MT

Biochemistry: Protein Structure, Nucleic Acids, and Energy

Primary structure (1°)

  • The speaker uses a poppy necklace analogy: beads of different colors represent different types of amino acids. The sequence shown is:
    • purple, pink, purple, green, green, purple, pink, green, yellow, yellow, pink, orange, purple, pink, yellow, orange, pink.
  • This sequence is referred to as the primary structure of a protein.
  • An ordinal/leveling system is mentioned for structure levels, using a degree symbol to denote order:
    • 1° (primary), 2° (secondary), 3° (tertiary), 4° (quaternary). In notation, this is often written as 1^\circ, 2^\circ, 3^\circ, 4^\circ.
  • The order of amino acids determines where hydrogen bonding will occur, which in turn determines the secondary structures that form.

Secondary structure (2°)

  • Secondary structures arise from hydrogen bonds forming between the backbone atoms (the amine and carboxyl groups) of the amino acids, not between the side chains (R groups).
  • Two major forms discussed:
    • Alpha helix: a right-handed helix.
    • Beta pleated sheet: the chain runs back and forth to create a sheet-like arrangement.
  • The little dots shown in the diagram (\"dot-dot-dot\" lines) represent hydrogen bonds between backbone atoms that stabilize these structures.
  • Important distinction: these hydrogen bonds are not bonds with the side chains themselves.

Tertiary structure (3°)

  • The overall three-dimensional folding of a single polypeptide chain, incorporating all the secondary structures (alpha helices and beta sheets) into a compact form.
  • Side chain interactions drive tertiary structure:
    • Ionic bonds can form between acidic and basic side chains (long-range interactions).
    • Disulfide bonds ((\mathrm{S!!S})) can form between cysteine residues, creating strong covalent links that help stabilize the folded protein.
    • Hydrophobic side chains tend to cluster away from water, while hydrophilic side chains tend to be on the external surface in contact with water.
  • Not every stretch of protein is folded into a compact globule; some regions may be straight, or contain bends/loops/spirals while still contributing to the final 3D shape.

Quaternary structure (4°)

  • Quaternary structure refers to the organization of more than one polypeptide chain (subunits) into a functional complex.
  • Example: Hemoglobin, which has two alpha chains and two beta chains (two slightly different polypeptides). Each chain has its own tertiary structure, but the protein's biological function depends on the quaternary assembly.
  • Definition: whenever you have multiple polypeptide chains interacting to form a functional protein, that arrangement is called the quaternary structure.

Protein folding and function: real-world example and analogy

  • Protein folding is driven by the sequence (primary structure) and interactions among side chains; the final 3D shape determines function.
  • If you alter the shape, you alter function (structure dictates function).

Denaturation and renaturation (effects of heat and chemicals)

  • Denaturation: changing the shape of a protein (unfolding or partial unfolding) such that it loses its natural function.
  • Example: Cooking an egg. Heat unfolds the globular proteins in the liquid, forming new hydrogen bonds and ionic interactions, creating a solid protein matrix. Upon cooling, the structure may not fully revert to its original form.
  • Denaturation can be partial (some unfolding) or complete (fully denatured). Function is often lost when the structure is altered.
  • Renaturation: under some conditions, denatured proteins can refold into their original shapes; in other cases (like hair perms), chemicals temporarily denature proteins to reshape them, after which the protein can renature into a different form.
  • Denaturation is not limited to heat; chemical denaturation (e.g., perms) can also alter structure.

Egg temperature example and biological implications

  • Dengue fever anecdote: high fever (103–104 °F) correlates with protein instability; high body temperatures can disrupt protein structure and function.
  • If body temperature regulation fails (hypothalamus dysfunction), overheating can lead to heat stroke and death.
  • Practical lesson: temperature affects protein stability and pathogen viability; optimal temperature is important for biological processes.

How the body processes proteins (digestion and reuse)

  • When you eat a protein, it is broken down into amino acids; amino acids themselves are not destroyed by digestion unless you burn them (extreme metabolism).
  • The body can reuse amino acids to build new proteins, but it cannot directly reuse whole proteins as a structure in the body.
  • Even if you eat cartilage (or bone), the components are broken down and rebuilt into new molecules (e.g., glucosamine, chondroitin sulfate) rather than directly substituting damaged tissue.
  • This underscores that digestion breaks proteins into amino acids, which are then reassembled as needed.

Nucleic acids: DNA, RNA, and ATP

  • Monomer: nucleotide.
  • Large molecules: DNA is among the largest in the body.
  • Each nucleotide has three components:
    • Sugar (deoxyribose in DNA; ribose in RNA),
    • Phosphate group,
    • Nitrogenous base.
  • Bases are polar due to NH groups, and can form hydrogen bonds.
  • DNA structure:
    • Double helix held together by hydrogen bonds between bases.
    • Base pairing rules (DNA): A\text{-}T \text{ (2 hydrogen bonds)}, \; G\text{-}C \text{ (3 hydrogen bonds)}.
    • A pairs with T via two hydrogen bonds; G pairs with C via three hydrogen bonds.
  • RNA structure:
    • Mostly single-stranded; can form local helices and folds.
    • Bases: A, C, G, U (Uracil replaces thymine).
    • Base pairing in RNA can be similar (A-U, G-C) but typically occurs within single strands or with RNA-DNA hybrids during transcription/translation.
  • Sugar differences:
    • DNA uses deoxyribose: the sugar lacks one oxygen atom compared to ribose.
    • RNA uses ribose.
  • DNA versus RNA locations and roles:
    • DNA is generally found in the nucleus; RNA is synthesized in the nucleus and then moves to the cytoplasm.
    • DNA stores genetic information; RNA (including messenger RNA) carries instructions to build proteins.
  • Key enzymes in DNA processing (mentioned):
    • Helicase: unwinds the DNA double helix,
    • Polymerase: synthesizes new DNA strands,
    • DNA ligase: seals gaps in the sugar-phosphate backbone.
  • Terminology note:
    • The suffix \"-ase\" denotes an enzyme (e.g., helicase, polymerase, ligase).
  • Messenger RNA (mRNA): a copy of a DNA gene that contains the instructions to build a protein; may form a simple helix or other shapes as it functions.

ATP, ADP, and cellular energy

  • ATP stands for adenosine triphosphate (ATP) and is the most common universal energy carrier in cells.
  • Structure: adenosine plus three phosphate groups ((\mathrm{P_i}) groups).
  • High-energy phosphate bonds: these phosphoanhydride bonds store energy that can be released to do work.
  • Examples of work powered by ATP:
    • Myosin-actin interaction to drive muscle contraction,
    • Na+/K+ ATPase pump that exchanges ions across membranes (3 Na+ out, 2 K+ in per ATP hydrolyzed).
  • Hydrolysis reaction (coupled to work):
    • General form: \mathrm{ATP} + \mathrm{H2O} \rightarrow \mathrm{ADP} + \mathrm{Pi} + \Delta G_{\text{rxn}}.
    • The energy released drives cellular processes.
  • ATP regeneration (recycling):
    • ADP + \text{P_i} (inorganic phosphate) can be recharged back to ATP using energy from metabolism.
    • This allows ATP to be reused repeatedly as an energy currency.
  • The cycle can be summarized as: \text{ADP} + \text{P_i} \xrightarrow{\text{energy from catabolism}} \text{ATP}, and ATP hydrolysis returns energy to power cellular work.
  • What can and cannot directly contribute to ATP production:
    • Electrolytes themselves are required for proper cellular processes but cannot by themselves generate ATP simply by ingestion.
    • Water and electrolytes support metabolic reactions; energy comes from breaking down nutrients (carbohydrates, fats, and proteins).
    • Example clarification from the session: drinking only water will not produce ATP directly; fats (lipids) or carbohydrates must be metabolized to provide energy.
  • Cholesterol and energy production:
    • You cannot directly burn cholesterol to produce energy in the same way as glucose or fatty acids; cholesterol is synthesized/metabolized in other pathways, but it is not a primary fuel source for ATP production.
  • Summary: ATP is regenerated through cellular metabolism using nutrients; ATP hydrolysis powers many processes, including muscle contraction and active transport.

Practical takeaways and review prompts

  • Denaturation vs renaturation: recognize factors that disrupt or restore protein structure (heat, chemicals).
  • The relationship between structure levels and function: primary sequence determines folding; higher-order structures enable biological activity.
  • Nucleic acid chemistry basics: sugar, phosphate backbone, and base pairing rules; differences between DNA and RNA; location and function in the cell.
  • Energy biology basics: ATP as the energy currency; hydrolysis drives work; regeneration cycles; role of enzymes and ion pumps.
  • Real-world example connections: egg cooking as a visual of denaturation; hemoglobin as a quaternary protein complex; dengue fever temperature sensitivity as a practical implication of protein stability.

Quick glossary (from the lecture)

  • Primary structure: the sequence of amino acids in a protein. 1^\circ
  • Secondary structure: local folded structures like alpha helices and beta sheets stabilized by backbone hydrogen bonds. 2^\circ
  • Tertiary structure: the overall 3D shape of a single polypeptide chain. 3^\circ
  • Quaternary structure: the arrangement of multiple polypeptide subunits in a protein. 4^\circ
  • Hydrogen bond: a weak bond between a hydrogen atom and an electronegative atom (often N or O) that helps stabilize structures.
  • Ionic bond: electrostatic attraction between oppositely charged side chains.
  • Disulfide bond: covalent bond between two cysteine residues (–S–S–).
  • Hydrophobic interaction: clustering of nonpolar side chains away from water.
  • Hydrophilic interaction: exposure of polar side chains to water.
  • Denaturation: unfolding of a protein, leading to loss of function.
  • Renaturation: restoration of the protein's functional structure under suitable conditions.
  • Nucleotide: monomer of nucleic acids (sugar + phosphate + base).
  • Nucleoside vs nucleotide: nucleoside is sugar + base; nucleotide includes phosphate groups.
  • Deoxyribose vs ribose: sugar in DNA is deoxyribose; RNA uses ribose.
  • Bases for DNA/RNA: DNA uses A, C, G, T; RNA uses A, C, G, U.
  • Base pairing rules: A-T\ (DNA) = 2\text{-H bonds},\ G-C = 3\text{-H bonds};\ A-U\ (RNA) = 2\text{-H bonds};\ G-C = 3\text{-H bonds}.