c ells chapter 3. cell theory cell: structural and functional unit of life organismal functions...
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Cell Theory
• Cell: structural and functional unit of life • Organismal functions depend on individual
and collective cell functions• Biochemical activities of cells dictated by their
shapes or forms, and specific subcellular structures
• Continuity of life has cellular basis
Cell Diversity
• Over 200 different types of human cells
• Types differ in size, shape, subcellular components, and functions
Plasma Membrane
• Bimolecular layer of lipids and proteins in a constantly changing fluid mosaic
• Plays a dynamic role in cellular activity• Separates intracellular fluid (ICF) from
extracellular fluid (ECF)– Interstitial fluid (IF) = ECF that surrounds cells
Membrane Lipids
• 75% phospholipids (lipid bilayer)– Phosphate heads: polar and hydrophilic– Fatty acid tails: nonpolar and hydrophobic
• 5% glycolipids– Lipids with polar sugar groups on outer membrane surface
• 20% cholesterol– Increases membrane stability and fluidity
• Lipid Rafts– ~ 20% of the outer membrane surface– Contain phospholipids, sphingolipids, and cholesterol– May function as stable platforms for cell-signaling molecules
Membrane Proteins• Integral proteins
– Firmly inserted into the membrane (most are transmembrane)
– Functions: Transport proteins (channels and carriers), enzymes, or receptors
• Peripheral Proteins– Loosely attached to integral proteins – Include filaments on intracellular surface and
glycoproteins on extracellular surface– Functions: Enzymes, motor proteins, cell-to-cell links,
provide support on intracellular surface, and form part of glycocalyx
Figure 3.3
Integralproteins
Extracellular fluid(watery environment)
Cytoplasm(watery environment)
Polar head ofphospholipid molecule
Glycolipid
Cholesterol
Peripheralproteins
Bimolecularlipid layercontainingproteins
Inward-facinglayer ofphospholipids
Outward-facinglayer ofphospholipids
Carbohydrate of glycocalyx
Glycoprotein
Filament of cytoskeleton
Nonpolar tail of phospholipid molecule
= lipid= protein
Cell Junctions• Some cells "free”• Some bound into communities– Three ways cells are bound:• Tight junctions • Desmosomes • Gap junctions
Tight Junctions• Adjacent integral proteins fuse form
impermeable junction encircling cell– Prevent fluids and most molecules from moving
between cells
Desmosomes• Anchor cells together at
plaques (thickenings on plasma membrane)– Linker proteins between cells
connect plaques– Keratin filaments (part of the
cytoskeleton) extend through cytosol to opposite plaque giving stability to cell
– Reduces possibility of tearing
Gap Junctions• Transmembrane
proteins form pores (connexons) that allow small molecules to pass from cell to cell– For spread of ions,
simple sugars, and other small molecules between cardiac or smooth muscle cells
Cell Cycle• Defines changes from formation of cell until it
reproduces• Includes:– Interphase– Cell division (mitotic phase)
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Interphase
• Period from cell formation to cell division• Nuclear material called chromatin• Three subphases:– G1 (gap 1)—vigorous growth and metabolism• Cells that permanently cease dividing said to be in G0
phase
– S (synthetic)—DNA replication occurs– G2 (gap 2)—preparation for division
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InterphaseCentrosomes (eachhas 2 centrioles)
Plasmamembrane
Nucleolus
Nuclearenvelope
Chromatin
Cell Division
• Meiosis - cell division producing gametes• Mitotic cell division - produces clones– Essential for body growth and tissue repair– Occurs continuously in some cells
• Skin; intestinal lining– None in most mature cells of nervous tissue,
skeletal muscle, and cardiac muscle• Repairs with fibrous tissue
Events Of Cell Division
• Mitosis—division of nucleus– Four stages • Prophase• Metaphase• Anaphase• Telophase
– Cytokinesis—division of cytoplasm-by cleavage furrow
Telophase and Cytokinesis
Telophase Cytokinesis
Nuclearenvelopeforming Nucleolus forming
Contractilering atcleavagefurrow
Control of Cell Division• "Go" signals:– Critical volume of cell when area of membrane
inadequate for exchange– Chemicals (e.g., growth factors, hormones)– Availability of space–contact inhibition
• To replicate DNA and enter mitosis requires– Cyclins–regulatory proteins
• Accumulate during interphase
– Cdks (Cyclin-dependent kinases)–bind to cyclins activated• Enzyme cascades prepare cell for division
– Cyclins destroyed after mitotic cell division
Control of Cell Division• Checkpoints– G1 checkpoint (restriction
point) most important• If doesn't pass G0–no
further division
– Late in G2 MPF (M-phase promoting factor) required to enter M phase
• "Other Controls" signals– Repressor genes inhibit cell
division• E.g., P53 gene
Roles of the Three Main Types of RNA
• Messenger RNA (mRNA)– Carries instructions for building a polypeptide, from
gene in DNA to ribosomes in cytoplasm• Ribosomal RNA (rRNA)– A structural component of ribosomes that, along with
tRNA, helps translate message from mRNA• Transfer RNAs (tRNAs)– Bind to amino acids and pair with bases of codons of
mRNA at ribosome to begin process of protein synthesis
Transcription
• Transfers DNA gene base sequence to a complementary base sequence of an mRNA
• Transcription factor– Loosens histones from DNA in area to be
transcribed– Binds to promoter, a DNA sequence specifying
start site of gene to be transcribed– Mediates the binding of RNA polymerase to
promoter
Transcription
• RNA polymerase– Enzyme that oversees synthesis of mRNA– Unwinds DNA template– Adds complementary RNA nucleotides on DNA
template and joins them together– Stops when it reaches termination signal– mRNA pulls off the DNA template, is further
processed by enzymes, and enters cytosol
Figure 3.35
RNA polymerase
RNA polymerase
RNApolymerase
DNA
Coding strand
Template strandPromoterregion
Terminationsignal
mRNA
mRNA
Template strand
mRNA transcript
Completed mRNA transcript
Rewindingof DNA
Coding strand of DNA
DNA-RNA hybrid region
The DNA-RNA hybrid: At any given moment, 16–18 base pairs ofDNA are unwound and the most recently made RNA is still bound toDNA. This small region is called the DNA-RNA hybrid.
Templatestrand
Unwindingof DNA
RNA nucleotides
Direction oftranscription
Initiation: With the help of transcription factors, RNApolymerase binds to the promoter, pries apart the two DNA strands,and initiates mRNA synthesis at the start point on the template strand.
Termination: mRNA synthesis ends when the termination signalis reached. RNA polymerase and the completed mRNA transcript arereleased.
Elongation: As the RNA polymerase moves along the templatestrand, elongating the mRNA transcript one base at a time, it unwindsthe DNA double helix before it and rewinds the double helix behind it.
1
2
3
Transcription
Translation
• Converts base sequence of nucleic acids into the amino acid sequence of proteins
• Involves mRNAs, tRNAs, and rRNAs• Each three-base sequence on DNA is
represented by a codon – Codon—complementary three-base sequence on
mRNA– Each codon corresponds to a specific amino acid
Translation
• mRNA attaches to a small ribosomal subunit that moves along the mRNA to the start codon
• Large ribosomal unit attaches, forming a functional ribosome
• Anticodon of a tRNA binds to its complementary codon and adds its amino acid to the forming protein chain
• New amino acids are added by other tRNAs as ribosome moves along rRNA, until stop codon is reached
Role of Rough ER in Protein Synthesis
• mRNA–ribosome complex is directed to rough ER by a signal-recognition particle (SRP)
• Forming protein enters the ER• Sugar groups may be added to the protein,
and its shape may be altered• Protein is enclosed in a vesicle for transport to
Golgi apparatus
Figure 3.39
Ribosome
ER signalsequence
The mRNA-ribosome complex isdirected to the rough ER by the SRP.There the SRP binds to a receptor site.
Once attached to the ER, the SRP is releasedand the growing polypeptide snakes through theER membrane pore into the cisterna.
The signal sequence is clipped off by anenzyme. As protein synthesis continues, sugargroups may be added to the protein.
In this example, the completedprotein is released from the ribosomeand folds into its 3-D conformation,a process aided by molecular chaperones.
The protein is enclosed within aprotein (coatomer)-coated transportvesicle. The transport vesicles maketheir way to the Golgi apparatus,where further processing of theproteins occurs (see Figure 3.19).
Signalrecognitionparticle(SRP)
Receptor site
mRNA
Growingpolypeptide
Signalsequenceremoved
Sugargroup
Releasedprotein
Transport vesiclepinching off
Coatomer-coatedtransport vesicle
Rough ER cisterna
Cytoplasm
1 2
3
4
5
Membrane Transport
• Plasma membranes are selectively permeable• Passive Processes– No cellular energy (ATP) required– Substance moves down its concentration gradient
• Active Processes– Energy (ATP) required– Occurs only in living cell membranes
Passive Processes
• Simple diffusion– Nonpolar lipid-soluble (hydrophobic) substances
diffuse directly through the phospholipid bilayer• Facilitated diffusion– Carrier or channel mediated
• Osmosis
Passive Processes: Facilitated Diffusion
• Some lipophobic molecules (e.g., glucose, amino acids, and ions) use carrier proteins or channel proteins, both of which:– Exhibit specificity (selectivity)– Are saturable; rate is determined by number of
carriers or channels– Can be regulated in terms of activity and quantity
Facilitated Diffusion Using Carrier Proteins
• Transmembrane integral proteins transport specific polar molecules (e.g., sugars and amino acids)
• Binding of substrate causes shape change in carrier
Facilitated Diffusion Using Channel Proteins
• Aqueous channels formed by transmembrane proteins selectively transport ions or water
• Two types:– Leakage channels
• Always open
– Gated channels• Controlled by chemical or electrical signals
Passive Processes: Osmosis
• Movement of solvent (water) across a selectively permeable membrane
• Water diffuses through plasma membranes:– Through the lipid bilayer– Through water channels
called aquaporins (AQPs)
Passive Processes: Osmosis
• Water concentration is determined by solute concentration
• Osmolarity: total concentration of solute particles
• When solutions of different osmolarity are separated by a membrane, osmosis occurs until equilibrium is reached
• In Cells: When osmosis occurs, water enters or leaves a cell– Change in cell volume disrupts cell function
Tonicity
• Tonicity: The ability of a solution to cause a cell to shrink or swell
• Isotonic: A solution with the same solute concentration as that of the cytosol
• Hypertonic: A solution having greater solute concentration than that of the cytosol
• Hypotonic: A solution having lesser solute concentration than that of the cytosol
Membrane Transport: Active Processes
• Two types of active processes:– Active transport– Vesicular transport
• Both use ATP to move solutes across a living plasma membrane
Active Transport
• Requires carrier proteins (solute pumps)• Moves solutes against a concentration
gradient• Types of active transport:– Primary active transport– Secondary active transport
Primary Active Transport
• Hydrolysis of ATP (energy!) causes shape change in transport protein
• bound solutes (ions) are “pumped” across the membrane
• Sodium-potassium pump (Na+-K+ ATPase)– Located in all plasma membranes– Involved in primary (and secondary) active transport
of nutrients and ions– Maintains electrochemical gradients essential for
functions of muscle and nerve tissues
Secondary Active Transport
• Depends on an ion gradient created by primary active transport
• Energy stored in ionic gradients is used indirectly to drive transport of other solutes
• Cotransport—always transports more than one substance at a time– Symport system: Two substances transported in same
direction– Antiport system: Two substances transported in opposite
directions
Figure 3.11 step 1
The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell.
Na+-K+
pump
Cytoplasm
Extracellular fluid
1
Figure 3.11 step 2
The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell.
As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradientinto the cell. (ECF = extracellular fluid)
Na+-glucosesymporttransporterloadingglucose fromECF
Na+-glucosesymport transporterreleasing glucoseinto the cytoplasm
Glucose
Na+-K+
pump
Cytoplasm
Extracellular fluid
1 2
Vesicular Transport• Transport of large particles, macromolecules,
and fluids across plasma membranes• Requires cellular energy (e.g., ATP)• Functions:– Exocytosis—transport out of cell – Endocytosis—transport into cell– Transcytosis—transport into, across, and then out
of cell– Substance (vesicular) trafficking—transport from
one area or organelle in cell to another
Endocytosis and Transcytosis
• Involve formation of protein-coated (typically clathrin) vesicles
• Often receptor mediated, therefore very selective
http://www.biologycorner.com/resources/endocytosis.gif
Figure 3.12
Coated pit ingestssubstance.
Protein-coatedvesicledetaches.
Coat proteins detachand are recycled toplasma membrane.
Uncoated vesicle fuseswith a sorting vesiclecalled an endosome.
Transportvesicle containing
membrane componentsmoves to the plasma
membrane for recycling.
Fused vesicle may (a) fusewith lysosome for digestionof its contents, or (b) deliverits contents to the plasmamembrane on theopposite side of the cell(transcytosis).
Protein coat(typicallyclathrin)
Extracellular fluid Plasmamembrane
Endosome
Lysosome
Transportvesicle
(b)(a)
Uncoatedendocytic vesicle
Cytoplasm
1
2
3
4
5
6
Endocytosis
• Phagocytosis—pseudopods engulf solids and bring them into cell’s interior– Macrophages and some white blood cells
Endocytosis
• Fluid-phase endocytosis (pinocytosis)—plasma membrane infolds, bringing extracellular fluid and solutes into interior of the cell – Nutrient absorption in the small intestine
Endocytosis
• Receptor-mediated endocytosis— highly selective– Uptake of enzymes low-density lipoproteins, iron,
and insulin
Figure 3.13c
Vesicle
Receptor recycledto plasma membrane
(c) Receptor-mediatedendocytosisExtracellular substances bind to specific receptor proteins in regions of coated pits, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles.
Exocytosis
• Examples: – Hormone secretion – Neurotransmitter release – Mucus secretion – Ejection of wastes
Figure 3.14a
1 The membrane-bound vesicle migrates to the plasma membrane.
2 There, proteinsat the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins).
The process of exocytosisExtracellular
fluid
Plasma membraneSNARE (t-SNARE)
Secretoryvesicle
VesicleSNARE(v-SNARE)
Molecule tobe secretedCytoplasm
Fusedv- and
t-SNAREs
3 The vesicleand plasma membrane fuse and a pore opens up.
4 Vesiclecontents are released to the cell exterior.
Fusion pore formed
Membrane Potential
• Separation of oppositely charged particles (ions) across a membrane creates a membrane potential (potential energy measured as voltage)
• Resting membrane potential (RMP): Voltage measured in resting state in all cells – Ranges from –50 to –100 mV in different cells– Results from diffusion and active transport of ions
(mainly K+)
Figure 3.15
1
2
3
K+ diffuse down their steep concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face.
K+ also move into the cell because they are attracted to the negative charge established on the inner plasma membrane face.
A negative membrane potential(–90 mV) is established when the movement of K+ out of the cell equals K+ movement into the cell. At this point, the concentration gradient promoting K+ exit exactly opposes the electrical gradient for K+ entry.
Potassiumleakagechannels
Protein anion (unable tofollow K+ through themembrane)Cytoplasm
Extracellular fluid