Lecture notes for Chapters 4 - 6

Hi, All.

Here are my notes for Chapters 4 - 6. Once again, the formating is a little strange, but it's still legible. If I every get a few spare moments, I'll edit the format. In the meantime, I hope they help with studying.

TR

Biol 1610
Chapter 4 Outline
Organization of the Cell

I. Cell theory.
A. What are the major statements of the cell theory?
1. Cells are the basic living units of organization and function in all organisms.
2. All cells come from other cells.
B. Be able name the 19th century biologists who are primarily responsible for formulating and stating cell theory.
1. Two German scientists - inductive reasoning that all plants and animals consist of cells
a. Inductive reasoning - begin with specific observations and draw a conclusion or discover a general principle.
b. Matthias Schleiden, botanist, 1838
c. Theodor Schwann, zoologist, 1839
2. Rudolf Virchow, 1855, observed dividing cells - proposed that new cells form only by division of previously existing cells
3. August Weismann, 1880, biologist - ancestry of all cells alive today can be traced back to ancient times
2. What features or abilities do all cells have in common?
A. Organization basically similar
1. Plasma membrane - chemical composition different inside than outside
2. Organelles - most have internal structures that are specialized to carry out metabolic activities
3. DNA concentrated in one area
B. Cell size is limited
1. Cells are small
2. Homeostasis - transport of materials in and out to maintain a constant internal concentration
3. Surface area to volume ratio
! As a cell gets bigger, its volume increases faster than surface area
! Less surface area for import/export - more distance to the center
! Can’t regulate its concentration of various ions
! Can’t efficiently export wastes
! Can’t transport needed molecules fast enough to sustain the cell
! Long and skinny, projections, all increase surface area

II. Major parts of a prokaryotic cell
A. Plasma membrane
1. Lipid bilayer that encloses the cells - separates outside from inside
2. Maybe infolded to form a complex of membranes along which many of the cell’s metabolic reactions take place
B. Nucleoid/nuclear area
1. Area in the cell where DNA is located/concentrated
2. Not enclosed in a membrane
C. Cytoplasm
1. Part of the cell inside the plasma membrane.
2. Cytosol is the fluid component
D. Ribosomes
1. Small complexes of ribonucleic acid and protein - polypeptide synthesis
2. Different sized subunits from eukaryotic ribosomes (16S)
E. Cell wall
1. Extracellular material that encloses the cell, including the plasma membrane
2. A few rare prokaryotic cells do not have a cell wall
F. Flagella
1. Long fibers that project from the cell and used in cell locomotion - propellers
2. Structure different from flagella in eukaryotic cells
III. Major parts of a eukaryotic cell (Table 4 - 1)
A. Plasma membrane

1. Lipid bilayer that encloses the cells - separates outside from inside
2. Several types of membranes are generally considered part of the internal membrane system or endomembrane system

B. Cell wall
1. Extracellular material that encloses the cell, including the plasma membrane
2. Not found in all eukaryotic cells - mainly fungi and plants
C. Nucleus
1. Membrane enclosed organelle which contains DNA.
2. Usually most prominent organelle in cell
3. Eukaryotic means “true nucleus.”
4. Nuclear envelope

a. Encloses DNA - ‘packed’ in chromatin 6 chromosomes when the cell is ready to divide.
b. Two concentric membranes that separate the nuclear contents from the surrounding cytoplasm.
c. Nuclear pores - membranes come together to form, consist of protein complexes - regulate the passage between nucleoplasm & cytoplasm.
d. Messenger RNA (mRNA) - synthesised in the nucleus and is transported out of the nucleus into the cytoplasm by the nuclear pores.
5. Nuclear lamina
a. Network of protein filaments form an inner lining for the nuclear envelope.
b. Give support, give shape.
c. May have other functions, such as organizing the contents of the nucleus.
6. Nucleoli/nucleolus - compact structures inside nucleus, not membrane inclosed.
a. Nucleolar organizer - inside nucleolus, made up of chromosomal regions containing instructions for making the type of RNA in ribosomes.
b. Ribosomal RNA synthesized in the nucleolus

D. Cytoplasm
1. Part of the cell inside the plasma membrane but outside of the nucleus.
2. Includes all the organelles outside the nucleus.
3. Cytosol is the fluid component.
E. Ribosomes
1. Found free in cytoplasm or bound to membranes.
2. Small complexes of ribonucleic acid and protein - polypeptide synthesis
3. Different sized subunits from prokaryotic ribosomes
4. Two subunits, one large and one small
F. Endoplasmic Reticulum (ER)

1. Parallel internal membranes that encircle nucleus and extend into may regions of the cytoplasm
2. ER lumen - internal space the membranes enclose
3. Membrane serves as a framework for enzymes that carry out sequential biochemical reactions
4. Different sizes & types in different cells

a. Rough ER

! Outer surface studded with ribosomes - bound ribosomes
! Central role in synthesis and assembly of proteins - for export from cell or those destined for other organelles
! Tunnel within the ribosome connects to an ER pore

! Within lumen, proteins are assembled, maybe modified (carbs or lipids)
! Molecular chaperones - aid in folding, transport of misfolded proteins to cytosol where proteasomes chop up the misfolded proteins
! Transport vesicles - small vesicles bud off, got to various sites in the cell

b. Smooth ER

! Tubular, smooth appearance
! Synthesis of many carbohydrates
! Primary site for synthesis of phospholipids & cholesterol
! In liver, important in glycogen breakdown
! Detox site in liver

G. Golgi complex/Golgi body/Golgi apparatus

1. Processes, sorts, & modifies proteins
2. Stacks of flattened membranous sacs called cisternae (cisterna)
3. One or many, depending on the cell
4. Each sac has an internal space or lumen - some separate, some connected
5. Three areas:

a. cis face - entry surface, nearest to nucleus, receives product from ER
b. trans face - exit surface, closest to plasma membrane, packages molecules in vesicles & transports them out of the Golgi
c. medial region - between cis and trans faces

6. General pathway -

a. Correctly formed proteins from ribosomes ER lumen
b. Vesicles move along the microtubules
c. cis face of the Golgi
d. Modified within the Golgi - carbs modified, signal molecules
e. Packaged into vesicles in the trans face
f. Pinched off and transported to specific destination - secreted, stored, transported within cell

H. Vesicles - small membrane bound sacs, pinched off of larger membranes
I. Lysosomes

1. Small sacs of digestive enzymes dispersed in the cytoplasm of most animal cells
2. Enzymes operate at rather acidic conditions - pH 5
3. Excellent example of benefits of separating functions within the cell by membranes - if enzymes loose in cell, do damage.
4. Break down bacteria, debris, old organelles
5. Primary lysosomes - bud off the Golgi, hydrolytic enzymes synthesized in the rough ER.
6. Bacteria enclosed in vesicles pinched off from plasma membrane
7. When two fuse, form secondary lysosomes
8. Tay-Sachs disease, in which a normal lipid cannot be broken down in brain cells - lipid accumulates and causes mental retradation, blindness, and death before age 5.

J. Peroxisomes

1. Membrane-enclosed organelles containing enzymes that catalyze an assortment of metabolic reactions in which hydrogen is transferred to oxygen.
2. During these reactions, they produce hydrogen peroxide
3. Hydrogen peroxide can be used to detoxify certain compounds, but would cause damage to the cell is released.
4. Peroxisomes contain catalase
5. Found in large numbers in cells that synthesize, store, or degrade lipids. One of their functions is to break down fatty acid molecules.
6. Synthesis certain phospholipids that are components of the insulating coverings of nerve cells.
7. Break down alcohol and other toxins
8. Specialized peroxisomes in plants called glyoxysomes convert stored fats to sugars
K. The Endomembrane system

1. Group of membranous structures in eukaryotic cells that interact through direct connections or by vesicles
2. Includes the endoplasmic reticulium, outer membrane of the nuclear envelope, Golgi complex, lysosomes, and the plasma membrane
3. How are the various organelles which collectively make up this system structurally and functionally related?

a. Structurally - connected either by direct connections or by vesicles

b. Functionally - all involved with enzymatic reactions: making and or breaking down cell products

K. Vacuoles

1. Large fluid-filled sacs with a variety of functions

2. Found in plants and yeasts, fills the function of lysosomes - break down wastes, old organelles
3. Wastes recycled in vacuoles or are stored
4. Plants, increase size of cell by addition of water
5. High concentration of solutes, water flows in, hydrostatic pressure - turgor pressure - mechanical strength of plant cells
6. Maintain pH, takes in excess H+
7. Unicellular protists
a. Food vacuoles - fuse with lysosomes to digest food
b. Contractile vacuoles - remove excess water from the cell
L. Mitochondria
1. Serial endosymbiosis
2. Function
a. Energy converting organelle - aerobic respiration
b. Affect health and aging - leak free radicals (toxic, highly reactive compounds with unpaired electrons)
c. Apoptosis - programed cell death vs necrosis, uncontrolled cell death, inflammation and neighboring cell damage
! Normal part of development and growth
! By interfering with energy metabolism or activating enzymes that mediate cell destruction
! Injured, large pores open up and leak cytochrome c
! Cytochrome c triggers apoptosis by activating caspases (enzymes) which cut up vital compounds in the cell
3. Structure
a. Like rod-shaped bacteria
b. Two membranes
c. Intermembrane space - compartment formed between the outer and inner mitochondiral membranes
d. Matrix - compartment enclosed by the inner mitochondrial membrane, contains enzymes that break down food molecules and convert them to chemical energy
e. Outer mitochondrial membrane - smooth and allows many small molecules to pass through it
f. Inner mitochondrial membrane - numerous folds (cristae/crista) and strictly regulates the types of molecules that can move across it. Cristae extend into the matrix and increase surface area - provide surface for matrix enzymes.
g. Mammalian - 5 - 10 identical, circular molecules of DNA, 1% of cell DNA
M. Chloroplasts
1. Similar to mitochondrion - serial endosymbiosis
2. Function
a. Convert light energy into chemical (ATP) energy
b. Chlorophyll - Photosynthesis
c. Carotenoids - light absorbing yellow and orange pigments
3. Structure
a. Typically disc-shaped
b. Two membranes
c. Outer membrane
d. Inter membrane
e. Intermembrane space
f. Stroma - space enclosed by inner membrane, contains enzymes that convert CO2 + H2O into sugars
g. Thylakoids -system of internal membranes, consist of interconnected set of flat disc-like sacs. Chlorophyll on thylakoid membrane, involved in ATP synthesis
h. Grana (granum) - stacks of thylakoids
i. Thylakoid lumen - inner most compartment of chloroplast
4. Plastids

a. Plastids - chloroplasts belong to a group of organelles known as plastids that produce and store food materials in cells of plants and algae
b. Proplastids - all plastids develop from, precursor organelles, sort of a plant stem cell, develop into a variety of plastids
c. Chloroplasts - develop when exposed to light
d. Chromoplasts - contain pigments that give some flowers and fruits their color - attract pollinators or seed disersers
e. Leucoplasts - unpigmented plastids, include amyloplasts which store starch in many seeds, roots, & tubers (potatoes)

N. Cytoskeleton - dense network of protein fibers, gives cells mechanical strength, shape, and ability to move, functions in cell division and internal cell transport
1. Microtubles
a. Function

! Structural role in cytoskeleton
! Involved with movement of chromosomes during cell division
! Serve as tracks for several other kinds of intracellular movement
! Major structural components of cilia and flagella

b. Structure

! Thickest filaments of the cytoskeleton
! Rigid, hollow rods about 25nm in outside diameter and up to several micrometers in length
! α-tubulin & β-tubulin dimers
! Elongates by addition
! Plus & minus ends, plus end elongates more rapidly

c. Microtubule-associated proteins (MAP’s)
d. Structural MAP’s - may help regulate microtubule assembly, cross-link microbules to theer cytoskeletal polymers
e. Motor MAP’s - use ATP enery to produce movement
f. Kinesin - motor protein moves organelles toward the plus end
g. Dynein - motor protein moves organelles toward the minus end, retrograde transport
h. Microtubule-organizing centers (MTOCs) - minus ends of microtubules appear to be organized in regions called
i. Centrosomes - in animal cells, main MTOC in the cell center
j. Centrioles - two structures in most centrosomes, 9X3 structures at right angles to each other - duplicated before cell division. Not found in all eukaryotic cells, mostly animal cells
k. Mitotic spindle - much of cytoskeleton disassembles during cell division, tubulin subunits organize into mitotic spindle, frame work for orderly distribution of chromosomes during cell division

l. Flagella - long (~200um) and relatively few extensions from the cell surface. 9+2 arrangement of microtubules. Dynein proteins and ATP facilate movement. Whip-like movement, perpendicular to cell surface.
m. Cilia - short (2-10 um) and many extensions from the cell surface. 9+2 arrangement of microtubules. Dynein proteins and ATP facilate movement. Oar-like movement, parallel to cell surface.
n. Basal body - anchor at base of flagella and cilia, under plasma membrane, 9x3 structure, organizes beginning growth of flagella and cilia but growth proceeds faster at ends. Replicates self, appears to be related to centrioles.

2. Microfilaments/actin filaments

a. Function

! Provide mechanical support for various cell structures
! Helps determine cell shape
! Generate movement by rapidly assembling and disassembling, sliding
b. Structure

! Flexible, solid fibers about 7nm in diameter
! Two intertwined polymer chains of actin molecules
! Linked with one another and other proteins by linker proteins - form bundles of fibers

c. Cell cortex - network of microfilaments visible just inside the plasma membrane, gel-like consistency, helps determine shape of cell
d. Myosin - filements composed of myosin associate with microfilaments.
e. Muscle cells - ATP binds to myosin, hydrolyzed to ADP, myosin binds to microfilaments and causes microfilaments to slide, contracting muscle cell
f. Dividing cells - ring of actin associated with myosin constricts the cell, forming two daughter cells
g. Pseudopodia - actin filaments push plasma membrane outward, contractions at other end, cytoplasm moves in direction of ‘push’
h. Microvilli - projections of plasma membrane that increases surface area
3. Intermediate filaments
a. Function

! Provide mechanical strength
! Help stabilize cell shape
! Abundant in regions that experience mechanical stress applied from outside the cell - prevent cell from stretching excessively in response to outside forces

b. Structure

* Tough, flexible fibers about 10nm in diameter * Certain proteins cross-link intermediate filaments with other types of filaments and mediate interactions between them
* Only found in some animal groups, including vertebrates, have intermediate filaments
* Vary widely in protein composition and size among different cell types, different organisms - keratins, neutrofilaments

O. Mention Integrins
1. Extracellular matrix (ECM)
a. Animals are surrounded by a gel of carbohydrates and fibrous proteins.
b. Secreted by the cell.
c. Function help the cell interact with the outside, give support to tissues.
2. Integrins
a. Proteins that serve as membrane receptors for the ECM - active in cell signaling
b. May be important in cell movement and in organizing the cytoskeleton so the cells assume a definite shape.
c. In some cells, anchor the ECM to the to the intermediate filaments and microfilaments of the internal cytoskeleton.



Chapter 5
Outline
Biological Membranes

I. Structure of a ‘typical’ biological membrane according to the fluid mosaic model
A. Phospholipid bilayer
1. General function a. Separate outside from inside - selectively permeable membrane
b. Spontaneously round up and form vesicles
c. Flexible - able to bend/change shape without breaking
B. Membrane proteins
1. General functions
a. Anchoring - anchor to extracellular matrix, attach to microfiliments within the cell (integrins)
b. Passive transport
c. Active transport
d. Enzymatic activity - catalyze activity within or on surface
e. Signal transduction - bind to receptors and pass information into the cell
f. Cell recognition - proteins recognized by cell/organism as self or non-self (MHC), antigens (destruction) vs tissue bonding
g. Intercellular junctions - attachment of cells to each other
2. Types of membrane proteins
a. Integral - firmly bound to the membrane, amphipathic
b. Transmembrane - integral proteins that extend completely through the membrane
• α-helixes most common transmembrane structure - hydrophobic amino acid side chains

• β-pleated sheets may roll up to form a barrel shape - pores

c. Peripheral - not firmly bound to the membrane, on outside or inside, usually noncovalently bound to exposed regions of integral proteins
3. How they get to the membrane
a. Outer surface membrane proteins - synthis is rough ER, sugars added in lumen (glycoproteins), transported to the Golgi, further modification, transport to plasma membrane
b. Inside (lumen of ER, Golgi, inside of vesicle) becomes outside of cell


II. Diffusion
A. Definition - physical process based on random motion

1. Atoms and molecules possess kinetic energy/energy of motion
2. Solids - atoms/molecules tightly packed, attractions allow for vibration only
3. Liquid - atoms/molecules farther apart, attractions are weaker, particles move about with considerable freedom
4. Gas - particles so far apart that intermolecular forces are negligible, movement only restricted by walls of container

5. Concentration gradient - areas of higher and lower concentration
6. Molecules will randomly move ‘down’ a concentration gradient, from higher to lower concentration

B. Example with blue dye in water, peeled orange
C. Physical properties that affect the diffusional rate of a molecule

1. Size
2. Shape
3. Electric charges
4. Temperature

D. Simple diffusion in the cell - small, uncharged/nonpolar molecules move directly through the membrane down their concentration gradient

1. Oxygen and carbon dioxide move by simple diffusion
2. Rate affected by concentration - higher the concentration on one side, the faster the diffusion down the gradient
3. No initial energy cost to the cell - cost comes from maintaining the gradient


III. Osmosis
A. Definition - net movement of water (principal solvent in a cell) through a selectively permeable membrane

1. Water can diffuse freely
2. Most solutes, such as sugars, salt, etc. cannot
3. Solutes bind water on one side of the membrane, so water doesn’t move freely
4. Water on other side free to move, moves down the gradient

B. Response of an animal cell (no cell wall) to following types of solutions:

1. Isotonic - no change, ion concentration same on both sides
2. Hypertonic - water flows out, cell becomes dehydrated and shrunken
3. Hypotonic solution - water flows in, cell swells or bursts

C. Response of a plant cell (cells with cell walls) to following types of solutions:

1. Isotonic - no change, ion concentration same on both sides
2. Hypertonic - water flows in, vacuole fills, plant fully turgid - healthy
3. Hypotonic - water flows out, become plasmolyzed & eventually dies


IV. Facilitated diffusion - a specific transport protein makes the membrane permeable to a particular solute. Always down the concentration gradient.
A. Channel proteins - form hydrophilic channels through the membrane

1. Porins - form rather large tunnels through which water and other solutes pass
2. Ion channels/gated channels - form narrow channels that transport specific ions down their gradients/electrochemical gradients, gated because they can open and close

B. Carrier proteins - bind to solute(s) on one side of the membrane, change shape, and release solute(s) on other side

1. Carrier mediated transport is slower than channel proteins but faster than by simple diffusion
2. Glucose transporter 1 (GLUT 1) transports glucose down the concentration gradient into RBCs
3. Higher concentration in blood than in cell
4. Binding the glucose changes the shape of GLUT 1 - releasing the glucose into the cytoplasm
5. ATP not consumed in conformational change
6. Once in cell, RBC phosphorylates the glucose - charged, different shape, no longer ‘part’ of the gradient


V. Active transport

A. Some times the cell needs solutes in greater concentration than are available outside the cell
B. Use active transport to move solutes into the cell against the concentration gradient

C. Similar to facilitated diffusion in that:

1. Membrane protein binds to a solute(s)
2. Binding the solute(s) cause a conformational change that releases the solute(s) into the cytoplasm

D. Differ in that:

1. Solutes are transported against the concentration gradient
2. Energy is consumed to transport the solute(s) into the cell - facilitated diffusion uses energy once the solute is in the cell, not to bring it in.
3. Direct active transport - ATP binds to the transport protein to provide energy for the transport
4. Indirect active transport - concentration gradient provides energy for the cotransport of some other substance, such as an ion
a. Sodium-potassium pump example. Fig 5 - 17, page 121

b. Because fewer potassium are imported vs sodium exported, inside cell is negatively charged
c. Membrane is polarized - establishes an electrochemical gradient across the membrane
d. Energy from the electrochemical gradient used to power other reactions - will get into in ATP generation inside mitochondria

E. What is a cotransport system?

1. Moves solutes across the membrane by indirect active transport
2. Carrier cotransports a solute against its concentration gradient while sodium, potassium, or hydrogen ions move down their concentration gradients
3. ATP energy produces the concentration gradient that powers the cotransport
4. Example of transport of glucose against its concentration gradient (starvation conditions, different part of the cell) by cotransportation of sodium down its concentration gradient. Fig 5 - 19, page 123. Meanwhile, the sodium-potassium pump is maintaining the Na concentration higher outside the cell.


VI. Exocytosis & Endocytosis

A. Diffusion (simple and facilitated) and carrier-mediated transport - individual molecules & ions transported
B. Exocytosis and endocytosis - large amounts, large molecules, small cells transported
C. Exocytosis and endocytosis both considered active transport

D. Exocytosis -

1. Ejection of waste products, hormones, etc., by fusion with the plasma membrane
2. Growth of the plasma membrane - addition

E. Endocytosis

1. Materials taken into the cell
2. Phagocytosis (cell eating)
a. Large solid particles bind to membrane
b. Enclosed by folds of membrane
c. Pinched off into a vesicle
d. Fuse with lysosomes
e. Particle degraded
4. Pinocytosis (cell drinking)
a. Cell takes in dissolved materials.
b. Tiny droplets trapped in folds of membrane
c. Pinch off into cytosol
d. Liquid contents slowly transferred to cytosol - vesicles become progressively smaller

F. Receptor-mediated endocytosis

1. Specific molecules combine with receptor proteins in the plasma membrane
2. Main mechanism by which cells take in macromolecules
3. Low-density lipoprotein transport example. Fig 5-23, page 126.

a. Cell makes LDL receptors, concentrate in a clathrin coated pit
b. LDL (the ligand) binds to the receptors
c. Coated pit becomes a coated vesicle
d. Clathrin removed - uncoated vesicle
e. Vesicles fuse with endosomes
f. LDL released from receptor
g. Receptors pinch off into a different vesicle, return to plasma membrane
h. LDL containing vesicle fuses with a lysosome, LDL degraded
i. Cholesterol released into the cytosol


VII. Cell connections

A. Cells close to each other typically develop intercellular junctions
1. Form strong connections
2. Prevent passage of materials
3. Establish rapid communications with each other

B. Tight junctions - animal cells

1. Seal off intercellular spaces between cells
2. Substances can not leak between them
3. Plasma membranes of the two cells in contact - proteins link/pass through both
4. Intermittent connections - not entire surface of plasma membrane
5. Intestinal lining, brain-blood barrier

C. Desmosomes - animal cells

1. Points of attachment - anchoring junction
2. Hold cells together like a rivet or spot weld - strength
3. Do not affect passage of materials between them
4. Structure

a. Dense disks on cytoplasm side of cell
b. Disks connected/anchored to intermediate filaments inside cell
c. Protein filaments cross the narrow intercellular space
d. Intermediate filaments networks connected across desmosomes, stress distributed across tissue

D. Gap junctions - animal cells

1. Like desmosome - spans space between cells but smaller
2. Contain channels that connect cytoplasm of adjacent cells
3. Connexin - integral membrane protein
4. Cluster of six connexin forms cylinders - join with connexin cylinder on other side, forms channel between cells but not to outside of cell
5. Channel can be opened and closed - fixed diameter open
6. Allows passage of small molecules (ions) and some regulatory molecules (cyclic AMP)
7. Provide for rapid chemical and electrical communication between the cells
a. Pancreatic cells (signaling to release insulin) & cardiac muscle cells (contract in unison)

E. Plasmodesmata - plants

1. Because have cell walls, don’t need desmosomes for strength
2. Cell walls isolate the cells
3. Plasmodesmata are channels about 20 - 40 nm wide through adjacent cells walls, connect cytoplasm
4. Plasmotubule - narrow cylindrical structure that runs through plasmodesmata and connects smooth ER of the two cells
5. Allows for passage of molecules and ions but not organelles
6. Allows for a type of slow electrical signaling in plants
7. Plasmodesmata channels can be dilated




Chapter 6 Outline
Cell Communication

General cell signaling (See Figure 6-2, page 136)
I. Signal of some sort is sent
A. Direct contact
1. Some immune cells - make direct contact and ligand on one cell binds to receptor on target cell
B. Local regulators
1. Signaling molecule that diffuses through the interstitial fluid and acts on neighboring cells
2. Called paracrine regulation
3. Types of local regulators:
a. Growth factors - typically peptides, stimulate cell division and normal development in specific cell types
b. Histamine - stored in E cells (check) and are released in response to allergic reactions, injury, infection, cause blood vessels to dilate and capillaries to become more permeable - allow passage of responding cells
c. Prostaglandins - modify cAMP levels and interact with other signaling molecules to either contract or relax smooth muscle
d. Nitric oxide - gas, many functions including dilation of blood vessels, decreasing blood pressure
C. Neurotransmitters
1. Chemical compounds released by neurons to signal one another
2. Diffuse across synapses - gaps between the neutrons
D. Hormones/long distance
1. Chemical messengers secreted by endocrine glands

1. No ducts - secreted into interstitial fluid, diffuse into capillaries
2. Transported by blood to target cells


II. Signal is received by target cell - signal molecule binds to membrane receptor or intracellular receptor and activates the receptor
A. Membrane receptors

1. Genes in cell code for specific receptors to be expressed on surface of the cell - proteins or glycoproteins
2. Recognize a specific ligand from a signaling cell - ligand is generally hydrophilic
3. 3 domains - domain is a structural and functional region of the protein
4. Receptor domains:

a. External docking domain - interacts with the ligand
b. Transmembrane domain
c. Intracellular ‘tail’ domain - transmits the signal within the cell

5. Types of membrane receptors (page 139) - all transmembrane proteins

6. Ion channel-linked receptors/ligand-gated channels

a. Converts chemical signals into electrical signals
b. Receptor may serve as the channel - opens or closes in response to binding of the ligand
c. Example: Acetylcholine

• Neurotransmitter that binds to an acetylcholine receptor - ligand-gated sodium ion channel
• Sodium channel opens, causing influx of sodium into the cell
• Decreases electric charge difference across the membrane (depolarization) which leads to muscle contraction

2. G-protein-linked receptors/G protein-coupled receptors

a. Transmembrane proteins that loop back and forth through the membrane 7 times - α-helixes
b. Intracellular portion (loops) have a binding site for a specific G-protein
c. G-proteins bind GTP, change shape, interact with another signal transduction protein
d. Discuss G-proteins more with signal transduction

3. Enzyme-linked receptors

a. Function directly as enzymes or are linked to enzymes
b. External binding site for ligand, enzyme component inside the cell
c. Example: Tyrosine kinases
• Bind growth factors
• Tyrosine kinases phosphorylates tyrosine residues on signal transduction protein(s) inside cell
• Phosphorylation - transfer of the terminal phophate group from an ATP molecule to the hydroxyl group on a target protein. In this case, the tyrosine residue of the target protein is phosphorylated.
• Phosphorylations changes shape of the target molecule, cause a new behavior or activation of behavior

B. Intracellular receptors
1. Some signaling molecules are small, hydrophobic molecules
2. Diffuse through plasma membrane and bind with an intracellular receptor
3. Most intracellular receptors are transcription factors, proteins that regulate the expression of specific genes
4. Examples: cortisol, sex hormones, Vitamins A & D, nitric oxide

III. Signal transduction
A. Ion-gated/ligand gated receptor transduction - change in electrical potential of the membrane caused the signal transduction
B. G-proteins
1. In group called first messengers
2. Inactive state, three subunits
3. One subunit bound to GDP (guanine diphosphate) - inactive state
4. Ligand binds receptor, receptor causes GDP to be released from subunit
5. GDP replaced with GTP and disassociates from other subunits - associates with second messenger
6. G-protein subunit is a GTPase - catalyzes conversion of GTP to GDP, returns to inactive state bound to other two subunits
C. Second messengers
1. Ions or small molecules that relay signal inside the cell
2. Second messengers may be produced in large amounts from one receptor-ligand interaction, amplifying the signal
3. Diffuse through cytosol or membrane to next target
4. Signaling cascade - a chain of molecules in the cell that relays signal
5. Second messenger examples:
a. Ca2+ ions - Ca2+ gates open, allow influx of Ca2+, Ca2+ binds to calmodulin, calmodulin changes shape and activates other enzymes
b. Phospholipids - G-protein activates membrane-bound phopholipase C, splits membrane phopholipid PIP2 into IP3 and DAG, both second messengers
c. cAMP (page 141)

• G-protein GTPase subunit interacts with adenylyl cyclase
• Adenylyl cyclase converts ATP to cAMP
• cAMP interacts with next target molecule, could be an enzyme that alters metabolism, a protein that alters gene activity, or a protein that opens or closes ion channels
• cAMP activates protein kinase A - protein kinase A physphoylates other molecules

D. Scaffolding proteins

1. Increase efficiency of the signal cascade
2. Organize the intracellular signaling molecules into signaling complexes
3. Position enzymes close to their substrates



IV. Response of the target cell
A. Ion channels open or close
B. Enzyme activity is altered - metabolic change or other effects
C. Specific gene activity may be turned on or off - changes in cell shape, growth, cell division, cell differentiation
D. Signal termination

1. Signal must be stopped or cell can’t respond to new signals
2. Returns receptor and signal transduction components back to the inactive state
3. Phosphorylated enzymes dephosporylated, etc.

E. Example of cell responce: Cholera

1. Normal scenario:

a. Ligand bonds to receptor in intestinal cell
b. Receptor activates G-protein
c. G-protein activates Adenylyl cyclase
d. Andenylyl cyclase converts ATP to cAMP
e. cAMP activates ion channel which allows chlorine ions into the intestine
f. Water follows

2. Cholera:

a. Toxin activates G-protein but doesn’t allow conversion of GTP to GDP - G-protein always on
b. Chlorine ions flood the intestine along with water
c. Patient dies of dehydration caused by sever diarrhea