Download Biology Passage 2 - HCC Learning Web

Human Cell Biology
1. Organelles
a. Overview
b. The Secretory Pathway
2. Plasma Membrane
a. Membrane Structure
b. Diffusion and Osmosis
c. Transport Mechanisms
d. Resting Membrane Potential
3. Other Cellular Structural Elements
a. Cell Surface Receptors
b. Internal and External Structural Proteins
c. Cell Junctions
4. Cell Cycle and Mitosis
a. Cell Cycle
b. Mitosis and Karyotype Analysis
Organelles
A. Overview (number of membranes surrounding indicated in parentheses)
1. Nucleus (2)
a. Contains and protects DNA genome
b. Site of transcription
2. Mitochondria (2)
a. ATP production via Krebs cycle and Oxidative Phosphorylation
b. Has its own ds circular DNA; maternally inherited
c. endosymbiotic theory of evolution
3. Ribosomes (0)
a. Synthesis of cytosolic proteins
4. RER (1 – RER membrane contiguous with outer nuclear membrane)
a. Synthesis of secretory, membrane bound or organelle proteins
b. Rough: Ribosomes dot the reticulum
5. SER (1)
a. detoxification & glycogen breakdown – liver
c. steroid synthesis – gonads
6. Golgi (1)
a. further protein modification
b. sorts and secretes proteins out of a cell; constitutive or regulated secretion
7. Lysosomes (1)
a. contain acid hydrolase; phagocytosis and digestion
8. Peroxisomes (1)
a. contain peroxide; breakdown lipids and toxins
B. Secretory Pathway
1. Nucleus: mRNA is transcribed from DNA
2. mRNA is exported from the nucleus  cytoplasm
a. exit nucleus through nuclear pores
3. translation of mRNA to protein commences
a. NO N-terminal signal sequence (NSS) on the growing polypeptide; cytoplasmic
1. localization signal: sequence on polypeptide specifying organelle target
2. non-secretory targeting for nucleus, mitochondria or peroxisome
b. YES N-terminal Signal Sequence on the growing polypeptide; targeted to RER
1. Translation pauses; due to hydrophobic sequence and polypeptide folding
2. NSS binds to Signal Recognition Particle (SRP)
3. Complex relocates to the RER surface and binds
4. Hydrophobic NSS polypeptide resides are embedded into RER membrane
5. Translation proceeds, pushing growing polypeptide into the RER
6. When completed, signal peptidase removes NSS
7. Protein is packaged as a vesicle; exported to the Golgi
8. Golgi modifies the protein and secretes it as a vesicle
a. targeting signal: sequence on polypeptide specifying organelle target
1. secretory targeting for Golgi, RER, SER or lysosome
4. Vesicle transport mechanisms
a. Secreted Proteins:
package inside vesicle & exported through the membrane
b. Transmembrane Proteins:
part of vesicle & incorporated into target (organelle) membrane
Plasma Membrane
A. Membrane Structure
1. Function: separate environments [cell to exterior milieu]
2. Lipid Bilayer
a. composition
1. charged phospholipids (mostly)
2. less charged glycolipids (phospholipids with carbohydrate heads)
3. hydrophobic cholesterol (mostly inside the bilayer)
b. fluidity/rigidity
1. fluidity increased: unsaturated fatty acid chain tails, cholesterol
2. rigidity increased: saturated fatty acid chain tails
3. Proteins
a. functional types
1. cell surface receptors
2. channel transport proteins
3. cell to cell interacting proteins
b. structural types
1. integral
a. embedded, one side of bilayer
b. held by hydrophobic interaction with hydrophobic amino acids
2. peripheral
a. external, one side of bilayer
b. held by hydrogen bonds with hydrophilic amino acids
3. transmembrane
a. special integral, throughout bilayer
b. held by hydrophobic interaction with hydrophobic amino acids
4. Fluid Mosaic Model
a. membrane is dynamic: proteins and lipids are free to move
b. lateral movement (2D): heads – hydrophilic; tails – hydrophobic
c. plasma membrane has 2 sides
d. cytoskeletal proteins anchor the membrane – provide framework
B. Diffusion and Osmosis
Osmosis is a more biologically relevant concept than diffusion. Cell plasma
membranes are very particular to the flux of ions through transmembrane proteins,
whereas water freely diffuses through the lipid bilayer. Thus, a solution (solvent) can
be considered hyper-tonic (more solute), hypo-tonic (less solute) or isotonic (same
concentration) to the cell it surrounds. In addition, the flux of solvent in an effort to
achieve equilibrium of solute concentration on both sides of the membrane generates
an osmotic pressure.
C. Transport Mechanisms
1. Passive Transport
a. no energy input (Diffusion)
b. down concentration gradient
c. 2 types
1. Simple Diffusion
a. no transport proteins involved
b. not very common mechanism in cell biology
(mostly large molecules that are hydrophilic in character)
c. example: steroids (hydrophobic and small)
2. Facilitated Diffusion
a. 2 types of transport proteins involved
1. Channel Proteins
a. selective tunnels
b. ‘gated’ process; stimuli opens (voltage or ligand)
neurons are a great example of a gated process
2. Carrier Proteins
a. bind molecule; causes conformational change
b. transport is facilitated
1. uniport: 1 molecule / 1 direction
2. symport: 2 molecules / same direction
3. antiport: 2 molecules / opposite directions
d. Kinetics of Passive Transport
saturation kinetics is exhibited by facilitated diffusion
2. Active Transport
a. requires energy
b. against concentration gradient
c. 2 types
1. Primary Active Transport
a. couple transport to ATP hydrolysis – direct
2. Secondary Active Transport
a. couple transport to a secondary process - indirect
1. primary active transport mechanism sets up electrochemical gradient
2. potential energy of electrochemical gradient drives transport
d. flow of transport is reversible [into cell or out of cell]
D. Resting Membrane Potential (RMP)
1. maintained by the Sodium/Potassium ATPase transporter protein
a. [sodium] high outside cell; [potassium] high inside cell
b. ATP hydrolysis coupled to transport of these ions
2. generates a specific electrochemical potential (RMP) across the membrane
a. RMP helps drive Secondary Active Transport mechanisms
due to charge and concentration differences across the membrane
Other Cellular Structural Elements
A. Cell Surface Receptors
1. integral membrane proteins facilitating internal cell signaling – signal transduction
3. 3 types
a. Ligand-gated Ion Channels
1. ligand binding changes protein conformation (closed  open)
2. influx of ions acts as intracellular signal
b. Catalytic Receptors (direct transmission)
1. ligand binding changes protein conformation (closed  open)
2. activates enzyme (i.e. kinase) on cytoplasmic face of protein
3. directly triggers intracellular signal
c. G-protein Linked Receptors (indirect transmission)
1. ligand binding changes protein conformation (closed  open)
2. G-protein releases GDP (Gi – ) and binds GTP (Gs – )
a. Gs activates Adenylyl Cyclase; cAMP second messenger is produced
b. Gs activates phospholipase C; [Ca+2] second messenger is produced
3. Amplified Response through signal transduction cascade
B. Internal (Cytoskeleton) and External Structural Proteins
1. Microtubules
a. Structurally: hollow rods
b. Functionally: transport stuff (molecular railroads)
c. Construction
1. alpha-tubulin + beta-tubulin forms dimer
2. dimers form sheet; sheet rolls into tube (non-covalent bonding)
3. extend from Microtubule Organizing Center which is located at nucleus
a. Centrioles
1. special microtubule structure located within the MTOC
2. 9 Microtubule triplets form a ring
3. 2 rings make paired couple at a 90o angle to each other
4. duplicate and function during cell division
4. Flagella/Cilia
a. Cilia: small hairs on cell surface (mucociliary)
b. Flagellum: tail wiggles due to (9+2 arranged microtubule)-dynein ‘snap’
2. Microfilaments
a. Function: gross cell movement (pinching)
b. Construction: 2 Actin chains form wrapped polymers
3. Intermediate filaments
a. Construction: many polypeptides compose it
b. Function: cell structure (framework)
C. Cell Junctions
1. Tight Junctions
a. form tight seal between/around cells; blocks flow of molecules inbetween cells
b. apical vs. basolateral sides of a cell; orders flow through (i.e. intestinal cells)
2. Gap Junctions
a. pore like connections between cells
b. solute exchange/cytoplasmic mixing (i.e. heart muscle cells)
3. Adhering Junctions
a. hold cells together
b. keratin fibers span both membranes; Intermediate Filaments anchor inside
Cell Cycle and Mitosis
A. Cell Cycle
1. Phases (interphase through mitosis)
a. G1 – prepare the cell for DNA synthesis
b. S – duplicate genome (DNA)
c. G2 – prepare for cell division
d. M – partition cell components; evenly divide cell (cytokinesis)
2. Terminally differentiated (specialized) cells stopped in special G1 state called G0
B. Mitosis (M phase)
1. Prophase
a. chromosomes are fully condensed
b. sister chromatids attach at centromere
c. nucleolus around chromosomes disappears
d. centrioles move apart and asters form (microtubule radiations from centriole)
2. Metaphase
a. plate forms; sister chromatids line up (can do karyotype now)
b. asters are polarized [on opposite ends of the cell]
3. Anaphase
a. sister chromatids are pulled apart at their cetromeres by the aster spindle fibers
b. cell begins to elongate in shape; other aster spindle fibers push on each other
4. Telophase/Cytokinesis
a. cleavage furrow forms (cells begin to divide)
b. nuclear membrane forms around decondensed chromosomes
c. cell division