Plasma Membrane
· Barrier for cell
· Facilitates and restricts cellular exchange of substances
· Maintains electrochemical gradient and receptors for signal transduction |
· Lipid bilayer consisting of phospholipids, cholesterol and proteins |
Nucleus
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· Contains genetic code |
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· Controls cell division and functions |
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· Composed of DNA and proteins |
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Three components: The chromatin, the nuclear envelope, and the nucleoli
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· Largest organelle |
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· Site of DNA replication and transcription |
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· Has an affinity for basic dyes (deep purple with wright stain) |
Nucleolus
· Synthesizes ribosomal RNA and assembles ribosome subunits |
· Composed of ribosomal RNA |
Ribosomes
· Synthesizes proteins |
· Composed of protein and ribosomal RNA |
Rough Endoplasmic Reticulum
· Synthesizes most membrane-bound proteins |
· Studded with ribosomes
· Membrane-lined tubules that branch and connect to nuclear membrane |
Smooth Endoplasmic Reticulum
· Synthesizes phospholipids and steroids
· Detoxifies drugs; stores calcium |
· No ribosomes
· Membrane-lined tubules adjacent/touching with RER |
Membrane Carbohydrates
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In the outer layer, carbohydrates (oligosaccharides) are covalently linked to some membrane proteins: Carbohydrates + protein = glycoproteins
Carbohydrates + phospholipids = glycolipids
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Glycoprotein + glycolipid = glycocalyx Glycocalyx provide a negative surface charge
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Glycoprotein and glycolipid are surface markers or antigens |
Phospholipid Asymmetry in the Membrane
Phosphatidylserine + Phosphatidylethanolamine = inner layer
Sphingomyelin + Phosphatidylcholine = outer layer
Nucleus: Nuclear Envelope
Have nuclear pore = passage of molecules between the nucleus and the cytoplasm |
Nucleus: Nucleoli
· Site of ribosomal RNA (rRNA) production
· Nucleolus produce ribosome>ribosome create protein># of nucleoli = protein synthesis that occurs
· Mature cells = decreased protein synthesis
Golgi Apparatus
· Stack of flattened sacs called cisternae
· Modify, sort, and pack macromolecules for secretion or delivery to other organelles
· Vesicles that contains membrane-bound and soluble proteins from RER > enter golgi (cis face) > modified by enzymes either for glycosylation, sulfation, or phosphorylation > exit golgi (trans face) > lysosomes/secretory vesicles are formed > go to plasma membrane
Cytoplasm
· tRNA carry and transport amino acid to the ribosome
· mRNA provides the genetic code for the sequence of amino acids for the protein being synthesized
· Cells that produce proteins = increased ribosome = dark blue stain (basophilia)
· Therefore, RBC precursor produce hb (a protein)>more basophilic>darker
Hematopoiesis
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Bone marrow 3rd trimester to adulthood
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Stromal cells · Protects BM
· Secrete many different growth factors required for stem cell, progenitor cell, and precursor cell survival
· Creates an extracellular matrix = By secreting collagen, fibronectin, thrombospondin, laminin, and proteoglycans (such as hyaluronate, chondroitin sulfate, and heparan sulfate)
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Growth factors (ligands) · Regulate the proliferation and differentiation of progenitor and precursor cells
· Bind to a receptor>signals nucleus>activate kinase>promote response (proliferate/differentiate)
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Tumor Suppressor Genes
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Code proteins that ensure and control cell division only when required |
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Loss of function of tumor suppressor gene = uncontrolled cell division = cancer |
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TP53 - Most important Tumor suppressor gene · Detects G1 DNA damage
· Trigger apoptosis
· Ensures only DNA-error free cells can undergo division
· TP53 > Inc TP21 > inhibits cyclin/cdk complex > no cell division occurs
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Regulation of the Cell Cycle
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Needed to prevent abnormal or mutated cells from going through the cell cycle and producing an abnormal clone |
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FOUR MAJOR CHECKPOINTS IN THE CELL CYCLE · G1 restriction point - checks for the appropriate amount of nutrients and appropriate cell volume
· G1 DNA damage checkpoint - checks the DNA for damage and makes the cell wait for DNA repair or initiates apoptosis.
· G2 DNA damage checkpoint - verify that replication took place without error or damage (defects=mitosis is blocked)
· Mitosis metaphase - checks the alignment of chromosomes and the integrity of the spindle apparatus. (defects=anaphase is blocked)
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Mitosis
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Prophase · Chromosomes condense
· Duplicated centrosomes begin to separate
· Mitotic spindle fibers appear
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Prometaphase · Nuclear envelope disassembles
· Centrosomes move to opposite poles
· Sister chromatids attach to the mitotic spindle fibers
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Metaphase · Sister chromatids align
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Anaphase · Sister chromatids separate and move on opposite poles
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Telophase · Mitotic spindle fibers disappear
· Nuclear membrane reassembles
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Cytokinesis · Cell divides into two identical daughter cells
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Mitochondria
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· Produces most of the cell’s ATP via oxidative phosphorylation |
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Capable of self-replication An organelle that has its own DNA and RNA
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Cristae - oxidative enzymes are attached |
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Mitochondrial enzymes: · oxidize pyruvate and fatty acids to acetyl CoA
· citric acid cycle oxidizes the acetyl CoA producing electrons for the electron transport pathway
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Lysosomes
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· Contains hydrolytic enzymes that degrade unwanted material in the cell |
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Lysosomal enzymes · Low pH cytosol (acidic) = active
· High pH (bcontain hydrolytic enzymes (intracellular digestive process)
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Lysosomal lipid storage diseases · Gaucher disease
· Tay-Sachs disease
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Microfilaments
· Supports cytoskeleton and motility |
· Double-stranded, intertwined solid structures of actin |
Microfilaments and Intermediate Filaments
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· Supports cytoskeleton and motility |
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· Double-stranded, intertwined solid structures of actin |
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Actin microfilaments · 5 to 7 nm in diameter
· associate with myosin to enable cell motility, contraction, and intracellular transport.
· near the nuclear envelope to assist in cell division
· near the plasma membrane to provide cytoskeletal support
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Intermediate filaments · 8 to 10 nm diameter
· most durable element of the cytoskeleton
· provide structural stability for the cells
· Found in keratins and lamins
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Microtubules
· Maintains cell shape, motility, and mitotic process
· Form the mitotic spindle fibers during mitosis and are the major components of centrioles.
· Hollow cylinder of α and β tubulin forming 13 protofilaments
Centrosome
· Contains centrioles that serve as insertion points for mitotic spindle fibers
· Two cylinder-shaped centrioles at right angle; nine bundles of three microtubules.
Cell Membrane
Polar-charged hydrophilic (water-soluble) structures |
Phospholipid’s phosphate end + cholesterol’s hydroxyl radical |
Non-polar-charged hydrophobic (water-insoluble) structures |
Phospholipid’s fatty acid chains + cholesterol’s steroid nucleus |
Membrane Proteins
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1. Transmembrane proteins · Channels and transporters for water, ions, and other molecules between the cytoplasm and the external environment.
· Also function as receptors and adhesion molecules.
· Have cytoplasmic ends to attach the cytoskeletal proteins = structural integrity to the cell
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2. Cytoskeletal proteins · Found only on the cytoplasmic side of the membrane
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Example: Hereditary spherocytosis
Inherited gene mutation that codes for transmembrane or cytoskeletal proteins > disrupt membrane integrity > short RBC life span > hemolytic anemia
Nucleus: Chromatin
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1. Heterochromatin · Condensed clumping pattern
· Transcriptionally inactive
· Seen in mature cells = they are less transcriptionally active
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2. Euchromatin · Diffuse, uncondensed, open chromatin
· Genetically active
· Pale blue when stained with wright stain
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CELL CYCLE
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Purpose · Replicate DNA
· Distribute identical chromosome copies equally to two daughter cells during mitosis
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Biochemical and morphologic four-stage process · G1 (gap 1), S (DNA synthesis), G2 (gap 2), and M (mitosis)
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CELL CYCLE
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G0 (quiescence) · Cell is not actively in the cell cycle.
· Resting period until cell have right requirements to divide
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G1 · Period of cell growth; synthesis of components necessary for replication
· Lasts about 10 hours
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S stage · DNA replication takes place
· 8 hours
· Produces sister chromatids
· Centrosome is also duplicated
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G2 · The tetraploid DNA is checked for proper replication and damage
· 4 hours
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M stage · Division of chromosomes and cytoplasm into two daughter cells.
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Cyclin/CDK complexes
1. Cyclin (protein) binds to CDK (enzymes)
2. Cyclin-CDK complex activate the proteins required in progression of cell cycle
Via phosphorylation (Phosphate group attach to target proteins)
·G1 – cyclin D + cdk4 and cdk6
·G1 going to S phase – cyclin E + cdk2
·S phase to G2 – cyclin e (decrease) Cyclin A (increase) + cdk2 and cdk1
·Mitosis – Cyclin B + cdk1
NECROSIS AND APOPTOSIS
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Necrosis - direct external injury to cells · Cell swell
· Nucleus lyse
· Membrane no integrity
· Pathologic – cell injury
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Apoptosis - self-inflicted cell death from the cell itself · Cell shrink
· Nucleus condenses
· Membrane intact
· Physiologic – remove unwanted/unneeded cell
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