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Lecture 3b.

Anatomy of the cell – organelles, cell division, and the central

dogma

Anatomy of the Cell

Organelles

Question

A red blood cell is placed in a solution and a few minutes later, the cell shrinks (crenates). What was the tonicity of the solution?

Question

Celery begins to wilt after it has been in the fridge for a while. You can actually restore some of its crispness by submersing it in a solution. What kind of solution would you use?

Cellular level

Cytology: structure and function of cellsCell biology

Cell Theory

Cells are smallest unit of lifeAll cells come from previously existing cells through cell divisionCells perform all physiological functionsMaintains homeostasis at the level of the cell which impacts tissues, organs, and systems

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Numbers and diversityBody contains trillions of cellsAlso has thousands of different types of cells (there are hundreds of different types of neurons alone)

Two general classes of cells

1. Somatic cells (diploid, 2n) – two copies of each chromosome

2. Sex cells (haploid, n) – one copy of each chromosome

Organelles

Internal cell structures that perform specific cellular functionsCytoplasmic organelles:

MembranousMitochondria, peroxisomes, lysosomes, endoplasmic reticulum, and Golgi apparatus

NonmembranousCytoskeleton, centrioles, and ribosomes

Exterior: Plasma membrane

Cytoplasm

Cytoplasm – material between plasma membrane and the nucleusCytosol – largely water with dissolved protein, salts, sugars, and other solutes

Cytoplasm = cytosol + organelles

Anatomy of a Cell

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Nonmembranous: Cytoskeleton

The “skeleton” of the cellDynamic, elaborate series of protein rods running through the cytosolConsists of:

MicrofilamentsIntermediate filamentsMicrotubules

Muscle cells contain thick filaments

MicrofilamentsThe smallest in diameter (7nm), most fragileMade of the protein actin and located in the periphery of the cellAttached to the cytoplasmic side of the plasma membrane

Braces and strengthens the cell surfaceInvolved in cell movement and shape changes

Intermediate filamentsIntermediate in size (7-11nm)Tough, insoluble protein fibers with high tensile strengthThe most durable of the cytoskeletal fibersSeveral varieties exist (e.g. keratin)Functions

Provides shape of the cellResist pulling forces

Thick filaments

Only found in muscle cellsMade of protein myosinInteract with actin microfilaments to cause contraction

MicrotubulesLargest of the fibers (25nm)Dynamic, hollow tubes made of the spherical protein tubulinMicrotubular array of the cell is near the nucleusFunctions:

Determine the overall shape of the cell and distribution of organellesHelp move structures in the cell (like highways)Form the spindle apparatusForm centrioles and cilia

Microtubules

Figure 3.24c

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Centrioles and Cilia are made of microtubules

CentriolesOrganize mitotic spindle during mitosisForm the bases of cilia and flagella

CiliaUsed to propel material in one direction across cell surfacesWhip-like, motile cellular extensions on exposed surfaces of certain cellsMove substances

Motor Molecules

Protein complexes that function in motilityPowered by ATPAttach to receptors on organelles

Cilia

Figure 3.27b

Cilia

Figure 3.27c

Ribosomes are the organelles for protein synthesis

Consists of two subunits made of rRNA and protein Site of protein synthesisTwo kinds of ribosomesfound in cells

Free ribosomessynthesize soluble proteinsFixed ribosomessynthesize proteins to be incorporated into membranes

Membranous organelles

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Endoplasmic ReticulumInterconnected network of tubes and parallel membranes enclosing cisternaeContinuous with the nuclear membraneFour major functions

Synthesis StorageTransportDetoxification

Two types of ERSmooth ERRough ER

Rough ER

“Rough” because xternal surface studded with fixed ribosomesSynthesizes secreted and integral membrane proteins and may chemically modify themResponsible for the synthesis of phospholipids for cell membranesAlso important for shipment of proteins to the Golgi apparatus

Endoplasmic Reticulum (ER)

Figure 3.18a, c

Smooth ER

Why is it called smooth?Responsible for the synthesis and storage of lipids and carbohydratesDetoxification of drugs and toxins

Very large and developed in liver cells. Why?

Stucture function

Smooth ERCatalyzes the following reactions in various organs of the body

In the liver – lipid and cholesterol metabolism, breakdown of glycogen and, along with the kidneys, detoxification of drugs In the testes – synthesis of steroid-based hormones In the intestinal cells – absorption, synthesis, and transport of fatsIn skeletal and cardiac muscle – storage and release of calcium

Golgi ApparatusTypically contains 5-6 Stacked and flattened membranous sacs called cisternaeFunctions in modification, concentration, and packaging of proteins:

Modifies and packages secreted proteinsPackages special enzymes

Also renews the cell membrane (adds lipids)

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Golgi ApparatusTransport vessels from the ER fuse with the cis face of the Golgi apparatusProteins then pass through the Golgi apparatus to the trans faceSecretory vesicles leave the trans face of the Golgi stack and move to designated parts of the cell

Figure 3.20a

Pathways of the Golgi Apparatus

Figure 3.21

Secretion by exocytosisExtracellular fluid

Plasma membrane

Vesicle incorporatedinto plasma membrane

Coatomercoat

Lysosomes containing acidhydrolase enzymes

PhagosomeProteins in cisterna

Membrane

Vesicle

Pathway 3

Pathway 2Secretory vesicles

Proteins

Pathway 1

Golgiapparatus

Cisterna Rough ER

LysosomesSpherical membranous bags containing digestive enzymesArise by budding off of GolgiDigest ingested bacteria, viruses, and toxinsDegrades and recyles nonfunctional organellesSpecializations:

Breakdown glycogen and release thyroid hormonesSecretory lysosomes are found in white blood cells, immune cells, and melanocytes

Like a “disposal” for large objects from inside and outside the cell

Lysosome Functions

Endomembrane System

System of organelles that function to: Produce, store, and export biological moleculesDegrade potentially harmful substances

System includes:Nuclear envelope, smooth and rough ER, lysosomes, vesicles, Golgi apparatus, and the plasma membrane

Endomembrane System

Figure 3.23

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Lysosomal storage diseases

Tay-Sachs Lack an enzyme (protein) called hexosaminidase A (hex A) necessary for breaking down certain fatty substances in brain cells called gangliosides (see AM p.29)

PeroxisomesMembranous sacs containing enzymes that detoxify harmful or toxic substances (which cells have a lot?)Breaks down fatty acids and some organic compoundsProduced by the division of existing peroxisomesConvert free radicals to hydrogen peroxide (H2O2)Catalase enzyme coverts H2O2 to H2O and O2

Like a smaller-scale recycler for molecule-sized things within the cell (cf. lysosome).

Mitochondria“Powerhouse” of the cell…makes most of the cell’s ATP via aerobic cellular respirationDouble membrane structure with shelf-like cristae

Nucleus - structureConsists of a double membraneContains nuclear envelope, nucleoli, and chromatinHolds the DNA in the form of chromosomesAlso has RNA and enzymesHas pores for entry/exit

Nucleus - Functions

Functions as the gene-containing control center of the cell Contains the genetic library with blueprints for nearly all cellular proteinsRegulates gene expression: dictates the kinds and amounts of proteins to be synthesized

Nucleus - ContentsNuclear Envelope

Selectively permeable double membrane barrier containing poresOuter membrane is continuous with the rough ER and is studded with ribosomesInner membrane is lined with the nuclear lamina, which maintains the shape of the nucleusPores regulates transport of large molecules into and out of the nucleus

NucleolusDark-staining spherical body (or bodies) within the nucleusSite of ribosome production

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Nucleus –Chromatin

Threadlike strands of DNA and histonesArranged in fundamental units called nucleosomesForm condensed, barlike bodies of chromosomes when the nucleus starts to divide

Figure 3.29

SUMMARY

Diversity of human cellsStructures and functions of membranous and nonmembranous organelles

Anatomy of the Cell

Cell Life Cycle - Mitosis

Figure 3.30

Cell Cycle

InterphaseGrowth (G1), synthesis (S), growth (G2)

Mitotic phaseMitosis and cytokinesis

Cell Cycle

Most of a cell’s life is spent in a nondividingstate (interphase)

Cell is preparing to divide or performing its normal cell functions

During interphase the DNA, is referred to as chromatin

InterphaseG0 : cells that cease dividing (often permanently)

perform specialized cell functions only G1 (gap 1): metabolic activity and vigorous growth

organelle duplication, protein synthesis S (synthesis): DNA replicationG2 (gap 2) : final preparation for division

finishes protein synthesis and centrioles replicate

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G0Cells that are no longer dividing are said to be

in G0.

Q: What cells can you think of that are in G0?

ChromosomesHumans have 23 pairs; one of each pair comes from Mom, the other comes from DadThe two chromosomes of each pair are called homologous chromosomesEach Chromosome is a long molecule of DNA.Each contains thousands of genes arranged in a single file.Each gene is a segment of DNAEach gene represents blueprints for a protein

Cell Division - Mitosis

Necessary for growth and maintenance of organismsResponsible for humans developing from a single cell to 75 trillion cellsMitosis divides duplicated DNA into 2 identical sets of chromosomes:

DNA coils tightly into chromatidschromatids connect at a centromere

MitosisThe phases of mitosis are:

ProphaseMetaphaseAnaphaseTelophase

CytokinesisCleavage furrow formed in late anaphase by contractile ringCytoplasm is pinched into two parts just after mitosis ends

Mitosis - Overview Prophase

Chromatin condenses into chromosomesNucleoli disappearCentriole pairs separate and the mitotic spindle is formed

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Prophase

Figure 3.32.3

MetaphaseChromosomes with sister chromatidscluster at the middle of the cell with their centromeres aligned at the exact center, or equator, of the cell called the metaphase plate

AnaphaseCentromeres of the chromosomes splitMotor proteins in kinetochores pull one of each sister chromatidstoward polesAt this point, each chromatid is now called a chromosome

Telophase and Cytokinesis

New sets of chromosomes unwind into chromatinNew nuclear membrane is formed from the rough ERNucleoli reappearCytokinesis completes cell division

Cleavage furrow may be visable as early as late anaphase

Control of Cell Division

Surface-to-volume ratio of cells Chemical signals such as growth factors and hormonesContact inhibitionCyclins and cyclin-dependent kinases (Cdks) complexes

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Regulation of cell division

Mitotic Rate and Energyslower mitotic rate means longer cell lifecell division requires energy (ATP)

Muscle cells, neurons rarely divideExposed cells (skin and digestive tract) live only days or hours

Nucleus Controls Cell Structure and Function

Direct control through synthesis of: structural proteinssecretions (environmental response)

Indirect control over metabolism through enzymes

Anatomy of the Cell

Central Dogma

Topics – Central Dogma

DNA and DNA replicationProtein synthesis

RNATranscription (RNA synthesis)Translation (protein synthesis)

Deoxyribonucleic acid (DNA) -function

Contains genes which are functional units of heredityEach gene contains the instuctions for how to make one or more proteinsExists in the nucleus as chromatin, when cell prepares to divide the DNA is replicated and coiled to form a chromosome (two chromatids)Always found in the nucleus

DNA structure

The DNA molecule resembles a spiral ladder called a double Helix (It is double stranded)Contains alternating sugar/phosphate backbone attached by covalent bonds and Nitrogen containing bases (A, T, C, and G)Monomers of DNA are called nucleotides.Strands run anti-parallel and have orientation

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DNA bases

A-------TT-------AG-------CC-------G

Held together by hydrogen bondsComplementaritymeans given one strand, you can always predict the other

There are four different nitrogenous bases;

1. Adenine (A)2. Thymine (T)3. Cytosine (C)4. Guanine (G)

DNA bases are complementary:

KEY CONCEPT

The nucleus contains chromosomesChromosomes contain DNADNA stores genetic instructions for proteinsProteins determine cell structure and function

The Central Dogma

DNA RNA Protein

DNA Replication

1. Transcription

2. Translation

DNA ReplicationCopies ALL the DNA in a cell in order to distribute it into two daughter cells during cell divisionOccurs only during “S Phase” of mitosisRequires the enzyme DNA PolymeraseSplits the two original DNA strands and builds new complementary DNA strands to make two complete and identical sets of the genetic materialDNA NEVER LEAVES THE NUCLEUS

DNA Replication

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DNA Replication: ProductDNA Template DNA Complementary

A------------------------TT------------------------AG------------------------CC------------------------GA-------------------------TT-------------------------A

Protein Synthesis: from gene to protein

DNA serves as master blueprint for protein synthesisGenes are segments of DNA carrying instructions for a polypeptide chainTriplets of nucleotide bases form the genetic libraryEach triplet specifies coding for an amino acid

DNA instructions become proteins in two steps

1. Gene transcribed into mRNA2. mRNA translated into protein

Protein synthesis requires:several enzymesribosomes3 types of RNA

Ribonucleic acid (RNA)Unlike DNA:

Single stranded Bases are A, C, G, U (instead of T)Has ribose sugar instead of deoxyribose

Like DNAContains alternating sugar/phosphate backbone attached by covalent bonds

3 typesmRNA - messenger (translated into protein)rRNA - ribosomal (makes up most of ribosomes)tRNA - transfer (helps in translation from mRNA to protein)

2. TranscriptionThe process of making a single strand of RNA from the DNA code in a gene

In transcription a complementary RNA strand is made from the DNA template strandOnly a short portion of the DNA is “copied” into RNA – that portion is called a gene

Requires the enzyme RNA Polymerase to build the RNA strandFinished product called mRNA leaves the nucleus to be translated into protein in the cytoplasm

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Overview of Transcription

Transcription: Product

DNA RNA StrandA------------------UT------------------AG------------------CC------------------GA------------------UT------------------A

3. Translation

AKA: Protein Synthesis - the mRNA strand is “read” by the ribosomes and a strand of amino acids is made.Secreted and integral proteins are made on the rough ER, those that will stay in the cytoplasm are made on free ribosomes.the language of nucleic acids (mRNA) is “translated” into the language of amino acids (protein)

How is the language translated?

The Genetic Code RNA stores genetic information in sets of three nucleotides called codons. Each codon specifies a particular amino acid (3 nucleic acid bases = 1 amino acid)There are 64 codons and only 20 amino acidsAn adapter molecule allows mRNA codons to be read and the proper amino acids to be put into the growing protein

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The “genetic code” Overviewof Translation

amino acid

anticodon

codon

tRNA

TranslationmRNA moves into the cytoplasm through a nuclear pore and is bound by a ribosome (free or fixed)Adapter molecule tRNA delivers amino acids to ribosome

tRNA is like the translatorEach tRNA has an anticodon that matches and binds to the codon on the mRNA1 mRNA codon translates to 1 amino acidEnzymes in the ribosome join amino acids with peptide bondsResulting protein has specific sequence of amino acids (Why important?)

Figure 3–13

KEY CONCEPT

Genes: are functional units of DNA contain instructions for 1 or more proteins

Protein synthesis requires:several enzymesribosomes3 types of RNA

Genetic Code

There are 43 = 64 codons and only 20 amino acidsThis means there are more than one codonfor each amino acid. In other words, several codons specify for the same amino acid.

Question

Why does this redundancy exist in the genetic code?

What is the consequence of two different codons coding for the same amino acid?

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Mutations

Mutation is a change in the nucleotide sequence of a gene:

can change gene functionCauses:

exposure to chemicalsexposure to radiationmistakes during DNA replication

Mutations can lead to cancer

Mutations

Changes in the DNAMay or may not cause a change in the protein and/or a change in the function of that proteinCan be “silent” mutations

SUMMARY

Structures and functions of DNA, RNA, and chromosomesCentral Dogma: DNA replication, transcription, translation