physiology 8/25

Nucleic Acids (DNA & RNA)

  • Nucleic acids build our DNA and RNA. DNA is the genetic makeup – the map or schematic for building all cells, tissues, and organs.
  • RNA copies DNA and helps implement the blueprint; RNA acts like the messages that travel to specific parts of the cell to guide production.
  • Conceptual metaphor used: DNA is the full blueprint; RNA is the distributed instructions sent to different areas (like glass or microchip instructions) to build specific parts.
  • Two main sugars in nucleic acids:
    • Deoxyribose (DNA side)
    • Ribose (RNA side)
  • Nucleotides consist of three parts: a sugar (ribose or deoxyribose), a nitrogenous base (purine or pyrimidine), and a phosphate group.
  • Purines: A and G. Pyrimidines: C, T, and U (RNA uses U instead of T).
  • DNA bases: A, T, C, G. RNA bases: A, U, C, G.
  • Base-pairing rules (stabilize the double helix and encode information):
    • In DNA, A pairs with T and G pairs with C: $A!:!T$, $G!:!C$.
    • In RNA, A pairs with U, and G pairs with C: $A!:!U$, $G!:!C$.
  • DNA structure: double helix with a sugar–phosphate backbone; the sequence of base pairs determines the genetic info.
  • RNA’s role: decodes DNA and helps determine amino acid sequences to form polypeptide chains (proteins).
  • The genetic code is stored in genes within DNA; RNA is used to translate that code into proteins.
  • A simplified view of the central dogma: DNA is transcribed into RNA, which is translated into proteins.

DNA Structure and Base Pairing Details

  • DNA is the genetic blueprint that stores information in a double-helix structure.
  • Complementary base pairing:
    • Adenine (A) pairs with Thymine (T) via two hydrogen bonds.
    • Guanine (G) pairs with Cytosine (C) via three hydrogen bonds.
  • The order of base pairs constitutes the genetic code that determines amino acid sequences in proteins.
  • The backbone of DNA is a phosphate-sugar chain; the bases project inward to pair with the opposite strand.

Nucleic Acids: Sugars, Bases, and Phosphates

  • Two sugars involved:
    • Deoxyribose in DNA (lacks one oxygen compared to ribose).
    • Ribose in RNA.
  • Nitrogenous bases are either purines or pyrimidines:
    • Purines: $A$, $G$.
    • Pyrimidines: $C$, $T$, $U$ (RNA uses $U$; DNA uses $T$).
  • Nucleotides link to form nucleic acids via a phosphate backbone.
  • RNA is used to decode DNA and send out instructions to cellular machinery to build proteins.

Proteins: Composition, Roles, and Examples

  • Proteins share elements with carbohydrates: carbon, hydrogen, oxygen; they also contain nitrogen (and sometimes sulfur) in their structure; phosphorous can appear in some contexts (e.g., phosphoproteins).
  • Protein architecture often includes a main body with tails or extensions; proteins support structure, contraction (muscles), transport (hemoglobin, lipoproteins), and storage.
  • Storage proteins: casein (milk), ferritin (stores iron in liver/spleen).
  • Hormones: regulate metabolism and nervous system (e.g., insulin regulates blood glucose; growth hormone regulates growth).
  • Enzymes: proteins that catalyze biochemical reactions, lowering activation energy.
    • Example: Sucrase catalyzes the hydrolysis of sucrose.
    • Hydrolysis means breaking a molecule with water; lysis denotes breaking apart; hydrolysis of sucrose yields glucose and fructose:
      C<em>12H</em>22O<em>11+H</em>2O→2 C<em>6H</em>12O6\text{C}<em>{12}\text{H}</em>{22}\text{O}<em>{11} + \text{H}</em>{2}\text{O} \rightarrow 2\ \text{C}<em>{6}\text{H}</em>{12}\text{O}_{6}
  • Immunoglobulins (antibodies) protect and stimulate immune responses.
  • Proteins are synthesized in cells but are not stored long-term; they are moved to where they are needed and used up.

Cell Organelles and Protein Synthesis: Where It All Happens

  • A typical cell contains:
    • Nucleus (genetic information; brain of the cell by analogy).
    • Cytoplasm (cytosol) where many processes occur.
    • Cell membrane with membranous organelles.
    • Mitochondria (energy production) – key in aerobic respiration.
    • Endoplasmic reticulum (ER): rough ER with ribosomes; smooth ER without ribosomes.
    • Golgi apparatus (modifies, packages, and ships proteins).
    • Lysosomes, peroxisomes (degradation and detoxification).
    • Lipid droplets (fat storage within cytoplasm).
    • Glycogen granules (stored glucose in liver/muscles).
    • Ribosomes (protein synthesis): free-floating or attached to rough ER.
  • Ribosomes: made of protein and RNA; two subunits (small and large).
    • Free ribosomes synthesize proteins used within the cytosol.
    • Ribosomes attached to rough ER synthesize proteins destined for secretion or membranes.
  • Central dogma in this context: DNA transcribed into RNA by RNA polymerase; RNA translated at ribosomes into proteins.
  • Transcription details:
    • Initiation at promoter regions; RNA polymerase binds and unzips DNA locally.
    • Primary RNA transcript is formed.
    • RNA splicing removes introns and joins exons to form mature mRNA.
    • Mature mRNA exits the nucleus to the cytoplasm.
  • Translation details:
    • mRNA binds to the ribosome (small subunit first).
    • Transfer RNAs (tRNAs) bring specific amino acids to the ribosome.
    • Amino acids are linked by peptide bonds to form a growing polypeptide chain.
    • Translation proceeds until a termination (stop) codon is reached.
  • Directionality and localization:
    • Some proteins are synthesized on ribosomes in the cytosol; others on ribosomes in the rough ER and are transported via the Golgi to their destinations (outside the cell or membranes).
  • A metaphor used: Apple’s blueprint analogy – different factory groups translate parts of the blueprint into external components; tRNAs supply materials to the ribosome factory; the completed product is sent to its destination.
  • Important enzymes in the context of digestion and metabolism:
    • Trypsin catalyzes hydrolysis of proteins in the digestive system.
    • Sucrase catalyzes hydrolysis of sucrose.

Protein Structure: Four Levels and Examples

  • Primary structure: linear sequence of amino acids (20 standard amino acids).
  • Secondary structure: local folding stabilized by hydrogen bonds; two main forms:
    • Alpha helices: coiled structures similar to a spiral;
    • Beta pleated sheets: sheet-like folds.
  • Tertiary structure: entire 3D folding of a single polypeptide, producing its overall shape.
  • Quaternary structure: assembly of multiple polypeptide chains into a functional protein; e.g., hemoglobin (Hb) has four subunits and a quaternary structure.
  • Collagen is a fibrous protein with a quaternary-like assembly (multiple alpha helices braided for strength).
  • Hemoglobin specifics: a four-subunit protein that carries oxygen in the blood; its quaternary structure is essential for function.
  • Sickle cell anemia: a mutation in the hemoglobin protein that causes misfolding and a sickling shape of red blood cells, especially under low oxygen; higher risk at high altitude, linking structure to disease.
  • CRISPR: gene-editing technology aimed at correcting genetic causes of diseases like sickle cell anemia by modifying DNA/RNA regions.
  • mRNA vaccines (e.g., COVID-19): rely on mRNA to instruct cells to make a protein that elicits an immune response; the concept depends on understanding RNA and protein synthesis.

Protein–Ligand Interactions and Membranes

  • Proteins interact with ligands via binding sites. A ligand is any molecule or ion that binds to a protein.
  • Binding can be non-covalent and reversible and is driven by:
    • Electrostatic attraction and hydrophobic interactions.
  • Binding sites can have multiple sites (one protein may have several binding sites).
  • Induced-fit vs lock-and-key models describe how binding changes protein shape to enable function.
  • Ligand binding can activate or inhibit protein function, depending on the context.
  • Receptors and signaling: extracellular signals bind to receptors, triggering transcription factors that move to the nucleus to promote gene transcription.
  • Why receptor signaling can be necessary: some ligands are hydrophilic and cannot cross the lipid bilayer; others are lipophilic and may cross the membrane directly.
  • The cell membrane basics:
    • Phospholipid bilayer: hydrophilic heads (phosphate groups) face outward; hydrophobic tails face inward.
    • Membrane proteins can span the bilayer or be anchored to one side, enabling interaction with the cell's exterior and interior.
  • Induced fit and docking at the membrane influence protein function and localization.

The Cell Membrane, Lipids, and Transport Concepts

  • Phospholipid bilayer composition: hydrophilic heads and hydrophobic tails create a selective barrier.
  • Membrane proteins provide pathways and functions (channels, receptors, transporters).
  • The role of receptor signaling in gene expression:
    • Extracellular signal binds receptor → activates transcription factors → translocate to nucleus → promote transcription.
  • Lipid-soluble (nonpolar) molecules can sometimes cross membranes directly; others require receptors or