Lecture ce4

Human Anatomy and Physiology, 7eby Elaine Marieb & Katja Hoehn

Copyright © 2007 Pearson Education, Inc.,publishing as Benjamin Cummings.

Lecture 3

Cells: The Living Units

THE CELL THEORY

• A cell is the basic structural and functional unit of all organisms

• According to the principle of complementarity of structure and function, the biochemical reactions occurring in a cell are dictated by the subcellular structures present in the cell

• Reproduction has a cellular basis



Figure 3.1: Cell diversity, p. 65.- different shapes and sizes

Fibroblasts

Erythrocytes

Epithelial cells

Macrophage

Nerve cell

Fat cell

Sperm

Skeletalmusclecell

Smoothmuscle cells

(a) Cells that connect body parts, form linings, or transport gases

(c) Cell that stores nutrients

(b) Cells that move organs and body parts

(d) Cell that fights disease

(e) Cell that gathers information and controls body functions

(f) Cell of reproduction

3 MAIN PARTS OF A CELL

• Plasma membrane – defines the boundary of a cell

• Cytoplasm – the interior of the cell between the plasma membrane and the nucleus; contains the cytoplasmic organelles

• Nucleus – contains the genes which control activities of the cell



Figure 3.2: Structure of the generalized cell, p. 66.

Secretion being releasedfrom cell by exocytosis

Peroxisome

Ribosomes

Roughendoplasmicreticulum

NucleusNuclear envelopeChromatin

Golgi apparatus

Nucleolus

Smooth endoplasmicreticulum

Cytosol

Lysosome

Mitochondrion

Centrioles

Centrosomematrix

Microtubule

Microvilli

Microfilament

Intermediate filaments

Plasmamembrane



Figure 3.3: Structure of the plasma membrane according to the fluid mosaic model, p. 67.

Bimolecularlipid layercontainingproteins

Polar heads ofphospholipidmolecules

Nonpolar tailsof phospholipidmolecules

Filaments ofcytoskeleton

Cytoplasm(watery environment)

Glycoprotein

Cholesterol

Outward-facinglayer ofphospholipids

Inward-facinglayer ofphospholipids

Extracellular fluid(watery environment)

Glycolipid

Peripheralprotein

Integralproteins

Carbohydrateof glycocalyx

The Plasma Membrane• Forms the boundary of a cell

• Thickness = 7-10nm; very thin

• Composed of 2 layers of phospholipids ( lipid bilayer) arranged tail to tail with the polar hydrophilic heads exposed to the aqueous extracellular fluid and the intracellular fluid

• Embedded in this lipid bilayer are Membrane Proteins, Cholesterol

• Lipid bilayer exhibits fluidity and the membrane proteins are in constant flux - their shapes constantly change as in a kaleidoscope or a mosaic pattern. Hence, the plasma membrane is said to be of the FLUID MOSAIC MODEL

• Cholesterol inserts between the phospholipids tails to stabilize the plasma membrane = “ cholesterol therefore maintains the integrity of the plasma membrane

The Membrane Proteins

• Integral Proteins: span the plasma membrane exposed on one surface or both surfaces of the plasma membrane.

Integral proteins exposed on both surfaces of the plasma membrane are called Transmembrane Proteins

• Peripheral Proteins: attached to integral proteins or the phospholipids’ heads on the cytoplasmic face of the plasma membrane



Figure 3.4: Some functions of membrane proteins, p. 68.

Transport(a) A protein that spans the membranemay provide a hydrophilic channelacross the membrane that is selectivefor a particular solute. (b) Sometransport proteins hydrolyze ATP as anenergy source to actively pumpsubstances across the membrane.

Enzymatic activityA protein built into the membrane maybe an enzyme with its active siteexposed to substances in the adjacentsolution. In some cases, severalenzymes in a membrane act as a teamthat catalyzes sequential steps of ametabolic pathway as indicated(right to left) here.

Receptors for signal transductionA membrane protein exposed to theoutside of the cell may have a bindingsite with a specific shape that fits theshape of a chemical messenger, suchas a hormone. The external signalmay cause a conformational changein the protein that initiates a chain ofchemical reactions in the cell.

Intercellular joiningMembrane proteins of adjacent cellsmay be hooked together in variouskinds of intercellular junctions.Some membrane proteins (CAMs)of this group provide temporarybinding sites that guide cellmigration and other cell-to-cellinteractions.

Cell-cell recognitionSome glycoproteins (proteinsbonded to short chains of sugars)serve as identification tags thatare specifically recognized byother cells.

Attachment to the cytoskeletonand extracellular matrix (ECM)Elements of the cytoskeleton (cell’s internal supports) and theextracellular matrix (ECM) may beanchored to membrane proteins,which help maintain cell shapeand fix the location of certainmembrane proteins. Others play arole in cell movement or bindadjacent cells together.

(a) (b)

ATP



Figure 3.5: Cell junctions, p. 70.

Linkerproteins

Plaque

Intermediate filament

Intercellular space

Intercellular space

Interlockingjunctional proteins

Microvilli

Tight junction

Plasma membranesof adjacent cells

Gap junction

Underlying basement membrane

Extracellular space between cells

Desmosome

Intercellularspace

Channelbetween cells(connexon)

(b) Desmosome

(a) Tight junction

(c) Gap junction

Membrane Junctions• Tight Junction – fusion of integral proteins in

plasma membrane of adjacent cells forming an “impermeable junction”

• Desmosome – linker proteins extending from plaques on the cytoplasmic surface of the plasma membrane of adjacent cells interdigitate to hold the cells together and prevent their separation; also known as “anchoring junction”

• Gap Junction – formed by hollow cylinder called connexons; it allows for the rapid transfer of ions

between cells; also known as “communicating junction”

MEMBRANE TRANSPORT – the plasma membrane is a selective barrier

1. Passive processes – substances cross the plasma membrane without any energy input

2 main types: Diffusion and Filtration Diffusion – 3 subtypes: Simple diffusion Facilitated diffusion

Osmosis 2. Active processes – the cell provides energy required to move

substances across the plasma membrane 2 main types: Active transport ( = “solute pumping”) and Vesicular

transport Vesicular transport – Exocytosis and Endocytosis Exocytosis – movement of substances out of the cell Endocytosis – movement of substances into the cell Phagocytois Pinocytosis Receptor-mediated endocytosis



Figure 3.7: Diffusion through the plasma membrane, p. 72.

Extracellular fluid

Cytoplasm

Lipid-solublesolutes

Lipidbilayer

Lipid-insolublesolutes

Watermolecules

Small lipid-insolublesolutes

(a) Simple diffusion directly through the phospholipid bilayer

(c) Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge

(b) Carrier-mediated facilitated diffusion via protein carrier specific for one chemical; binding of substrate causes shape change in transport protein

(d) Osmosis, diffusion through a specific channel protein (aquaporin) or through the lipid bilayer

DIFFUSION• Movement of substances from area of higher

concentration to area of lower concentration; substances move down their concentration gradient

• Simple diffusion – nonpolar/hydrophobic/lipid-soluble substances diffuse through the plasma membrane. Ex. Oxygen, carbon dioxide

• Facilitated diffusion – transport of large/polar substances mediated by carrier proteins embedded in the plasma membrane. Facilitated diffusion exhibits saturation, specificity

• Osmosis – movement of water from area of lower solute concentration to area of higher solute concentration through a semi-permeable membrane

Water moves through specific channels called aquaporins



Figure 3.8: Influence of membrane permeability on diffusion and osmosis, p. 73.

Leftcompartment:Solutionwith lowerosmolarity

Membrane

Solutemolecules(sugar)

Rightcompartment:Solutionwith greaterosmolarity

Both solutions havethe same osmolarity:volume unchanged

H2O

Solute

Leftcompartment

Membrane

Rightcompartment

Both solutions have identicalosmolarity, but volume of thesolution on the right is greaterbecause only water isfree to move

H2O

(a) Membrane permeable to both solute molecules and water

(b) Membrane impermeable to solute molecules, permeable to water

Tonicity• Movement of water in and out of cells can change the

shape or tone of cells.• Isotonic solution – concentration of solution inside and

outside of the cells is the same; the same amount of water moves in/out of the cells/ shape of cells remain unchanged

• Hypertonic solution – cells placed in solution with a higher concentration than solution inside cells; water moves via osmosis from the cells; cell crenate ( shrink)

• Hypotonic solution – cells are placed in a solution with a lower concentration than solution inside cells;

water moves via osmosis into the cells – cells swell and eventually burst

Filtration

• A passive process – no energy input

• Movement of solution from area of higher pressure to area of lower pressure; down a pressure gradient

Active Processes• Energy (ATP) is required for the movement of

substances across the plasma membrane• 2 types:Active transport and Vesicular transport• Active transport – movement of solutes/ions from area

of lower solute concentration to area of higher solute concentration (against a concentration gradient); mediated by carrier proteins. Active transport exhibits saturation and specificity.

Ex. sodium./potassium pump ( Na+/K+ pump)

Hence, active transport is also known as “Solute Pumping”



Figure 3.10: Operation of the sodium-potassium pump, an antiport pump (Na+–K+ ATPase), p. 76.

Cytoplasm

Extracellular fluid

K+ is released and Na+ sites are ready to bind Na+ again; the cycle repeats.

Cell ADP

Phosphorylation causes the protein to change its shape.

Concentration

The shape change expels Na+ to the outside, and extracellular K+ binds.

Loss of phosphate restores the original conformation of the pump protein. K+ binding triggers

release of the phosphate group.

Binding of cytoplasmic Na+ to the pump proteinstimulates phosphorylation by ATP.Na+

Na+

Na+

K+

K+

Na+Na+

K+K+

K+

K+

Na+

Na+

Na+

ATPP

P

Na+

Na+Na+

K+

K+

P

Pi

1

2

3

4

5

6

Active Process – Vesicular Transport• 2 types – Exocytosis and Endocytosis

• Exocytosis – movement of substances enclosed in vesicles from the interior of cells to the exterior.

Hormones, enzymes are secreted via exocytosis

• Endocytosis – movement of substances from the exterior of cells to the interior



Figure 3.12: Exocytosis, p. 78.

Extracellularfluid

Cytoplasm

Molecules tobe secreted

VesicleSNARE

Plasma membraneSNARE

Secretory vesicle

(a)

(b)

Movement of substances from the interior of the cell to its exterior



Figure 3.13: Clathrin-mediated endocytosis, p. 79.

Recycling ofmembrane andreceptors (if present)to plasma membrane

CytoplasmExtracellular fluid

Extracellularfluid

Plasmamembrane

Detachmentof clathrin-coatedvesicle

Clathrin-coatedvesicle

Uncoating

Uncoatedvesicle

Uncoatedvesiclefusing withendosome

To lysosomefor digestionand releaseof contents

Transcytosis

Endosome

Exocytosisof vesiclecontents

Clathrin-coatedpit

Plasmamembrane

Ingestedsubstance

Clathrinprotein

(a) Clathrin-mediated endocytosis

Endocytosis - Movement of substances from the exterior of the cell to its interior

Endocytosis• Movement of substances from the exterior of a cell into the cell’s

interior. 3 types:

i) Phagocytosis – movement of solid particles from the exterior into the cell; solid particles are enclosed in vesicles called PHAGOSOMES; Lysosomes fuse with the phagosomes to digest the phagosomes and its contents. Cells that perform phagocytosis are called Phagocytes.

ii) Pinocytosis – movement of solution into cells by enclosing the solution in vesicles

iii) Receptor-mediated endocytosis – substances bind to specific receptors on the surface of the cell; clathrin appear where the substances are bound; coated pits form to transport substances into the cell.

Receptor-mediated endocytosis exhibits saturation and specificity



Figure 3.13: Clathrin-mediated endocytosis, p. 79.

Recycling ofmembrane andreceptors (if present)to plasma membrane

CytoplasmExtracellular fluid

Extracellularfluid

Plasmamembrane

Detachmentof clathrin-coatedvesicle

Clathrin-coatedvesicle

Uncoating

Uncoatedvesicle

Uncoatedvesiclefusing withendosome

To lysosomefor digestionand releaseof contents

Transcytosis

Endosome

Exocytosisof vesiclecontents

Clathrin-coatedpit

Plasmamembrane

Ingestedsubstance

Clathrinprotein

(c) Receptor-mediated endocytosis

Extracellularfluid

Cytoplasm

Bacteriumor otherparticle

Pseudopod

Clathrinprotein

(b) Phagocytosis

Clathrinprotein

Membranereceptor

(a) Clathrin-mediated endocytosis

1

3

2

c) Pinocytosis – movement of solution into cells

Transcytosis and Vesicular trafficking

Trancytosis: Movements of substances enclosed in caveolae into a cell, across the cell and released on the opposite side of the cell via exocytosis

Vesicular Trafficking: Intracellular movement of substances in coatmer- coated vesicles from organelle to organelle with the cell



Figure 3.15: The role of K+ in generating the resting membrane potential, p. 82.

Potassiumleakagechannel

Protein anionCytoplasm

K+ diffuse down their steepconcentration gradient (outof the cell) via leakagechannels. Loss of K+ resultsin a negative charge on theinner plasma membraneface.

A negative membrane potentialis established when the movementof K+ out of the cell equals K+

movement into the cell.

K+ also move into the cellbecause they are attractedto the negative chargeestablished on the innerplasma membrane face.

+

–

–

– –– –

––

+

+ + +

++

+

Na+

Na+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

A–

A–K+

K+

K+

Cl–

Cl–

1 2

The Resting Membrane Potential (RMP)

• RMP of resting cells is between -50mV to -100mV

• RMP is established by the partial/selective permeability of the plasma membrane to potassium ion (K+) diffusion over sodium ion( Na+) diffusion.

• K+ concentration is higher inside the cell than outside the cell – K+ diffuses out of the cell down its electrochemical gradient

• Na+ concentration is higher outside of the cell than inside the cell – Na+ diffuses into the cell down its electrochemical gradient

• The plasma membrane is about 75 times more permeable to K+ than Na+ = more K+ diffuses out of cell than Na+ diffusing into the cell = more positive ions move out of the cell making the cytoplasmic surface of the plasma membrane negative compared to the extracellular surface

Abraham Alam

since there are lots of positive ions on the inside, the cytoplasmic phase of the cell membrane has this negative ions inside... think about it.K+ goes out, but Na+ also comes in

THE CYTOPLASM• Composed of cytosol, cytoplasmic organelles, and

inclusions ( such as glycosomes, melanosomes)• Cytosol – the viscous, semitransparent fluid• Cytoplasmic organelles- specialized subcellular

compartments with specific functions i) Mitochondria = “power plants”

ii) Ribosomes = sites of protein synthesis iii) Endoplasmic reticulum ( ER) Rough ER = “membrane factories” Smooth ER = lipid/drug metabolism

iv) Golgi apparatus = “traffic director” of the cell v) Lysosomes = “demolition crew” vi) Peroxisomes = neutralize harmful free radicals vii) Cytoskeleton

Abraham Alam

organelles suspended in cytosol

2 Types of cytoplasmic organelles• Membranous cytoplasmic organelles:

Mitochondria

Endoplasmic Reticulum (ER)

Golgi apparatus

Lysosomes

Peroxisomes

• Nonmembranous cytoplasmic organelles: Ribosomes

Cytoskeleton



Figure 3.17: Mitochondrion, p. 85.

Enzymes

Matrix

Cristae

MitochondrialDNA

Ribosome

Outermitochondrial membrane

Innermitochondrialmembrane

(a) (b)

Mitochondria • Threadlike membranous organelles - constantly

changing their shapes• Contain own DNA and are self-replicating organelles

• Composed of 2 membranes enclosing a fluid matrix

• 2 mitochondrial membranes are – outer and inner membranes

• The inner membrane consists of infoldings called cristae

• Resident enzymes of the cristae and the matrix breakdown food in the presence of oxygen

( = aerobic respiration) to release energy hence, mitochondria are referred to as the “POWER PLANTS” of a cell

Abraham Alam

also produce proteins

Abraham Alam

without oxygen, you don't make as many ATP by glycolysis

RibosomesEach ribosome is composed of 2 globular subunits – small ribosomal subunit and a large ribosomal subunitEach ribosomal subunit consists of protein and rRNA

2 types of ribosomes – Free and Bound

Free ribosomes float freely in the cytosol and synthesize proteins that stay in the cell

Bound ribosomes – bound to the surface of rough ER and synthesize proteins that are transported to the plasma membrane or for export out of the cell ( secreted)

Abraham Alam

small one is not rRNA and big one is NOT protein... they come together to form a functioning ribosome



Figure 3.18: The endoplasmic reticulum (ER) and-

ribosomes, p. 86.

Nuclear envelope

RibosomesRough ER

Smooth ER

Smooth ER Rough ER with boundribosomes

Large subunit

Small subunit

Functionalribosome

+

(a)

(b) (c)

Endoplasmic Reticulum - ER• Composed of meandering membranous channels

enclosing fluid-filled cavities called cisternae • 2 Types of ER – Rough ER and Smooth ER

• Rough ER – external surface is studded with ribosomes ( Bound ribosomes) – these ribosomes synthesize the plasma protein and secretory proteins. Rough ER is therefore abundant in secretory cells such as liver cells

• Rough ER is referred to as the “Membrane factory” because the synthesis of integral proteins (by ribosomes) and phospholipids in plasma membranes is associated with the rough ER



Figure 3.19: The signal mechanism targets ribosomes to the ER for protein synthesis, p. 87.

Cytosol

Ribosomes

mRNA

Coatomer-coatedtransportvesicle

Transportvesiclebudding off

Releasedglycoprotein

ERcisterna

ERmembrane

Signal-recognitionparticle(SRP)

Signalsequence

Receptorsite

Sugargroup

SignalsequenceremovedGrowing

polypeptide

1

2

34

5

Smooth ER

Smooth ER

Smooth ER is devoid of ribosomes = “smooth surface”Its membrane-bound enzymes catalyze: - Synthesis of fats , cholesterol and steroid hormones - Fat absorption, transport and metabolism- Glycogenolysis which results in energy production - Detoxification of drugs and carcinogens in liver and kidney cells

Abraham Alam

duties of smooth ER: fat synthesis, fat absorption, metabolism,exam - ask which cytoplasmic organelle is abundant in cholesterol synthesis for example

Abraham Alam

break down stored glycogen into glucose for energy



Figure 3.20: Golgi apparatus, p. 88.

Cis face—“receiving” side ofGolgi apparatus

Transport vesiclefrom the Golgi

Transport vesiclefrom the Golgi

Secretory vesiclefrom trans face

Trans face—“shipping” side ofGolgi apparatus

New vesiclesforming

New vesicles forming

Cisternae

Transport vesiclefrom rough ER

Golgi apparatus

(a)

(b)

Golgi Apparatus• Composed of stacked /flattened membranous sacs• Receives proteins and lipids from the rough ER • Golgi modifies, packages and tags proteins and lipids to

their specific destinations hence, the Golgi apparatus is referred to as the “Traffic director” of the cell

• 3 types vesicles produced by the Golgi:

- secretory vesicles which contain proteins released via exocytosis

- Vesicles that contain integral proteins and lipids destined for the plasma membrane to incorporated into the plasma membrane

- Vesicles containing powerful digestive enzymes that remain in the cell = LYSOSOMES to digest phagosomes… more on next slides



Figure 3.21: The sequence of events from protein synthesis on the rough ER to the final distribution of those proteins, p. 88.

Secretion by exocytosisExtracellular fluid

Plasma membrane

Vesicle incorporatedinto plasma membrane

Coatomercoat

Lysosomes containing acidhydrolase enzymes

PhagosomeProteins in cisterna

Membrane

Vesicle

Pathway 3

Pathway 2

Secretory vesicles

Proteins

Pathway 1

Golgi apparatus

CisternaRough ER



Lysosomes -

Golgiapparatus

Lysosome

Rough ER

Tra

Nucleus

Spherical membranous organelles - contain powerful digestive enzymes that digest vesicles and biological molecules.

Function: - Digest phagosomes hence, lysosomes are abundant in phagocytes - Digest worn-out organelles - Stimulate glycogenolysis - Involved in bone resorption to release calcium

Hence, lysosomes are referred to as a cell’s “demolition crew”

Peroxisomes

Peroxisome

Membranous sacs that contain Powerful enzymes that neutralize harmful free radicals 2 kinds of enzymes in peroxisomes: Oxidases and Catalases

Free radicals (harmful) + Oxidases -- Hydrogen peroxide ( harmful) Hydrogen peroxide + Catalase - Water

Abraham Alam

abundant in detoxification and free radical cells

Cytoskeleton• “Cell skeleton” – consists of non membranous rod-like structures

that support other cytoplasmic organelles and allow for movements• 3 Types based on size and function:

i) Microtubules – largest diameter = 25nm wide

ii) Intermediate filaments – diameter between that of a microtubule and a microfilament = 10nm

iii) Microfilaments – smallest diameter = 7nm



Figure 3.24c: Cytoskeleton, p. 91.

Tubulin subunits

25 nm

( Microtubule

Microtubules• Largest cytoskeleton – hollow tubes composed of the globular

proteins called TUBULINS

• Radiate from the CENTROSOME which acts as a microtubule organizing center

• Function of Microtubules:

• Serve as “tracks” to transport intracellular substances

- cytoplasmic organelles and secretory vesicles attached by motor molecules to microtubules for intracellular, vesicular trafficking



Figure 3.25: Interaction of motor molecules (motor proteins) with cytoskeleton elements, p. 92.

Receptor formotor molecule

Microtubuleof cytoskeleton

Motor molecule(ATP powered)

Organelle

Cytoskeletal elements(microtubules or microfilaments)

Motormolecule(ATPpowered)

(a) (b)

ATPATP



Figure 3.26: Centrioles, p. 92.

Centrosome matrix

Centrioles

Microtubules

(a)

(b)

(c)

Cilia and flagella• Centrosome ( microtubule-organizing center) contains a pair of

CENTRIOLES at right angles to each other.

• Centrioles sprout spindle fibers ( mitotic spindles) required for cell division

• Centrioles form 2 types of cell extensions:

CILIA and FLAGELLUM• Cilia – cellular extensions that occur in large numbers on

the apical ( exposed ) surface of cells• Several cells in the body are ciliated • Cilia beat to create a current that moves substances

across the surface of the cells• Flagellum – a single, longer cellular extension• Flagellum beats to propel the cell it extends from • The only flagellated cell in the human body is sperm



Figure 3.27: Cilia structure and function, p. 93.

Power stroke

Layer of mucusCell surface

Recovery stroke

Basalbody(centriole)

Plasmamembrane

Outerdoubletmicrotubules

Centralmicrotubules

Centralmicrotubules

Dyneinarms

Outerdoubletmicrotubules

Plasmamembrane

Cilium 1 2 3 54 6 7

(b) Ciliary motion

(c) Movement of mucus across cell surfaces

(a) Cilium

Sperm – Flagellated cell

•

•

= flagellum



Figure 3.24a-b: Cytoskeleton, p. 91.

Actin subunit

7 nm

Fibrous subunits

10 nm

Microfilament

(Intermediate filament

Intermediate Filaments• Composed of tough, insoluble fibrous fibers

• Most stable type of cytoskeleton

• Provide tensile strength to cells by resisting pulling forces placed on the cells

• Given specific names in specific cell types:

Tonofilaments in epidermal cells

Neurofilaments in neurons

Microfilaments• Have the smallest diameter• Composed of the protein ACTIN• The arrangement of microfilaments is unique to each

cell• Function:

Involved in changes in cell shape or cell motility as in contraction

Involved in the formation of cleavage furrow during cytokinesis

Involved in the changes of the plasma membrane during endocytosis and exocytosis



Figure 3.28: The nucleus, p. 96.

Condensed chromatin

Nuclear envelope

Nucleus

NucleolusPores

(a)

Cisternae of rough ER

The Nucleus• Control center of a cell

• A cell with one nucleus = Uninucleate

• A cell with many nuclei = Multinucleate

• A cell without a nucleus = Anucleate

• 3 main regions:

• Nuclear membrane

• Nucleolus

• Chromatin



Figure 3.28: The nucleus, p. 96.

Condensedchromatin

Nuclear envelope

Nucleus

Surface of nuclear envelope.TEM prepared by freeze-fracture. A, inner membrane; B, outer membrane; NP, nuclear pore (pore complex); White arrows, fracture lines of outer membrane.

Pore complexes (TEM). Eachpore is ringed by protein particles.

Nuclear lamina (TEM). Thenetlike lamina composed of intermediate filaments called lamins lines the inner surface of the nuclear envelope.

Nucleolus

Pores

Cisternae ofrough ER

(a)

(b)

Nuclear Envelope • = Nuclear Membrane

• Double-layered selective membrane with nuclear pores

• Nuclear pores allow molecules to enter /exit the nucleus – proteins translocate from the cytoplasm into the nucleus; RNA molecules move from the nucleus into the cytoplasm

The Nucleolus

Nucleolus

Dark spherical nonmembranous structure in the nucleus

Synthesizes ribosomal RNA ( rRNA) required for assembling the 2 ribosomal subunits – small and large Ribosomes are sites for protein synthesis hence,nucleoli are prominent in cells producing large amounts of proteins



Figure 3.29: Chromatin and chromosome structure, p. 98.

Metaphasechromosome

Supercoiledstructure(200-nm diameter)

Tight helical fiber(30-nm diameter)

Chromatid(700-nm diameter)

Nucleosome(10-nm diameter)

Linker DNA

Chromatid(“beads ona string” )structure

Histones

DNAdoublehelix(2-nmdiameter)

(a)

(b)

1

2

3

5

4

Chromatin• Composed of DNA and the

histone proteins

• Consists of structural units called NUCLEOSOMES

• Each nucleosome is composed of 8 globular histone proteins connected by the thread-like DNA

• DNA consists of structural units called NUCLEOTIDES

DNA

Histone proteins

Nucleic AcidsStructural units of nucleic acids are NUCLEOTIDES

Each nucleotide is composed of – i) pentose sugar - deoxyribose or Ribose ii) Nitrogen-containing base - A,G, C, T, U iii) Phosphate group

2 Types of Nucleic Acids: Deoxyribonucleic Acids = DNARibonucleic Acids = RNA

Compare DNA and RNA



Figure 3.30: The cell cycle, p. 99.

G1

Growth

SGrowth and DNA

synthesisG2

Growth and finalpreparations for

divisionM

G2 checkpoint

G1 checkpoint Interphase

Cytokinesis

MitosisTelo

ph

ase

An

aph

aseM

etaphase

Prophase

Mitotic phase (M)

The Cell Cycle• The series of events a cell undergoes from the time it’s

formed until it reproduces

• Consists of 2 major sequential periods:

i) Interphase – protein synthesis, cell growth and DNA replication occur

Consists of 3 sequential phases: G1, S, G2

ii) Cell division – mitosis and cytokinesis occur

Mitosis – Nuclear division: 4 sequential phases:

Prophase, Metaphase, Anaphase, Telophase

Cytokenesis – Cytoplasmic division



Leadingstrand

Replicationfork

DNApolymerase III

DNA polymerase III

Laggingstrand

Key: = Adenine= Thymine= Cytosine= Guanine

New strandforming

Old(template)strand

Old (template) strand

Newlymadestrand

DNA of onechromatid

Figure 3.31b: Replication of DNA, p. 100.

SEMI-CONSERVATIVE

REPLICATION:Each daughter DNA Consists of a an old strand and a newly-Synthesized strand



Figure 3.31a: Replication of DNA, p. 100.

PrimaseReplisome

DNA template

RNA primer

RNA primer

RNA primerbeing replacedby DNAnucleotides

Completeddaughter strand

DNApolymerase III

DNApolymerase I

Newly made DNA

Replicase

(a)



Figure 3.32: The stages of mitosis, p. 102.

Interphase Early prophase Late prophase

Centrioles(two pairs)

Nucleolus

Nuclearenvelope

Plasmamembrane

Condensedchromatin

Early mitoticspindle

Pair ofcentrioles

CentromereChromosome, consistingof two sister chromatids

Aster

Fragments ofnuclearenvelope

Kinetochoremicrotubule

Spindlepole

Kinetochore

Polarmicrotubules



Figure 3.32: The stages of mitosis (continued), p. 103.

Metaphaseplate Nucleolus

forming

Nuclearenvelopeforming

Contractilering atcleavagefurrow

SpindleDaughterchromosomes

MetaphaseAnaphase Telophase and cytokinesis

Mitosis

• Describe the 4 stages of mitosis

• Compare and contrast Prophase and Telophase

Cancer cells

• Neoplasm – abnormal excessive proliferation of cells.• 2 classes of neoplasm – Benign and Malignant• Benign neoplasm – grows slowly and it’s confined to

one location• Malignant neoplasm = CANCER – grows fast and

aggressively; metastasizes to other organs

• Based on your understanding of the cell cycle, discuss ways you may design cancer therapeutic drugs



Figure 3.33: Simplified scheme of information flow from the DNA gene to protein structure, p. 105.

Nuclearenvelope

DNA

Pre-mRNA

mRNA

Ribosome

Polypeptide

Translation

RNA Processing

Transcription



Figure 3.34a: An overview of transcription, p. 106.Codingstrand

Templatestrand

PromoterTermination signal

Transcription unitIn a process mediated by a transcriptionfactor, RNA polymerase binds topromoter and unwinds 16–18 basepairs of the DNA template strand

RNApolymerase

Unwound DNA

RNAnucleotides

RNA polymerasebound to promoter

mRNA synthesis begins

RNA polymerase moves down DNA;mRNA elongates

RNAnucleotides

mRNA synthesis is terminatedRNApolymerase

mRNA

DNA

mRNA transcript(a)



Figure 3.34b: An overview of transcription, p. 106.

RNAnucleotides

RNA polymerase

Unwindingof DNA

Coding strand

Rewinding of DNA

mRNARNA-DNAhybrid region

Template strand

(b)



Figure 3.35: The genetic code, p. 107.SECOND BASE

UUG

UUA

UUC

UUUPhe

Leu

CUG

CUA

CUC

CUU

Leu

AUA

AUC

AUU

Ile

GUG

GUA

GUC

GUU

Val

UCG

UCA

UCC

UCU

Ser

CCG

CCA

CCC

CCU

Pro

ACG

ACA

ACC

ACU

Thr

GCG

GCA

GCC

GCU

Ala

UAC

UAUTyr

CAG

CAA

CAC

CAUHis

Gln

AAG

AAA

AAC

AAUAsn

Lys

GAG

GAA

GAC

GAUAsp

Glu

UGC

UGUCys

Trp

CGG

CGA

CGC

CGU

Arg

AGG

AGA

AGC

AGUSer

Arg

GGG

GGA

GGC

GGU

Gly

UAA Stop UGA Stop

AUGMet orStart

UAG Stop UGG

U C A G

G

A

C

U

G

A

C

U

G

A

C

U

G

A

C

U

U

C

A

G

TH

IRD

BA

SE

FIR

ST

BA

SE

The Genetic Code – indicates how the base sequence of a gene is translated into amino acids



Figure 3.36: Translation, p. 108.

After mRNA processing, mRNA leaves nucleus and attaches to ribosome, and translation begins.

Amino acids

tRNA

Aminoacyl-tRNAsynthetase

tRNA "head" bearinganticodon

Largeribosomalsubunit

Small ribosomalsubunit

Released mRNA

mRNA

Template strandof DNA

RNA polymeraseNuclear poreNuclear membrane

Portion of mRNAalready translated

Direction ofribosomeadvance

Nucleus

Once its amino acid is released, tRNA is ratcheted to the E site and then released to reenter the cytoplasmic pool, ready to be recharged with a new amino acid.

Incoming aminoacyl-tRNA hydrogen bonds via its anticodon to complementary mRNA sequence (codon) at the A site on the ribosome.

Energized by ATP, the correct amino acid is attached to each species of tRNA by aminoacyl-tRNA synthetase enzyme.

As the ribosome moves along the mRNA, a new amino acid is added to the growing protein chain and the tRNA in the A site is translocated to the P site

Codon16

Codon15

Codon17

PCG

GCC C AUU AUG

E A

Ile

Ala

Phe

SerGlyMet

Ile

AAGU AU

U AU

1

4

3

2



Figure 3.37: Polyribosomes, p. 109.

Ribosome

Completedpolypeptide

Peptide chain

Ribosomalunits

mRNA

mRNARibosome

1

1

1

1

1

1

2

2

2

2

3

3

3

4

45

(a) (b)



Figure 3.38: Information transfer from DNA to RNA, p. 110.

DNAmolecule

Gene 1

Gene 3

Gene 5

DNA base sequence (triplets)of the gene coding for thesynthesis of a particularpolypeptide chain

Base sequence (codons) ofthe transcribed mRNA

Consecutive base sequencesof tRNA anticodons capableof recognizing the mRNAcodons calling for theamino acids they transport

Amino acid sequence of thepolypeptide chain

1 2 3 4 5 6 7 8 9

Codons

Triplets

tRNA

1 2 3 4 5 6 7 8 9

StartStop;

detach

Met Pro Ser Leu Lys Gly Arg Phe

Lecture ce4

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Transcript of Lecture ce4