The Cellular Level of Organization

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CHAPTER 3

• The Cellular Level of Organization

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INTRODUCTION

• A cell basic living, structural, functional
  unit of body
• Cytology study of cell structure
• Cell physiology study of cell function
• Generalized view of cell composite of many
  different cells
• No single cell includes all of the features seen
  in the generalized cell.

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PARTS of a CELL

• Cell can be divided into three principal parts
• Plasma (cell) membrane (PM)
• Cytoplasm
• Cytosol
• Organelles (except for the nucleus)
• Nucleus

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THE PLASMA MEMBRANE

• Flexible, sturdy barrier surrounding cytoplasm of
  cell
• Fluid mosaic model (Figure 3.2)
• Proteins in a sea of lipids
• Lipid bilayer (amphipathic)
• two back-to-back layers of PL molecules
• FA tail region NONpolar (hydrophobic)
• PO4-3 head region polar (hydrophilic)
• cholesterol
• glycolipids
• glyco sugar
• extracellular face only

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Arrangement of Membrane Proteins

• Integral proteins
• amphipathic
• anchored w/in membrane
• Peripheral proteins
• associated w/ head of PL or w/ integral protein
• can be removed from membrane
• glycoproteins
• CHO groups protrude into ECF
• glycocalyx

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Functions of Membrane Proteins

• Ion channels (integral)
• Transporters (integral
• Receptors (integral)
• Enzymes (integral or peripheral)
• Cell identity marker (glycoprotein)
• Linkers (integral and peripheral)

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Membrane Fluidity

• Mobility with structure
• movement w/in bilayer
• no flip-flop
• Dependent upon
• of double bonds in fatty acid tails of lipids
• amount of cholesterol present
• stabilizes membrane
• reduces fluidity _at_ normal body temp.
• Allows self-repair of lipid bilayer
• Enables many cellular processes
• assembly of membrane proteins
• cell movement, growth, etc.

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Membrane Permeability

• Selective permeability
• Permeable to small, nonpolar, uncharged molecules
  
• Permeable to water
• Impermeable to ions charged or polar molecules
• Increased by transmembrane proteins
• Macromolecules must cross PM via vesicular
  transport.

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Gradients Across PM

• Difference in concentration of a chemical or
  electrical charge between opposite sides of PM
• Concentration gradient
• Electrical gradient
• Electrochemical gradient
• Allow for movement of substances across PM
• downhill movement
• Oxygen Na more concentrated outside cell
• CO2 K more concentrated inside cell

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TRANSPORT ACROSS PM

• Downhill movement is passive
• Diffusion thru lipid bilayer
• Diffusion thru ion channels
• Facilitated diffusion
• Requires transporter (usually a protein)
• Uphill movement is active
• Requires cellular energy in form of ATP
• Substances can also enter or leave cell thru
  vesicle transport

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Principles of Diffusion

• Diffusion random mixing of particles that
  occurs in a solution as a result of the kinetic
  energy of the particles
• Occurs down concentration gradient
• Equilibrium eventually achieved
• Diffusion rate influenced by
• Steepness of the concentration gradient
• Temperature
• Size or mass of the diffusing substance
• Surface area
• Diffusion distance

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Diffusion Through Lipid Bilayer

• Nonpolar, hydrophobic molecules diffuse freely
• respiratory gases
• lipids
• small alcohols
• ammonia
• Important for gas exchange, absorption of some
  nutrients, excretion of some wastes

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Diffusion Thru Membrane Channels

• Most are ion channels
• small, inorganic (hydrophilic) ions
• Ion channels are selective
• gated or open all the time
• slower than free diffusion because site specific

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Osmosis

• Osmosis net movement of solvent through
  selectively permeable membrane
• In living systems the movement of water (the
  solute) from area of higher concentration to area
  of lower concentration across the membrane
  (Figure 3.6)

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Osmosis

• Water molecules penetrate membrane via diffusion
• through lipid bilayer
• through aquaporins
• transmembrane proteins that function as water
  channels
• Water moves from an area of lower solute
  concentration to an area of higher solute
  concentration.
• Occurs only when membrane is permeable to water
  but not to certain solutes

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Osmotic Pressure

• Force exerted on membrane by impermeable solute
• Proportional to solute that cannot cross
  membrane

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Tonicity

• Measure of solutions ability to change volume of
  cells by altering their water concentration
• Isotonic solution
• solute is same on both sides of PM
• RBCs maintain normal shape (Fig. 3.7a)
• Hypotonic solution
• solute in soln lower than inside cell
  (cytosol)
• Water flows into cell to equalize solute
• RBCs undergo hemolysis (Fig. 3.7b)
• Hypertonic solution
• solute in soln higher than inside cell
  (cytosol)
• Water flows out of cell to equalize solute
• RBCs undergo crenation (Fig. 3.7c)

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Facilitated Diffusion

• Transport of highly charged or polar solutes
  across PM
• Solute binds to specific transporter
• Transporter undergoes a conformational change
• Solute carried from one side of PM to other
• Saturable process
• Transport maximum
• Rate of facilitated diffusion dependent upon
• steepness of concentration gradient
• of transporter proteins available
• Transport of glucose, urea, fructose, galactose,
  some vitamins
• PASSIVE process!!

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Facilitated Diffusion of Glucose

• Glucose binds transport protein
• Transport protein ? shape
• Glc moves across PM (down concentration gradient)
• Kinase enzyme reduces glc inside cell
• glc-6-P unusable by cell
• Transporter proteins always bring glucose into
  cell

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Active Transport

• Moves solutes AGAINST concentration gradient
• Requires energy
• ATP (primary)
• Ion concentration gradient
• (secondary)
• Saturable process
• Ex Na/K pump (Fig 3.8)

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Primary Active Transport

• Na/K pump most prevalent (Figure 3.8)
• Energy derived from ATP hydrolysis
• Maintains low Na and high K in cytosol
• 3 Na bind transporter (intracellular side of PM)
• ATP hydrolysis causes conformational change
  release of Na to ECF
• 2 K bind cause release of Pi to cytosol
• Conformational change 2 K released in cytosol

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Secondary Active Transport

• Energy stored in Na or H concentration gradient
  drives other substances against own gradients
• Indirect use of ATP
• Digitalis slows Na/Ca2 ion antiporters
• allows more Ca2 to stay inside heart muscle
  cells
• increases force of contraction ? strengthens
  heartbeat

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Transport in Vesicles

• Invaginations of PM enclose substances
  transport into or out of cell
• Endocytosis bringing something into cell
• Exocytosis release of something from cell
• Vesicular transport is an active process

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Vesicular Transport--Endocytosis

• Receptor-mediated endocytosis selective uptake
  of large molecules/particles by cells
• Ex internalization of LDL particles
• Phagocytosis macrophages neutrophils engulf
  large particles
• Particle binds to receptor protein on PM is
  surrounded by pseudopods
• Disposal of microbes, old cells, etc.
• Pinocytosis (bulk-phase endocytosis) cell
  drinking
• No receptor proteins

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Vesicular Transport--Exocytosis

• Exocytosis
• Vesicle formation inside cell
• Vesicle fuses w/ cell membrane
• Vesicle products released from cell
• digestive enzymes, hormones, NT, wastes
• Replace/recycle cell membrane lost during
  endocytosis

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CYTOPLASM

• Cytosol the semifluid portion of cytoplasm that
  contains inclusions and dissolved solutes
• Organelles specialized structures that perform
  specific functions in cellular growth,
  maintenance, and repro.

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The Cytoskeleton

• Network of protein filaments throughout cytoplasm
  
• Functions
• Structural framework of cell
• Cell/organelle movement
• Microfilaments
• Intermediate filaments
• Microtubules

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Centrosomes

• Contain centrioles paired cylinders arranged at
  right angles to one another
• Organize microtubules in interphase cells
• Organize mitotic spindle during cell division

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Cilia and Flagella

• Hair-like structures important for cellular
  movement
• Cilia
• numerous, short, projections extending from cell
  surface
• move materials across surface of cell
• Flagella
• much longer than cilia
• usually move an entire cell

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Cilia and Flagella

• Structure
• pairs of microtubules(92 array)
• covered by cell membrane
• basal body
• anchors to PM
• responsible for initiatingassembly
• Differences
• cilia
• short and multiple
• flagella
• longer and single

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Movement of Cilia and Flagella

• Cilia
• stiff during power stroke but flexible during
  recovery
• many coordinated together
• airways uterine tube
• Flagella
• single flagella wiggles in a wavelike pattern
• propels sperm forward

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Ribosomes

• Composed of ribosomal RNA protein
• Sites of protein synthesis
• Free ribosomes are loose in cytosol
• synthesize proteins found inside the cell
• Membrane-bound ribosomes
• attached to endoplasmic reticulum or nuclear
  membrane
• synthesize proteins needed for plasma membrane or
  for export
• Inside mitochondria, ribosomes synthesize
  mitochondrial proteins

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Ribosomal Subunits

• Large small subunits
• made in the nucleolus
• assembled in cytoplasm

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Endoplasmic Reticulum (ER)

• Network of membranes that form flattened sacs
• Store, package transport newly synthesized
  molecules
• Detoxification (SER in liver)
• Releases Ca2 ions in muscle contraction
  (sarcoplasmic reticulum)
• Fatty acid steroid synthesis (liver SER)

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Endoplasmic Reticulum

• Rough ER (RER)
• Extension of nuclear membrane
• Ribosomes on outer surface
• Secretory, membrane organelle proteins
• Smooth ER (SER)
• Extension of rough ER
• No ribosomes
• Detox, FA/steroid synth., Ca release in muscle

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Golgi Complex

• Flattened membranous sacs that process, sort, and
  deliver proteins lipids to other parts of cell
• Different enzymes allow for modification/packaging
  of various proteins

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Lysosomes

• Membrane-enclosed vesicles formed from Golgi
• Numerous digestive enzymes
• Functions
• digest foreign substances
• autophagy
• recycles own organelles
• autolysis
• tissue damage after death
• Tay-Sachs disease
• caused by absence of single lysosomal enzyme
• glycolipids accumulate interfere w/ nerve
  function

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Peroxisomes

• Similar in structure to, but smaller than
  lysosomes
• Contain oxygen-requiring enzymes
• Oxidases ? oxidize various organic compounds
• Catalases ? break down H2O2
• Important in normal catabolism of amino acids and
  fatty acids
• Oxidize toxic substances
• Alcohols
• Formaldehyde

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Proteosomes

• Destroy unneeded, damaged, or faulty proteins
• Proteases cut proteins into small peptides
• Faulty proteosomes are possible factor in some
  degenerative diseases
• Fail to break down abnormal proteins
• Parkinsons Alzheimers

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Mitochondria

• Cellular powerhouses
• Site of ATP production
• Catabolism of nutrients
• O2 required ? aerobic
• Located where O2 enters cell or ATP is used
• Bound by double membrane
• Cristae
• Folds in inner membrane
• Enormous surface area for reactions of cellular
  respiration
• Matrix
• Central cavity
• Site of metabolic reactions

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NUCLEUS

• Directs cellular activity
• Controls cell structure
• Most body cells have one nucleus (mononucleate)
• RBCs are anucleate
• Skeletal muscle fibers are multinucleate
• Parts of nucleus include
• nuclear envelope which is perforated by nuclear
  pores
• nucleolus
• genetic material (DNA)
• Contains cells hereditary units (genes) which
  are arranged on chromosomes

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NUCLEUS

• 46 (23 pair) human chromosomes
• Genes found on chromosomes
• Genes direct synthesis of specific protein
• Non-dividing cells contain nuclear chromatin
• Loosely packed DNA, RNA protein complex
• Histones proteins that direct DNA folding
• Dividing cells contain chromosomes
• Tightly packed DNA
• DNA copied itself before condensing into
  chromatids

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Chromosomes

• Each chromosome long molecule of DNA coiled
  together with several proteins
• Human somatic cells have 46 chromosomes (23
  pairs)
• Various levels of DNA packing represented by
  nucleosomes, chromatin fibers, loops, chromatids,
  chromosomes

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PROTEIN SYNTHESIS

• Genes expressed as proteins
• Proteins determine phys/chem characteristics of
  cells
• DNA is template for protein synthesis
• Transcription (txp)
• Genetic info in DNA copied onto single-stranded
  RNA
• Three types of RNA
• Messenger RNA (mRNA)
• Ribosomal RNA (rRNA)
• Transfer RNA (tRNA)
• Translation
• mRNA read by ribosomes
• Message translated into a. a. sequence of
  protein

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Transcription

• DNA sense strand template for creation of mRNA
  strand
• RNA polymerase (RNApol) attaches to promoter
  sequence initiates txp
• RNApol reaches terminator sequence detaches ?
  txp stops
• Genes contain XS information
• Pre-mRNA contains introns that are cut out by
  enzymes
• Exons regions of mRNA code for segments of
  protein
• gene splicing
• snRNPs
• Thus 1 gene can yield several proteins

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Protein Synthesis

• Instructions for making specific proteins found
  in DNA (your genes)
• transcribe that information ontomRNA molecule
• each sequence of 3 nucleotides in DNA base
  triplet
• each triplet transcribed as 3 RNA nucleotides
  (codon)
• translate message into sequence of amino acids
  in order to build protein
• each codon must be matched by anticodon found on
  the tRNA carrying a specific amino acid

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Translation

• Sequence of nucleotides (ntd) on mRNA is read
  by rRNA to construct a protein
• Small ribosomal subunit is attachment site for
  mRNA
• Large ribosomal subunit has 2 tRNA binding sites
• P site where tRNA-a.a. attaches to mRNA
• A site holds incoming tRNA-a.a.
• Specific tRNA molecules carry specific amino
  acids
• 3-nucleotide sequences codons
• AUG is ALWAYS the start codon
• tRNA anticodon UAC it codes for methionine
• Anticodons on tRNA match specific codons on mRNA
  so proper a.a can be strung together to create
  protein

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Translation

• Sequence is as follows
• Initiator tRNA
• Start codon on mRNA
• Functional ribosome formed
• initiator tRNA fits into P site on rRNA
• Anticodon of tRNA match codons of mRNA
• Stop codon on mRNA

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The sequence of translation

• Specific amino acids attach to molecules of tRNA.
  Another portion of the tRNA has a triplet of
  nitrogenous bases called an anticodon, a codon is
  a segment of three bases of mRNA.

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The sequence of translation

• Transfer RNA delivers a specific amino acid to
  the codon the ribosome moves along an mRNA
  strand as amino acids are joined to form a
  growing polypeptide.

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CELL DIVISION

• Process by which cells reproduce themselves
• nuclear division (mitosis and meiosis)
• cytoplasmic division (cytokinesis)
• Somatic cell division reproduction of any body
  cell except sex cells
• nuclear division (mitosis)
• cytokinesis
• distribute two sets of chromosomesone set into
  each of two separate nuclei
• Reproductive cell division production of gametes
  
• nuclear division (meiosis)
• cytokinesis

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Chromosome Number

• Human somatic cells contain 46 chromosomes (23
  pairs)
• Homologous chromosomes (homologs) two
  chromosomes that make up a chromosome pair
• A cell with a full set of chromosomes is diploid
  (2N)
• A cell with only one chromosome from each pair is
  haploid (N)
• Mitosis yields diploid cells
• Meiosis yields haploid cells

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Cell Cycle in Somatic Cells

• Orderly sequence of events by which cell
  duplicates its contents and divides in two
• Consists of interphase and mitotic phase (Figure
  3.28)

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Interphase

• Cell carries on every life process except
  division
• Doubling of DNA and centrosome
• Three subphases of interphase
• G1 replication of cytosolic components (G0 if
  non-dividing cell)
• S replication of chromosomes
• commitment stage ?cell will divide
• G2 cytoplasmic growth

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Replication of Chromosomes During Interphase

• Doubling of genetic material during interphase
  (S phase)
• DNA molecules unzip (histones)
• Mirror copy formed along each old strand
• Nitrogenous bases pair with complementary base
• 2 complete, identical DNA molecules formed

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Interphase

• Cell shows distinct nucleus
• DNA present as chromatin
• Nuclear membrane in tact

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MITOSIS Prophase

• Chromatin condenses shortens into chromosomes
• Identical chromatids joined by centromere
• Centrosomes migrate to opposite poles
• Disintegration of nuclear membrane/nucleolus

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Prophase

• Chromatin condenses into visible chromosomes
• pair of identical chromatids held together by a
  centromere
• Nucleolus nuclear envelope disappear
• Each centrosome moves to opposite ends of cell
• forms a mitotic spindle w/ 3 types of
  microtubules
• those that bind to kinetochore protein on
  centromere
• those that radiate outward
• those that extend between the 2 centrosomes
• spindle responsible for separation of chromatids
  to each new daughter cell

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MITOSIS Metaphase

• Centromeres line up at exact center of mitotic
  spindle, (metaphase plate or equator)

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MITOSIS Anaphase

• Splitting separation of centromeres
• Chromatids from each pair move toward opposite
  poles of cell
• appear V-shaped as they are pulled by centromeres
• Late anaphase formation of cleavage furrow
  begins

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MITOSIS Telophase

• Begins when chromatid movement stops
• Chromosomes at opposite poles revert to chromatin
  form
• New nuclear envelope/nucleoli form
• Mitotic spindle breaks up

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CYTOPLASMIC DIVISION Cytokinesis

• Division of parent cells cytoplasm and
  organelles
• Begins late anaphase/ early telophase
• Following completion of cytokinesis, interphase
  begins
• Cancer uncontrolled cell division ? some
  anticancer drugs stop this by inhibiting spindle
  formation

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Control of Cell Destiny

• Three possible destinies of a cell
• Live function without dividing
• Growth division
• Death
• CDKs crucial for regulation of cell
  growth/division
• Regulated by cyclins
• Apoptosis programmed cell death
• Triggered intra- or extracellularly by
  cell-suicide gene
• Removes unneeded/unwanted cells
• Necrosis pathological (abnormal) cell death
• Stimulates inflammatory response
• Tumor-suppressor genes normally inhibit cell
  division
• Ex p53 arrests cells in G1 ? damage leads to
  breast or colon cancers

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Reproductive Cell Division Meiosis

• Results in production of haploid (n) cells
  containing only 23 chromosomes
• Occurs in two successive stages
• Meiosis I
• Meiosis II

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Meiosis I

• Consists of four phases prophase I, metaphase I,
  anaphase I, and telophase I

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Prophase I

• Synapsis chromosomes become arranged in
  homologous pairs
• Resulting four chromatids form tetrad
• Tetrads may exchange genetic material between
  non-sister chromatids through crossing over.

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Metaphase I

• Homologous pairs of chromosomes line up along
  metaphase plate of cell, with homologous
  chromosomes side by side

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Anaphase I

• Members of each homologous pair separate, with
  one member of each pair moving to an opposite
  pole of cell.
• Telophase I and cytokinesis similar to telophase
  and cytokinesis of mitosis.
• The net effect of meiosis I is that each
  resulting cell contains only one member of each
  pair of homologous chromosomes. It is now
  haploid in number

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Meiosis II

• Prophase II, metaphase II, anaphase II, and
  telophase II
• Similar to those in mitosis, but result in four
  haploid (n) cells

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Review

• Figure 3.32 compares the processes of mitosis and
  meiosis

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CELLULAR DIVERSITY

• Not all cells look alike, nor do they perform
  identical functional roles in the body.
• Considerable variation
• 100 trillion cells in the body -- 200 different
  types
• Vary in size and shape related to their function
  (Figure 3.35).

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CELLS AND AGING

• Aging normal, progressive alteration of bodys
  homeostatic adaptive responses
• Physiological signs of aging
• Gradual deterioration in function
• Decline in responsiveness
• Net decrease in number of cells in body
  increased dysfunction of remaining cells
• Extracellular components of tissues (e.g.,
  collagen fibers and elastin) also change with age
• Theories of aging
• genetically programmed cessation of cell
  division, glc addition to proteins, free radical
  rxn, excessive immune responses

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DISORDERS HOMEOSTATIC IMBALANCES

• Cancer group of diseases characterized by
  uncontrolled cell proliferation
• Cells that divide without control develop into a
  tumor or neoplasm.
• Cancerous neoplasm malignant tumor or
  malignancy
• Capable of metastasizing
• spread of cancerous cells to other parts of the
  body
• A benign tumor noncancerous growth

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Cancer Uncontrolled cell division

• Hyperplasia increased number of cell divisions
• benign tumor does not metastasize (spread)
• malignant tumors spread because detach from tumor
  enter blood/lymph
• Causes
• exposure to carcinogens, x-rays, viruses
• every cell has genes that regulate growth
  development
• mutations in those genes due to radiation or
  chemical agents causes excess production of
  growth factors
• Carcinogenesis
• multistep process that takes years (and requires
  many different mutations) to occur

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Types of Cancer

• Carcinomas arise from epithelial cells.
• Melanomas cancerous growths of melanocytes
• Sarcomas arise from muscle cells or connective
  tissues.
• Leukemia cancer of blood-forming organs
• Lymphoma cancer of lymphatic tissue
• Growth and Spread of Cancer
• Cancer cells divide rapidly and continuously.
• Trigger angiogenesis
• Metastasis occurs when cancer cells leave site of
  origin travel to other tissues/organs

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Causes of Cancer

• Normal counterparts of oncogenes
  proto-oncogenes
• found in every cell
• cells fcn normally until a malignant ? occurs
• Anti-oncogenes or tumor-suppressing genes
• may produce proteins that normally oppose the
  action of an oncogene or inhibit cell division
• Carcinogenesis multistep process involving
  mutation of oncogenes anti-oncogenes
• 10 distinct mutations may have to accumulate in a
  cell before it becomes cancerous

77
Treatment of Cancer

• Difficult because it is not a single disease
  because all cells in a tumor do not behave in
  same way
• Various treatments include
• Surgery
• Chemotherapy
• Radiation therapy