chapter 4 deep notes

Cell: Structure and Function

• Cell is the basic living unit; it is the structural and functional unit of an organism
• Regulates organismal activity via compartments and controlled inflow/outflow of materials
• Genes regulate cellular functions
• Cytology: cyto- meaning cell; -logy meaning study

Generalized Cell Structures

• Plasma membrane: the cell boundary that controls traffic and determines solubility and function
• Nucleus: dark-staining, central organelle
• Cytoplasm: cytosol (the “jelly”) + organelles (cell organs)

Plasma Membrane

• Fluid mosaic model: plasma membrane is a fluid phospholipid bilayer with embedded proteins
• Key components:
  • Phospholipid bilayer with amphipathic phospholipids (polar heads, nonpolar tails)
  • Cholesterol
  • Glycolipids and Glycoproteins (carbohydrate portions on the extracellular surface)
  • Integral (transmembrane) proteins and peripheral proteins (attached to the surface)
• Cytoskeletal interactions: filaments of the cytoskeleton associate with the membrane
• Interstitial fluid resides outside the cell; cytosol is inside

Peripheral Membrane Proteins vs. Integral Membrane Proteins

• Peripheral proteins: attached to the outside of the plasma membrane
• Integral proteins: embedded in the membrane; not all cross completely through the bilayer

Functions of Membrane Proteins

• Membrane proteins vary between cell types; different proteins confer specific functions
• Major functional categories:
  • Transport proteins: channels/pores; carriers/pumps (transporters)
  • Receptors
  • Enzymes
  • Linkers/Anchoring sites
  • Cell-adhesion proteins
  • Cell-identity markers

Membrane Fluidity

• Membranes are fluid and dynamic; fluidity is temperature-dependent
• Self-sealing if punctured and freely moveable
• Interactions are hydrophobic/philic; cholesterol decreases membrane fluidity when inserted

Selectively Permeable Membrane

• Impermeable to macromolecules and tiny charged molecules
• Permeable to small, uncharged molecules and water via aquaporins

Gradients Across the Plasma Membrane

• Concentration gradients; ions have electrochemical gradients
• Gradients store potential energy
• Substances tend to move down their concentration gradient (high → low)

Principles of Diffusion

• Random mixing results from kinetic energy (heat)
• Rate of diffusion varies with:
  • Concentration gradient
  • Temperature
  • Surface area
  • Size of molecule
  • Diffusion distance
• Dynamic equilibrium: a = b

Osmosis

• Diffusion of water across a selectively permeable membrane
• Aquaporins facilitate water movement
• Aqua = water; porin = pore

Effect of Membrane Permeability on Diffusion and Osmosis

• Diffusion of solute (left to right): depends on solute permeability of the membrane
• If membrane is permeable to solute and water, water movement and solute movement depend on osmolarities
• If membrane is impermeable to solute but permeable to water, osmotic flow can change volume without solute movement
• Example diagrams illustrate water vs. solute movement and volume changes when osmolarity differs

Osmosis in Cells: Tonicity

• Solutions contain solute and solvent (water)
• Tonicity categories:
  • Isotonic: same osmolarity as cell interior (e.g., 0.9% NaCl in humans)
  • Hypotonic: lower external osmolarity; can cause hemolysis
  • Hypertonic: higher external osmolarity; can cause crenation

Facilitated Diffusion Through Membrane Channels

• Diffusion through membrane channels is slower than lipid bilayer diffusion
• Important for nutrient absorption and waste excretion
• Channels are specific and may be open or gated
• Suitable for nonpolar? Actually channels typically permit ions or polar molecules that cannot readily cross the lipid bilayer

Facilitated Diffusion Using a Carrier Protein

• Substances pass via carrier proteins down their concentration gradients
• Carrier proteins undergo conformational changes to move the solute
• No direct energy input required
• Rate depends on the gradient steepness and the number of transporter proteins

Primary Active Transport

• Moves polar/charged substances against their concentration gradient; requires energy
• Carrier molecule uses energy (usually ATP)
• Example: Na+/K+-ATPase pump
  • Maintains osmotic balance across the membrane
  • ATP is the cellular energy source
• Na+/K+ Pump steps (illustrative sequence):
  1) Na+ binding
  2) ATP is split; phosphate (P_i) binds to the pump
  3) Pump undergoes conformational change; Na+ is pushed out
  4) K+ binds to the pump
  5) Phosphate is released; pump returns to original conformation, K+ is pushed in
  6) Pump ready to bind Na+ again
• Overall reaction involves ATP hydrolysis: ext{ATP}
  ightarrow ext{ADP} + ext{P}_i

Secondary Active Transport

• Uses energy stored in ion gradients (usually Na+) to move other substances against their gradient
• Na+/K+ pump maintains steep Na+ gradient across the plasma membrane
• Types: Na+ antiporters and Na+ symporters
• Gradient-driven transport is a form of indirect energy use

Vesicular Transport - Exocytosis

• Exocytosis exports cellular contents out of the cell
• Vesicles form inside the cell and fuse with the plasma membrane to release contents

Vesicular Transport - Endocytosis

• Phagocytosis (cell eating):
  • Pseudopods surround the particle to form a phagosome
  • Lysosome fuses to form a phagolysosome and digestion occurs
• Pinocytosis (cell drinking):
  • No receptor proteins or pseudopods; vesicles form to bring in extracellular fluid
• Receptor-mediated Endocytosis: selective uptake via receptors
  • Clinically relevant examples: HIV entry mechanisms; familial hypercholesterolemia

Vesicular Transport - Transcytosis

• Endocytosis on one side → vesicle crosses the cell → exocytosis on the opposite side
• Examples: molecules including some antibodies cross the placenta; substances traverse between blood and interstitial fluid

Blood–Brain Barrier

• Specialized barrier that sequesters chemically sensitive areas like the brain and fetus
• Limits passage of many substances to protect neural tissue

Passive Membrane Transport – Review

• Simple diffusion: energy source is concentration gradient; example: oxygen diffusion across membranes
• Facilitated diffusion: requires a gradient; glucose uptake via transporters
• Osmosis: water diffusion along concentration gradient

Active Membrane Transport – Review

• Includes primary and secondary active transport (transporters, symporters, antiporters)
• Exocytosis, endocytosis, receptor-mediated endocytosis, transcytosis
• Energy source: ATP or concentration gradient
• Examples: glucose uptake via glucose transporters; H+ antiporters; neurotransmitter release via exocytosis; WBC phagocytosis & pinocytosis; antibody transfer via transcytosis

Clinical View: Receptor-Mediated Endocytosis and Vaccines

• mRNA vaccines use lipid-coating (lipid nanoparticles) to enter cells
• Entry mechanism is similar to endocytosis: lipid coat is recognized and internalized by the cell
• Cells can communicate using similar vesicular uptake and signaling mechanisms

Endosome, Lipid Nanoparticle, and mRNA Release

• Endosome forms after lipid-coated mRNA enters; pH decreases within endosome to trigger mRNA release
• Lipid nanoparticle carries mRNA into the cytoplasm where translation occurs

Cell Communication

• Direct contact: immune cells distinguish self from non-self; sperm-egg fusion; epidermal regrowth
• Ligand–receptor signaling: signaling molecules bind receptors to elicit cellular responses across systems

Ligand-Receptor Signaling

• Channel-linked receptors (ion channels): open in response to ligand binding; ions move through channel; initiates electrical signals in muscle and nerve cells
• Enzymatic receptors: protein kinases phosphorylate target proteins to alter enzymatic activity
• G protein-coupled receptors (GPCRs): activate second messengers that amplify receptor signaling; link receptor activation to downstream effectors (ions or enzymes)
• Mechanism sketch (conceptual):
  • Ligand binds receptor → conformational change → G protein activation (for GPCRs) or kinase activation (for enzymatic receptors) or direct ion channel modulation
  • Second messengers propagate the signal, leading to a cellular response

Cytoplasm, Nucleus, and Protoplasm

• Cytoplasm: all contents of the cell excluding the nucleus; includes cytosol and organelles
• Cytosol: liquid component; site of many chemical reactions (e.g., ATP production, synthesis of building blocks)
• Protoplasm: cytoplasm comprising cytosol, organelles, inclusions

Cytosol

• Contains large and small organic/inorganic molecules, inclusions, and organelles
• Site of important chemical reactions (e.g., ATP production, biosynthesis)

Cell Organelles

• Organelles: membranous and non-membranous compartments with specific functions
• Distinguish between membranous and non-m membranous components

Cytoskeleton

• Network of protein filaments providing structural support and organization
• Three major types: microfilaments (actin), intermediate filaments, microtubules
• Dynamic; supports shape, movement, and intracellular transport

Centrosome and Centriole

• Centrosome near the nucleus; centriole is a component within the centrosome
• Functions include organizing the mitotic spindle and aiding chromosome separation during division

Cilia and Flagella

• Cilia: many short, hair-like projections; move substances across the cell surface
• Flagellum: a long, singular projection; enables cell locomotion (e.g., sperm)

Ribosomes

• Complexes of RNA and protein; two subunits; types:
  • Free ribosomes (synthesize proteins for use inside the cell)
  • Membrane-bound ribosomes (RER) (synthesize proteins destined for secretion or lysosomes or plasma membrane)
• Sites of protein synthesis

Endoplasmic Reticulum

• Network of folded membranes
• Rough ER: ribosomes attached; synthesizes, processes, and packages proteins for export or insertion into membranes
• Smooth ER: lacks ribosomes; synthesizes lipids (phospholipids, steroids), metabolizes carbohydrates, detoxifies drugs/alcohol/poisons; forms vesicles and peroxisomes

Golgi Complex

• Series of elongated, flattened sacs (cisternae)
• Modifies, sorts, and packages proteins produced by the rough ER
• Two faces:
  • Cis face (receives vesicles from ER)
  • Trans face (ships modified proteins in secretory vesicles or lysosomes)
• Involves vesicle traffic between ER and Golgi and from Golgi to plasma membrane or lysosomes

Lysosomes

• Membranous vesicles formed from Golgi; contain digestive enzymes; acidic interior (pH ≈ 5.0)
• Functions: digest foreign substances, autophagy (self-eating)
• Clinical: Tay–Sachs disease (lysosomal storage disorder); Listeria monocytogenes can evade lysosomal enzymes

Peroxisomes

• Smaller than lysosomes; contain oxidases and catalases
• Functions: break down fatty acids, detoxify harmful substances; use oxygen to oxidize/destroy molecules

Proteasomes

• Tiny barrel-shaped protein complexes; degrade damaged or unneeded proteins; proteolysis
• Clinical relevance: link to neurodegenerative diseases like Alzheimer’s and Parkinson’s due to proteostasis failure

Mitochondria

• Double-membrane with matrix and cristae
• Functions: ATP synthesis via aerobic respiration; can self-replicate; maternal inheritance patterns

Nucleus

• Large organelle with double-membrane nuclear envelope; contains genetic material
• Nuclear pores permit exchange with cytoplasm
• Nucleolus: site of ribosomal protein synthesis; ribosome assembly

Nucleus and Genetic Material

• Dividing cells contain chromosomes (DNA tightly packed); non-dividing cells contain chromatin (loosely packed DNA)
• Humans have 46 chromosomes; genes are located on them

Protein Synthesis and Central Dogma

• Most cellular proteins arise from transcription and translation processes
• Types of proteins: structural, secreted antibodies/hormones/neurotransmitters, receptors, enzymes, contractile elements, transporters
• Central Dogma: DNA -> RNA -> Protein
• DNA replication occurs for cell division; transcription and translation produce proteins
• Central flow of genetic information: DNA transcribed to RNA, RNA translated to protein

Types of RNA

• mRNA: Messenger RNA; encodes the protein sequence
• rRNA: Ribosomal RNA; part of ribosome structure, translates mRNA into protein
• tRNA: Transfer RNA; brings amino acids and matches codons with anticodons

Nucleotide Pairing and Bases

• DNA base pairing: $T ext{-} A, ext{ and } C ext{-} G$
• RNA base pairing: $A ext{-} U, ext{ and } C ext{-} G$
• Nucleotide pairing detail: DNA uses thymine (T) and RNA uses uracil (U)

Summary of Transcription & Translation

• Transcription (nucleus): DNA → Pre-mRNA → mature mRNA; processing includes introns/exons
• Translation (cytoplasm): mRNA → tRNA with anticodons → amino acid sequence → polypeptide
• Key components: ribosome, mRNA, tRNA
• Mature mRNA exits nucleus to be translated

mRNA & Transcription Details

• Carries the genetic message from DNA to ribosome
• Transcription involves promoters, terminators, RNA polymerase, and RNA processing (introns/exons, snRNPs)
• Pre-mRNA is processed to mature mRNA before leaving the nucleus

Ribosomal RNA Structure

• Ribosomes have two subunits (large and small)
• The large subunit contains E, P, and A sites; the small subunit holds the mRNA

Translation Overview

• Process of reading mRNA and assembling amino acids into a polypeptide
• Involves codons on mRNA, anticodons on tRNA, and ribosomal sites

Cell Division and Genetic Replication

• Normal cell division includes mitosis (somatic) and meiosis (gametes)
• Interphase precedes division: Growth and DNA replication
• Interphase stages:
  • G1: cell growth and organelle replication
  • S: DNA replication
  • G2: cytoplasmic growth
  • G0: some cells exit the cycle
• S phase details: DNA unwinding, replication by DNA polymerase, leading and lagging strands, sister chromatids
• Mitosis phases:
  • Prophase: chromatin condenses; nucleolus and nuclear envelope disappear; spindle forms
  • Metaphase: chromosomes align at the metaphase plate
  • Anaphase: sister chromatids separate and move to opposite poles
  • Telophase: chromosomes de-condense; nuclear envelope reforms
• Cytokinesis: division of cytoplasm and organelles; cleavage furrow forms; results in two daughter cells

Overview: Cell Division Stages (Summary Diagram Concepts)

• Interphase: DNA replication and cellular growth
• Prophase: chromosomes condense; spindle forms
• Metaphase: chromosomes align at the center
• Anaphase: chromatids separate to opposite ends
• Telophase: nuclei reform; chromosomes de-condense
• Cytokinesis: cytoplasm divides; two daughter cells form

Control of Cell Destiny

• Cell fate decisions: remain alive/functioning, grow/divide, or die (apoptosis)
• Homeostasis maintains balance between cell growth and cell death
• Regulatory molecules:
  • Cyclins rise during interphase and trigger mitosis
  • Apoptosis can be triggered by signals; necrosis is cell death due to injury or infection

p53 Gene – Tumor Suppressor

• p53 regulates apoptosis during the G1/S checkpoint
• Normal p53 promotes death of damaged cells
• Mutant p53 allows damaged cells to proliferate
• High proportion of human cancers linked to p53 mutations
• Elephant example: multiple copies of p53 gene contribute to cancer resistance (20 copies observed)

Cancer: Uncontrolled Cell Division

• Hyperplasia: increased cell divisions
  • Benign tumors do not metastasize
  • Malignant tumors metastasize via detachment and spread through blood/lymphatics
• Carcinogens drive carcinogenesis (multistep process with multiple mutations)

Apoptosis

• Programmed cell death; a normal developmental process
• Steps:
  1) Death receptor binds signal
  2) Enzymes dismantle cell structures
  3) Phagocytes remove cell debris
• Examples: removal of webbing in chick embryos

Necrosis

• Pathological cell death due to hypoxia or tissue damage

Aging

• Aging reflects reduced ability to adapt to environmental changes
• Theories exist; signs include wrinkled skin, stiff joints, hardened arteries