DNA, proteins, and more, assembled from monomers via dehydration and reversed via hydrolysis

3.3 Overview of the Four Major Classes of Organic Molecules Found in Living Cells

  • Four major classes (Table 3.2): carbohydrates, lipids, proteins, nucleic acids
  • Each class has characteristic structures, properties, and functions, and together they form the basis of cellular life
  • Central idea: all life uses a finite set of building blocks to construct a huge diversity of molecules

3.4 Carbohydrates

  • General features
    • Carbohydrates are carbon-containing compounds with the general formula extC(H<em>2extO)</em>next{C(H}<em>2 ext{O)}</em>n (often written as extC<em>n(extH</em>2extO)next{C}<em>n( ext{H}</em>2 ext{O})_n).
    • Most carbon atoms in carbohydrates are linked to hydrogen and a hydroxyl group; some may bear amino or carboxyl groups.
  • Sugars and polymers
    • Sugars are small carbohydrates; sugars can be classified as monosaccharides, disaccharides, or polysaccharides.
    • Monosaccharides: simplest sugars; common pentoses (five carbons) like ribose (C5H10O5) and deoxyribose (C5H10O4) and common hexoses (six carbons) like glucose (C6H12O6).
    • Glucose (the most common hexose): extC<em>6extH</em>12extO6ext{C}<em>6 ext{H}</em>{12} ext{O}_6; very water-soluble; circulates in bodily fluids; enzymatic breakdown yields energy stored in bonds, ultimately powering ATP production (see Chapter 7).
    • Ring versus linear forms: glucose can exist in linear form or ring form, with ring formation involving the oxygen from carbon 5 bonding to carbon 1. Ring forms are predominant in solution; ring carbons are numbered in standard convention.
    • Isomerism among monosaccharides: D- vs L- forms; α- vs β- anomers (anomeric configuration at carbon 1): e.g., D-glucose is the form most common in cells; α- and β- forms differ in the orientation of the -OH group on carbon 1.
  • Linking monosaccharides: dehydration reactions form glycosidic bonds
    • Disaccharides: two monosaccharides linked by a glycosidic bond; common examples include:
    • Sucrose: glucose + fructose; major transport sugar in plants; glycosidic linkage type is typically an α/β combination depending on the monomers.
    • Maltose: glucose + glucose; α-1,4-glycosidic linkage (commonly produced during digestion of starch).
    • Lactose: galactose + glucose; β-1,4-glycosidic linkage.
  • Polysaccharides: polymers of monosaccharides
    • Starch and glycogen: polymers of α-D-glucose; main energy storage polysaccharides in plants (starch) and animals (glycogen).
    • Linkages: α-1,4-glycosidic bonds; starch is less branched and less soluble than glycogen, which has extensive α-1,6 branches.
    • Function: store energy; hydrolyzed to release monosaccharides when needed for ATP production.
    • Cellulose: polymer of β-D-glucose; linear chains with β-1,4 linkages; every other glucose is flipped; forms parallel hydrogen-bonded sheets; extremely strong structural component of plant cell walls; not digestible by most animals due to β-linkage; certain bacteria possess cellulases; humans lack cellulases, hence dietary fiber.
    • Other structural polysaccharides: chitin (insect exoskeletons and fungal cell walls; nitrogen-containing monomers), glycosaminoglycans (cartilage and extracellular matrix).

3.5 Lipids

  • General features
    • Lipids are hydrophobic (nonpolar) molecules rich in carbon and hydrogen with some oxygen; they are insoluble in water.
    • Major classes include fats (triglycerides), phospholipids, steroids, and waxes.
  • Triglycerides (fats)
    • Structure: glycerol backbone (three-carbon molecule with one -OH on each carbon) attached to three fatty acids via ester bonds.
    • Formation: glycerol + 3 fatty acids → triglyceride + 3 H2O (dehydration reactions form three ester bonds).
    • Fatty acids: hydrocarbon chains with a terminal carboxyl group (-COOH).
    • Variability:
    • Length: most fatty acids have even numbers of carbons, commonly 16 or 18 (C16–C18).
    • Saturation: saturated fatty acids have only single C–C bonds; unsaturated fatty acids contain one or more C=C double bonds.
    • Cis/trans geometry: most natural unsaturated fatty acids are in the cis form; some artificially produced fats contain trans double bonds (trans fats).
    • Physical properties and health implications:
    • Saturated fats pack tightly, have high melting points, and are often solid at room temperature (e.g., beef fat contains stearic acid; melting point ~70°C).
    • Unsaturated fats have kinks due to double bonds, preventing tight packing; typically lower melting points and are liquids at room temperature (e.g., olive oil rich in oleic acid).
    • Trans fats (from hydrogenation) have higher melting points and are linked to cardiovascular disease.
  • Energy storage
    • Fats store more energy per gram than carbohydrates because of a higher density of C–H bonds.
    • They serve as long-term energy reserves in mobile organisms and provide insulation and cushioning.
  • Phospholipids: amphipathic lipids essential for membranes
    • Structure: glycerol backbone with two fatty acid tails (nonpolar) and a phosphate-containing head group (polar); a small, often charged molecule (e.g., choline) is attached to the phosphate, creating a polar (hydrophilic) head and two nonpolar (hydrophobic) tails.
    • In water, phospholipids form bilayers with heads facing water and tails inward, creating the basic structure of cellular membranes (the phospholipid bilayer).
  • Steroids
    • Structure: four fused hydrocarbon rings (cyclopentane-perhydro-phenanthrene skeleton) forming a rigid core.
    • Variations in functional groups yield diverse biologically active molecules (e.g., cholesterol, steroid hormones like estrogen and testosterone).
    • Small differences in structure can lead to large differences in function (e.g., estrogen vs. testosterone differences drive sexual differentiation).
  • Waxes
    • Complex, highly nonpolar lipids consisting of long hydrocarbon chains; they repel water and provide protective barriers to reduce water loss; also used structurally (e.g., beeswax on honeycombs, plant surfaces).

3.6 Proteins

  • General features and significance
    • Proteins are large, diverse macromolecules composed mainly of C, H, O, N, and S; they account for roughly 50% of organic material in animals.
    • Proteins are polymers of amino acids linked by peptide bonds and folded into precise three-dimensional shapes that determine their function.
  • Amino acids: the building blocks of proteins
    • Structure: an α-carbon bonded to an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom, and a side chain (R).
    • In aqueous solution at neutral pH, amino groups tend to be protonated (NH3+) and carboxyl groups deprotonated (COO−), giving amino acids their zwitterionic character.
    • The 20 standard amino acids differ in their side chains (R groups), which drive protein folding and function (e.g., hydrophobic vs. polar vs. charged side chains).
    • Stereochemistry: all amino acids (except glycine) have D- and L- enantiomers; proteins use only L-amino acids; some bacteria use D-amino acids in their cell walls.
  • Classification of amino acid side chains
    • Nonpolar (hydrophobic): e.g., Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, Trp (some exceptions like Tyr see note below).
    • Polar, uncharged: e.g., Ser, Thr, Asn, Gln, Tyr, Cys.
    • Polar, charged (acidic): Asp, Glu.
    • Polar, charged (basic): His, Lys, Arg.
  • Peptides, polypeptides, and proteins
    • Peptide bonds: formed when the carboxyl group of one amino acid reacts with the amino group of the next, releasing a molecule of water.
    • Polypeptide: a linear chain of amino acids linked by peptide bonds.
    • Protein: one or more polypeptides that fold into a functional three-dimensional structure; many proteins are glycosylated (glycoproteins) or lipoproteins with attached carbohydrates or lipids.
  • Protein structure: four hierarchical levels
    • Primary structure: the linear sequence of amino acids in a polypeptide; encoded by genes.
    • Secondary structure: local folding patterns stabilized by hydrogen bonds along the backbone; main forms are:
    • α-helix: right-handed helix stabilized by hydrogen bonds between the N−H of one amino acid and the C=O of another four residues away.
    • β-pleated sheet: strands running adjacent, connected by hydrogen bonds forming a zigzag sheet.
    • Tertiary structure: the overall three-dimensional shape of a single polypeptide, determined by interactions among side chains (R groups) including hydrogen bonds, ionic bonds, hydrophobic interactions, van der Waals forces, and disulfide bridges.
    • Quaternary structure: assembly of two or more polypeptides (subunits) into a functional protein (e.g., hemoglobin with four subunits).
  • Factors influencing protein folding and stability
    • Hydrogen bonds: numerous weak bonds create secondary structure and contribute to overall stability.
    • Ionic bonds and other polar interactions: between oppositely charged side chains; important for tertiary/quaternary structure.
    • Hydrophobic effect: nonpolar side chains cluster in the protein interior to minimize water exposure; also helps anchor proteins in membranes.
    • van der Waals dispersion forces: influence packing and stability of close-contact regions.
    • Disulfide bridges: covalent S−S bonds between cysteine residues stabilize or link parts of a protein.
  • Protein interactions and domains
    • Many proteins contain functional domains—modular units that have specific structures and functions and are conserved across proteins.
    • Example: nuclear receptors with four or more domains:
    • Ligand-binding domain: binds steroid hormones (e.g., estrogen or testosterone).
    • DNA-binding domain: binds DNA and regulates gene transcription.
    • Nuclear localization domain: directs movement into the nucleus.
    • Activation domain: activates transcription of target genes.
    • Domains can be rearranged during evolution, leading to new protein functions with similar modular architectures.
  • Anfinsen’s classic demonstration: primary structure determines tertiary structure
    • Hypothesis: the amino acid sequence contains all information needed for proper folding.
    • Experiment: ribonuclease (RNase) with four disulfide bridges was denatured using β-mercaptoethanol (breaks disulfide bonds) and urea (disrupts hydrogen/ionic bonds).
    • Result: RNase lost activity when denatured, but activity was restored after removing denaturants and allowing refolding, demonstrating that the primary sequence can determine the three-dimensional structure in many cases.
    • Impact: supported the central role of primary structure in protein folding; won Nobel Prize (1972).
  • Functional domains and evolution
    • Many proteins are built from repeating domains; domains can be shuffled or duplicated, giving rise to new proteins with diverse functions while retaining modular architecture.
  • Concept checks and applications
    • Enzymes often recognize specific enantiomers due to stereospecific binding; small changes in amino acid sequence can alter substrate binding and function.

3.7 Nucleic Acids

  • Nucleic acids and their roles
    • Nucleic acids store, transmit, and express genetic information.
    • DNA stores genetic information; RNA decodes information to synthesize proteins.
  • Nucleotides: building blocks of DNA and RNA
    • Each nucleotide has three components:
    • Phosphate group
    • Five-carbon sugar: deoxyribose in DNA; ribose in RNA
    • Nitrogenous base (a purine or pyrimidine)
    • Nucleotides are linked to form nucleic acid polymers via phosphodiester bonds between the 3′ carbon of one sugar and the 5′ carbon of the next.
  • DNA structure and base pairing
    • DNA is a double helix composed of two strands.
    • Strands run antiparallel: one 5′→3′, the other 3′→5′.
    • Bases pair via hydrogen bonds: A pairs with T (2 H-bonds); G pairs with C (3 H-bonds).
    • The base composition follows Chargaff’s rules: in any DNA sample, percentage of A equals T, and percentage of G equals C. If one base fraction is known, the others can be inferred (e.g., if G = 30%, then C = 30%, A = T = 20%).
  • RNA structure
    • Generally single-stranded; sugar is ribose; thymine is replaced by uracil (U) which pairs with adenine (A).
  • Visualizing nucleotides and backbones
    • Nucleotide example: a nucleotide consists of phosphate, sugar, and base (examples shown for deoxyribonucleotide and ribonucleotide).
    • DNA backbone: alternating sugar and phosphate groups with bases projecting inward to pair with the opposite strand.
  • Summary relationships among the four major classes and nucleic acids
    • DNA: double-stranded, deoxyribose, bases A/T and G/C pairings; stores genetic information.
    • RNA: usually single-stranded, ribose, base U instead of T; decodes and transmits information to synthesize proteins.

Summary of Key Concepts

  • The Carbon Atom and Organic Molecules
    • Organic chemistry focuses on carbon-containing molecules essential for life.
    • Carbon’s tetravalence enables formation of four covalent bonds, creating diverse molecular architectures.
    • Carbon–carbon and carbon–hydrogen bonds are nonpolar; bonds to more electronegative atoms (C–O, C=O, C–N) are polar and increase water solubility.
    • Carbon bonds remain stable across the temperature ranges organisms experience.
    • Functional groups confer characteristic chemical properties to molecules.
    • Isomers (structural and stereoisomers) provide structural and functional diversity from the same formula.
  • Formation of Organic Molecules and Macromolecules
    • Monomers link to form polymers via dehydration (condensation) reactions, releasing water.
    • Polymers can be broken down by hydrolysis, adding water back in.
  • Four Major Classes of Organic Molecules
    • Carbohydrates: energy and structural roles; monosaccharides, disaccharides, polysaccharides; energy storage (starch, glycogen) and structural roles (cellulose, chitin).
    • Lipids: nonpolar, energy-rich molecules (fats/triglycerides); phospholipids form cell membranes; steroids (cholesterol and hormones); waxes.
    • Proteins: amino acids form polypeptides; structure and function determined by sequence and folding into four structural levels (primary, secondary, tertiary, quaternary); domains enable modular functions; protein folding driven by multiple intramolecular forces; Anfinsen’s experiments highlighted the primacy of the primary structure in folding.
    • Nucleic Acids: DNA and RNA; nucleotides with phosphate, sugar, and base; base pairing rules (A–T, G–C in DNA; A–U in RNA); DNA double helix with antiparallel strands.
  • Form and Function in Biology
    • Structure determines function: the arrangement of atoms, bonds, and folds dictates biological roles of carbohydrates, lipids, proteins, and nucleic acids.
    • The modular nature of proteins (domains) and the specific interactions among molecules enable complex cellular processes and regulation.

Practice and Review

  • Key reaction forms to remember
    • Dehydration synthesis (condensation): monomer + monomer → polymer + H2O
    • Hydrolysis: polymer + H2O → monomer fragments
    • Peptide bond formation: amino acid + amino acid → dipeptide + H2O
    • Triglyceride formation: glycerol + 3 fatty acids → triglyceride + 3 H2O
  • Important formulas
    • Carbohydrates general formula: extC(H<em>2extO)</em>next{C(H}<em>2 ext{O)}</em>n
    • Glucose: extC<em>6extH</em>12extO6ext{C}<em>6 ext{H}</em>{12} ext{O}_6
    • Dehydration polymerization (generic): extMonomer<em>1+extMonomer</em>2<br/>ightarrowextPolymer+extH2extOext{Monomer}<em>1 + ext{Monomer}</em>2 <br /> ightarrow ext{Polymer} + ext{H}_2 ext{O}
    • Hydrolysis (generic): extPolymer+extH<em>2extOightarrowextMonomer</em>1+extMonomer2+ext…ext{Polymer} + ext{H}<em>2 ext{O} ightarrow ext{Monomer}</em>1 + ext{Monomer}_2 + ext{…}
    • Triglyceride formation: extGlycerol+3imesextFattyAcids<br/>ightarrowextTriglyceride+3extH2extOext{Glycerol} + 3 imes ext{Fatty Acids} <br /> ightarrow ext{Triglyceride} + 3 ext{H}_2 ext{O}
  • Key distinctions to recall
    • Saturated vs. unsaturated fatty acids: single C–C bonds vs. C=C double bonds; presence of double bonds introduces kinks, reducing packing and melting point.
    • Cis vs. trans unsaturation: natural fats are mostly cis; trans fats arise from hydrogenation and are associated with health risks.
    • Cellulose vs. starch/glycogen: α-D-glucose polymers (starch/glycogen) store energy; β-D-glucose polymers (cellulose) provide structural strength in plants and are not digestible by humans without specific enzymes.
    • DNA vs. RNA: sugar (deoxyribose vs ribose), bases (A, G, C; T in DNA; U in RNA), and structural differences (double helix vs single strand).
  • Ethical, philosophical, and practical implications
    • Understanding molecular structure-function relationships informs fields from medicine to agriculture and material science.
    • Knowledge of health-related aspects of fats (saturated vs. unsaturated vs. trans fats) emphasizes dietary guidance and public health considerations.
  • Connections to broader biology
    • The carbon-based basis of life links chemistry to biology: chemistry explains how macromolecules assemble, stabilize, and interact within cells and organisms.
    • The evolution of molecular domains and protein folding demonstrates how biology leverages chemistry to build complex, regulated systems.
  • Quick recall prompts
    • What makes carbon uniquely suited to support diverse biomolecules? (Answer: tetravalence and ability to form stable bonds with C, H, O, N, S, etc., including polar and nonpolar bonds.)
    • How do dehydration and hydrolysis reactions oppositely affect polymer length? (Dehydration extends polymers; hydrolysis shortens them.)
    • Name the four levels of protein structure and the key forces stabilizing them. (Primary, Secondary, Tertiary, Quaternary; hydrogen bonds, ionic/polar interactions, hydrophobic effect, van der Waals forces, disulfide bridges.)