Structure and Function of Large Biological Molecules

General Biochemistry Concepts

• Macromolecules are large polymers built from repeating smaller units called monomers.

• Polymers include carbohydrates, proteins, and nucleic acids.

• Lipids are a class of large biological molecules but are not true polymers.

• Dehydration reaction: Monomers bond together by losing a water molecule to form a polymer.

• Hydrolysis: Polymers are broken down into monomers by adding a water molecule.

• Enzymes are specialized macromolecules (proteins) that speed up these chemical reactions.

Carbohydrates: Fuel and Building Material

• Monosaccharides (simple sugars) are the simplest carbohydrates (e.g., glucose, fructose).

  • Molecular formula typically $C<em>nH</em>{2n}O<em>n$ (multiple of $CH</em>2O$).

  • Classified by carbonyl group location (aldose/ketose) and carbon number (trioses, pentoses, hexoses).

  • Form rings in aqueous solutions; serve as cell fuel and building material.

• Disaccharides are formed by joining two monosaccharides via a glycosidic linkage (a covalent bond) in a dehydration reaction (e.g., maltose, sucrose).

• Polysaccharides are polymers of many monosaccharide (sugar) building blocks.

  • Architecture and function depend on sugar monomers and glycosidic linkage positions.

  • Storage Polysaccharides:

    • Starch: Plant storage polysaccharide made of $\alpha$ glucose monomers (amylose is simplest, amylopectin is branched).

    • Glycogen: Animal storage polysaccharide (liver, muscle cells), extensively branched.

  • Structural Polysaccharides:

    • Cellulose: Major component of plant cell walls, polymer of $\beta$ glucose monomers.

      • $\alpha$ and $\beta$ glucose ring forms differ in hydroxyl group position on carbon-1.

      • Cellulose molecules are straight and unbranched, forming microfibrils enhanced by hydrogen bonds between parallel chains.

      • Humans cannot digest $\beta$ linkages; it's “insoluble fiber.”

    • Chitin: Found in arthropod exoskeletons and fungal cell walls for structural support.

Lipids: Diverse Hydrophobic Molecules

• Lipids are hydrophobic (mix poorly with water) due to mostly hydrocarbon regions.

• Not true polymers; major types: fats, phospholipids, steroids.

• Fats (Triacylglycerols):

  • Composed of two smaller molecules: glycerol (three-carbon alcohol) and fatty acids (carboxyl group + long carbon skeleton).

  • Three fatty acids join to glycerol via ester linkages (dehydration reaction).

  • Saturated fatty acids: Maximum hydrogen atoms, no double bonds, solid at room temperature (e.g., animal fats).

  • Unsaturated fatty acids: One or more double bonds (cis or trans), liquid at room temperature (oils, plant/fish fats).

    • Trans fats (hydrogenated oils with trans double bonds) and high saturated fat intake contribute to cardiovascular disease.

  • Function: Primary energy storage; insulate and cushion organs in adipose cells.

• Phospholipids:

  • Two fatty acids and a phosphate group attached to glycerol.

  • Hydrophilic head (phosphate group) and hydrophobic tails (fatty acids).

  • Form bilayers in water, crucial for cell membranes (boundary between cell and environment).

• Steroids:

  • Characterized by a carbon skeleton of four fused rings.

  • Cholesterol: Component of animal cell membranes and precursor for other steroids; high levels linked to cardiovascular disease.

Proteins: Diversity of Structure and Function

• Over 50% of cell dry mass, performing diverse functions:

  • Enzymatic: Catalyze reactions.

  • Defensive: Antibodies.

  • Storage: Amino acid reserves (e.g., casein, ovalbumin).

  • Transport: Transport substances (e.g., hemoglobin, membrane channels).

  • Hormonal: Coordinate activities (e.g., insulin).

  • Receptor: Respond to chemical stimuli.

  • Contractile/Motor: Movement (e.g., actin, myosin).

  • Structural: Support (e.g., keratin, collagen).

• Monomers: Amino acids (20 types).

  • Organic molecules with amino ($NH_2$) and carboxyl ($COOH$) groups.

  • Distinguished by their unique side chains (R groups), which dictate properties (nonpolar, polar, charged).

• Polypeptides: Unbranched polymers of amino acids linked by peptide bonds (covalent bonds formed via dehydration).

  • Each has a unique linear sequence from N-terminus (amino end) to C-terminus (carboxyl end).

• Protein Structure & Function:

  • A functional protein consists of one or more polypeptides precisely folded into a unique 3D shape.

  • Specific structure determines recognition and binding capabilities.

  • Four levels of protein structure:

    • Primary structure: Unique linear sequence of amino acids (determined by genes).

    • Secondary structure: Coils ($\alpha$ helix) and folds ($\beta$ pleated sheet) in the polypeptide backbone, formed by hydrogen bonds between repeating backbone atoms.

    • Tertiary structure: Overall 3D shape of a single polypeptide, determined by interactions among R groups (hydrogen bonds, ionic bonds, hydrophobic interactions, van der Waals forces, disulfide bridges).

    • Quaternary structure: Results from the association of two or more polypeptide chains (subunits) into one functional macromolecule (e.g., collagen, hemoglobin).

  • Sickle-cell disease: Caused by a single amino acid substitution in hemoglobin, altering protein structure and function.

  • Denaturation: Loss of a protein’s native structure (unraveling) due to adverse physical/chemical conditions (pH, salt, temperature), rendering it biologically inactive.

  • Protein folding can be difficult to predict; misfolded proteins are linked to diseases (Alzheimer’s, Parkinson’s).

  • X-ray crystallography, NMR spectroscopy, and bioinformatics are used to determine protein structure.

Nucleic Acids: Hereditary Information

• Store, transmit, and help express hereditary information.

• Types: Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA).

• Central Dogma: DNA directs its own replication, controls mRNA synthesis, and through mRNA, dictates protein synthesis (gene expression).

  • Flow of genetic info: $DNA \to RNA \to protein$

• Monomers: Nucleotides.

  • Nucleoside: Nitrogenous base + pentose sugar.

  • Nucleotide: Nitrogenous base + pentose sugar + one or more phosphate groups.

  • Nitrogenous bases:

    • Pyrimidines: Single six-membered ring (Cytosine, Thymine (in DNA), Uracil (in RNA)).

    • Purines: Six-membered ring fused to a five-membered ring (Adenine, Guanine).

  • Pentose sugar:

    • Deoxyribose in DNA (lacks an oxygen at the 2' carbon).

    • Ribose in RNA.

• Polynucleotides: Nucleotides linked by phosphodiester linkages (a phosphate group linking sugars of two nucleotides), forming a sugar-phosphate backbone with nitrogenous bases as appendages.

• DNA Structure:

  • Two polynucleotides spiraling as a double helix.

  • Backbones run antiparallel (5'$\to$3' and 3'$\to$5').

  • Complementary base pairing: A always pairs with T (two hydrogen bonds); G always pairs with C (three hydrogen bonds).

• RNA Structure: Single-stranded; uracil (U) replaces thymine (T), so A pairs with U.

• Molecular Biology Techniques:

  • Genomics: Analyzing large sets of genes or comparing whole genomes.

  • Proteomics: Analyzing large sets of proteins and their sequences.

  • These fields use bioinformatics (computational tools) to process vast amounts of data.

  • Gene and protein sequences provide insights into evolutionary relationships between organisms.