The Cell Lecture Ch 1 (Dr. Dobson) TEST 1

Question 1

The Objective of continued Genomic Research include the following:

Answer 1

1) Find variations in the DNA sequence among people and determine their significance. The most common type of genetic
variation is known as a SINGLE NUCLEOTIDE POLYMORPHISM or SNP (pronounced “snip”). These small differences may
help PREDICT A PERSON’S RISK OF PARTICULAR DISEASES AND RESPONSE TO CERTAIN MEDICATIONS.

2) Discover the 3-dimensional structures of PROTEINS and identify their functions.
3) DEVELOP AND APPLY GENOME-BASED STRATEGIES FOR THE EARLY DETECTION, DIAGNOSIS, AND TREATMENT OF DISEASE!!!!!!
4) Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.
5) Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.
6) Continue to explore the ethical, legal, and social issues raised by genomic research.

Question 2

Human Genome

Answer 2

• 3.2 Bullion DNA Base PAIRS
• Within the Genome, 20,000 Protein Endowing Genes (1.5% of the Genome)!!!!!!!
• Proteins act as:
  a) Enzymes
  b) Structural Components
  c) Signaling Molecules
• Proteins used to assemble and maintain all cells of the Body

Question 3

The No-Protein- Coding Sequences (the other 98.5%)

Answer 3

1) Promoter and enhancer regions that provide binding sites for TRANSCRIPTION FACTORS
2) Binding sites for factors that ORGANIZE AND MAINTAIN higher order chromatin structures

3) NONCODING REGULATORY RNAs:
- More than 60% of the genome is transcribed into RNAs that are never translated into protein, but which nevertheless can regulate gene expression through a variety of mechanisms. The two best-studied varieties—MICRO-RNAs and LONG NONCODING RNAs—are described later!!!!!

4) Mobile genetic elements (e.g., TRANSPOSONS).
- More than one third of the human genome is composed of these elements “JUMPING GENES”.
- These segments can move around the genome, exhibiting wide variation in number and positioning even amongst closely related species (i.e., humans and other primates).
- They are IMPLICATED IN GENE REGULATION AND CHROMATIN ORGANIZATION, but their function is still not well established.

5) Special structural regions of DNA, in particular TELOMERES (chromosome ends) and centromeres (chromosome “tethers”)

Question 4

Polymorphisms

Answer 4

• Genetic Variation associated with Diseases are located in these Non-Portion Coding regions of the GENOME. These genetic Variations are referred to as POLYMORPHISMS

Question 5

Epigenetics

Answer 5

• Heritable changes in GENE EXPRESSION that are NOT CAUSED by ALTERATIONS in DNA Sequence

Question 6

Histones

Answer 6

NUCLEOSOMES:
- DNA Segments wrapped around LOW MOLECULAR WEIGHT Proteins called HISTONES!!!!

HISTONES can be MODIFIED BY:
a) Methylation 
b) Acetylation 
c) Phosphorylation
(EPIGENETIC ALTERATIONS)

• DNA can also be Methylated

**These MODIFICATIONS are REVERSIBLE!!!

Question 7

These events have a role in Development of Disease and Malignancy

Answer 7

1) Transcriptional activation
2) Transcriptional repression
3) Increased transcription
4) Open DNA for transcription or condense it to become Inactive
5) Transcriptional silencing

Question 8

Cellular Housekeeping

Answer 8

• Protection from Environment
• Nutrient Acquisition
• Communication
• Movement
• Renewal of Senescent Molecules
• Molecular Catabolism
• Energy Generation

Question 9

Proper Organization of Phospholipids

Answer 9

*** Proper Organization of Phospholipids is IMPORTANT for CELL HEALTH, as Specific Phospholipids INTERACT with Particular Membrane Proteins, Influencing their DISTRIBUTION and FUNCTION

• PHOSPHOTIDYLINOSITOL on the inner membrane leaflet can be phosphorylated, serving as an ELECTROSTATIC SCAFFOLD for intracellular proteins; alternatively, polyphosphoinositides can be hydrolyzed by phospholipase C to generate intracellular second signals like diacylglycerol and inositol triphosphate.
• PHOSPHOTIDYLSERINE is normally restricted to the inner face where it confers a negative charge involved in electrostatic protein interactions; however, when it flips to the extracellular face, which happens in cells undergoing APOPTOSIS (PROGRAMMED CELL DEATH), it becomes an “eat me” signal for phagocytes. In the special case of platelets, it serves as a cofactor in the clotting of blood.
• GLYCOLIPIDS and SPHINGOMYELIN are preferentially expressed on the extracellular face; glycolipids (and particularly Gangliosides, with complex sugar linkages and terminal sialic acids that confer negative charges) are important in cell-cell and cell- matrix interactions, including inflammatory cell recruitment and sperm-egg interactions

Question 10

Plasma Membrane Proteins

Answer 10

• The plasma membrane is liberally studded with a variety of PROTEINS AND GLYCOPROTEINS involved in (1) Ion and Metabolite Transport, (2) Fluid-Phase and Receptor-Mediated uptake of macromolecules, and (3) Cell-Ligand, cell-matrix, and cell-cell interactions.
• Many plasma membrane proteins function together as large complexes; these may either be aggregated under the control of Chaperone molecules in the RER or by lateral diffusion in the plasma membrane followed by complex Formation in situ.

Question 11

Examples of Plasma Membrane Proteins

Answer 11

1) AQUAPORINS:
• Aquaporins are special integral membrane proteins that allow renal tubular epithelium to Transport large Volumes of WATER
• Transported molecules require specific transporters i.e. Glucose
• Active transport against a gradient may require energy (ATP). This is how the multidrug resistance protein works

Question 12

Cytoskeleton and Cell to Cell Interactions

Answer 12

1) ACTIN Microfilaments
2) INTERMEDIATE Filaments
3) MICROTUBULES

Question 13

Actin Microfilaments

Answer 13

• Actin microfilaments are 5- to 9-nm diameter fibrils formed from the Globular Protein ACTIN (G-actin), the most abundant cytosolic protein in cells.
• The G-actin monomers noncovalently polymerize into LONG FILAMENTS (F-actin) that intertwine to form double-stranded helices with a defined polarity; new globular subunits are added (or lost) at the “positive” end of the strand.
• In MUSCLE CELLS, the filamentous protein Myosin binds to Actin, and moves along it, driven by ATP hydrolysis (the basis of muscle contraction).
• In Non-muscle cells, F-actin assembles via an assortment of actin-binding proteins into well-organized bundles and networks that control cell shape and movement.

Question 14

Intermediate Filaments

Answer 14

• Are 10-nm diameter fibrils that comprise a large and heterogeneous family. Individual types have characteristic tissue-specific patterns of expression that can be useful for assigning a cell of origin for poorly differentiated tumors.

A) LAMIN A, B, and C: Nuclear Lamina of all cells

B) VIMENTIN: Mesenchymal cells (fibroblasts, endothelium)

C) DESMIN: Muscle Cells, forming the scaffold on which actin and myosin contract

D) NEUROFILAMENTS: axons of neurons, imparting strength and rigidity

E) GLIAL FIBRILLARY ACIDIC PROTEIN: glial cells around neurons

F) CYTOKERATINS: at least 30 distinct varieties, subdivided into acidic (type I) and neutral/basic (type II); different types present in different cells, hence can be used as cell markers

Question 15

Microtubules

Answer 15

• Are 25-nm-thick fibrils composed of Noncovalently Polymerized dimers of α- and β-tubulin arrayed in constantly elongating or shrinking hollow tubes with a defined polarity; the ends are designated “+” or “−”.
• The “−” end is typically embedded in a microtubule organizing CENTER (MTOC or CENTROSOME) near the nucleus where it is associated with paired centrioles; the “+” end elongates or recedes in response to various stimuli by the addition or subtraction of tubulin dimers.
• WITHIN CELLS, MICROTUBULES CAN SERVE AS CONNECTING CABLES FOR “MOLECULAR MOTOR” PROTEINS THAT USE ATP TO MOVE VESICLES, ORGANELLES, OR OTHER MOLECULES AROUND CELLS ALONG MICROTUBULES

Question 16

Cells interact and communicate with one another by forming JUNCTIONS that provide mechanical links and enable surface receptors to recognize ligands on other cells.

Cell junctions are organized into three basic types:

Answer 16

1) Occluding Junctions (TIGHT JUNCTIONS)
- The complexes that mediate the cell-cell interactions are composed of multiple transmembrane proteins, including Occludin , Claudin, Zonulin, and Catenin

2) Anchoring Junctions (DESMOSOMES)
- In belt desmosomes, the transmembrane adhesion molecules are called E-CADHERINS and are associated with intracellular Actin Microfilaments, by which they can influence cell shape and/or motility.

3) Communicating Junctions (GAP JUNCTIONS) Gap junctions play a critical role in cell-cell communication; in CARDIAC
MYOCYTES, for example, cell-to-cell calcium fluxes through gap junctions allow the myocardium to behave like a functional SYNCYTIUM capable of coordinated waves of contraction—the beating of the heart.

Question 17

Biosynthetic Machinery

Answer 17

The Endoplasmic Reticulum (ER) is the site for synthesis of all the transmembrane proteins and lipids for plasma membrane and cellular organelles, including ER itself. It is also the INITIAL SITE for the Synthesis of all molecules destined for EXPORT OUT of the cell.

• Membrane-Bound Ribosomes on the cytosolic face of RER translate mRNA into proteins that are extruded into the ER lumen or become integrated into the ER membrane.
• Chaperone molecules RETAIN proteins in the ER until these modifications are complete and the proper conformation is achieved. IF A PROTEIN FAILS TO APPROPRIATELY FOLD OR OLIGOMERIZE, IT IS RETAINED AND DEGRADED WITHIN THE ER!!!

Question 18

Cystic Fibrosis

Answer 18

AFFECTED PROTEIN:
- Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

PATHOGENESIS:
- Loss of CFTR leads to DEFECTS in CHLORIDE Transport

Question 19

Familial Hypercholesterolemia

Answer 19

AFFECTED PROTEIN:
- LDL Receptor

PATHOGENESIS:
- Loss of LDL Receptor leading to Hypercholesterolemia

Question 20

Tay-Sachs Disease

Answer 20

AFFECTED PROTEIN:
- Hexosaminidase Beta Subunit

PATHOGENESIS:
- Lack of Lysosomal Enzyme leads to STORAGE of GM 2 GANGLIOSIDES in Neurons

Question 21

Alpha- 1- Antitrypsin Deficiency

Answer 21

AFFECTED PROTEIN:
- Alpha 1 - Antitrypsin

PATHOGENESIS:
- Storage of Nonfunctional Protein in HEPATOCYTES causes APOPTOSIS; Absence of Enzymatic Activity in Lungs causes DESTRUCTION of ELASTIC Tissue giving rise to EMPHYSEMA!!!!

Question 22

Creutzfeldt- Jacob Disease

Answer 22

AFFECTED PROTEIN:
- Prions

PATHOGENESIS:
- Abnormal folding of Pr Psc causes Neuronal Cell Death

Question 23

Alzheimer Disease

Answer 23

AFFECTED PROTEIN:
- A Beta Peptide

PATHOGENESIS:
- Abnormal Folding of A Beta Peptides causes Aggregation within Neuron and Apoptosis

Question 24

Smooth Endoplasmic Reticulum

Answer 24

• The SER in most cells is relatively sparse and primarily exists as the transition zone from RER to transport vesicles moving to the Golgi.
• However, in cells that SYNTHESIZE STERID HORMONES (e.g., in the gonads or adrenals), or that catabolize lipid- soluble molecules (e.g., in the liver), the SER may be particularly conspicuous.
• Indeed, repeated exposure to compounds that are metabolized by the SER (e.g., phenobarbital catabolism by the cytochrome P-450 system), can lead to a reactive SER HYPERPLASIA.
• The SER is also responsible for sequestering INTRACELLULAR CALCIUM; subsequent release from the SER into the cytosol can mediate a number of responses to extracellular signals (including apoptotic cell death).
• The Golgi apparatus consists of stacked CISTERNAE that progressively MODIFY (glycosylate) proteins in an orderly fashion.
• Some of this Glycosylation is important in directing molecules to Lysosomes (via the mannose-6-phosphate receptor, Chapter 5); other glycosylation adducts may be important for cell-cell or cell-matrix interactions, or for clearing senescent cells (e.g., platelets and red cells).
• In addition to the stepwise glycosylation of lipids and proteins, the CIS Golgi network can RECYCLE Proteins back to the ER; the TRANS Golgi network sorts proteins and lipids and dispatches them to other organelles (including the plasma membrane), or to secretory vesicles destined for extracellular release.
• The Golgi complex is especially prominent in cells specialized for SECRETION, including Goblet cells of the intestine, Bronchial epithelium (secreting large amounts of polysaccharide-rich mucus), and Plasma cells (secreting large quantities of antibodies).

Question 25

Waste Disposal

Answer 25

• Lysosome and Proteosomes

Question 26

Autophagy

Answer 26

• Autophay involves sequestration of Cellular Organelles into Cytoplasmis Autophagic Vacuoles (Autophagosomes) that fuse with Lysosomes and Digest the Enclosed Material
• Autophagy is an Adaptive Response that is ENHANCED during NUTRIENT DEPRIVATION!!!!!!!!!!!!!!!!!!!!!
• Autophagosome formation is Regulated by more than a dozen proteins that act in a coordinated and sequential Manner
• Dysregulation of Autophagy occurs in many disease states including cancers, Inflammatory Bowel Disease, and Neurodegenerative Disorders. Autophagy plays a role in HOST DEFENSE AGINST Certain Microbes

Question 27

Lysosomal Degredation and Proteasomal Degredation

Answer 27

Endocytosis:
- Pinocytosis or Receptors Mediated Endocytosis

Phagocytosis:
- Macrophages or Neutrophils

• Free Ubiquitin:
• Degrades Cytosolic Protein and Transcription factors. Identified by UBIQUITIN “Tag”

Question 28

Mitochondria and Cellular Metabolism

Answer 28

• Have their own DNA/genome
• Almost all DNA is MATERNALLY derived
• Provide machinery for ENERGY
• Fundamental ROLE in CELL DEATH!!!!!!!!

Description:
- PURE OXIDATIVE Phosphorylation produces abundant ATP, but also “BURNS” Glucose to CO2 and H2O, leaving Carbon Moieties suitable for use as BUILDING BLOCKS for Lipids or Proteins.

• For this reason, RAPIDLY GROWING Cells (Both Benign and Malignant) UPREGULATE Glucose and Glutamine Uptake and DECREASE their Production of ATP per Glucose Molecule, a phenomenon called the WARBURG EFFECT!!!!!!!!!!!!

Question 29

Mitochondria and Cellular Metabolism Cont

Answer 29

• In addition to providing ATP and Metabolites that enable the BULK of Cellular Activity, Mitochondria also regulate the BALANCE of CELL SURVIVAL AND DEATH!!!!
• Programmed Cell Death, a Central Feature of Normal Tissue Development ant Turnover:
  a) Cytotoxic T Cells
  b) Inflammatory Cytokines
  c) DNA Damage
  d) Intracellular Stress

*** Failure of Programmed Cell Death —–> MALIGNANCY!!!!!

** Premature Cell Death —-> NEURODEGENERATIVE DISEASE

Question 30

Cellular Activation

Answer 30

* Cell Communication is CRITICAL in Multicellular Organsisms**

• Loss of cellular communication and the “social controls” that maintain normal relationships of cells can variously lead to UNREGULATED GROWTH (cancer) or an Ineffective Response to an EXTRINSIC STRESS (as in shock)!!!!!!!

Question 31

Intracellular Receptors

Answer 31

INTRACELLULAR RECEPTORS are transcription factors that are activated by lipid-soluble ligands that can easily cross the plasma membrane.

• Examples of Cell-Permeable, hydrophobic ligands for this class of receptor include VITAMIN D and STEROID Hormones, which activate Nuclear Hormone Receptors. Uncommonly, the signaling ligand diffuses into adjacent cells; this is the case with NITRIC OXIDE, which directly activates the enzyme Guanylyl Cyclase to generate cyclic GMP, an intracellular second signal.

Question 32

Cell Surface Receptors

Answer 32

CELL-SURFACE RECEPTORS are generally transmembrane proteins with extracellular domains that bind soluble secreted ligands. Depending on the receptor, ligand binding can then:
(1) OPEN Ion Channels (typically at the synapse between electrically excitable cells)

(2) ACTIVATE an Associated GTP-binding Regulatory Protein (G protein)
(3) ACTIVATE an Endogenous or Associated Enzyme, often a TYROSINE KINASE

(4) TRIGGER a PROTEOLYTIC Event or a change in protein binding or stability that activates
a latent transcription factor.

SIGNALS TRANSDUCED BY CELL SURFACE RECEPTORS ARE OFTEN DERANGED IN DEVELOPMENT DISORDERS AND IN CANCERS!!!!!!***

Question 33

Signal Transduction Pathway

Answer 33

• Binding of a Ligand to a Cell Surface Receptor MEDIATES signaling by inducing clustering of the receptor (receptor cross-linking) or other types of physical perturbations ( Fig. 1-11 ).
• The common theme is that all of these perturbations cause a CHANGE in the PHYSICAL STATE of the intracellular domain of the receptor, which then triggers additional Biochemical Events that lead to SIGNAL TRANSDUCTION.
• CELLULAR RECEPTORS ARE GROUPED INTO SEVERAL TYPES BASED ON THE SIGNALING MECHANISMS THEY USE ADN THE INTRACELLULAR BIOCHEMICAL PATHWAYS THEY ACTIVATE ( Fig. 1-11 ).
• Receptor signaling typically leads to the formation or modification of biochemical intermediates and/or activation of enzymes, and ultimately to the generation of ACTIVE Transcription Factors that enter the nucleus and alter gene expression:

**** Categories of signaling receptors, including receptors that utilize a nonreceptor tyrosine kinase; a RECEPTOR TYROSINE KINASE; a nuclear receptor that binds its ligand and can then influence transcription; a seven-transmembrane receptor linked to heterotrimeric G proteins; NOTCH, which recognizes a ligand on a distinct cell and is CLEAVED Yielding an intracellular fragment that can enter the nucleus and influence transcription of specific target genes; and the WNT/FRIZZLED pathway where activation RELEASES INTRACELLULAR β-CATENIN from a protein complex that normally drives its Constitutive Degradation. The released β-catenin can then migrate to the nucleus and act as a TRANSCRIPTION FACTOR. Lrp5/Lrp6, Low- Density-Lipoprotein (LDL) receptor related proteins 5 and 6, are highly homologous and act as co-receptors in Wnt/Frizzled signaling.

Question 34

Matching Pathology with Receptor

Answer 34

1) NON RECEPTOR TYROSINE KINASE BASED RECEPTOR:
- Rous Sarcoma Visu

2) TYROSINE KINASE RECEPTOR:
- Insulin
- Epidermal Growth Factor
- PDGF

3) NUCLEAR HORMONE:
- Breast Cancer

4) NOTCH LIGAND:
- Dysregulated in Many Cancers

5) FRIZZLED/ WNT:
- Cancers, Inflammatory Disease, Neurologic Disorders

6) LRP5/ LRP6:
- Osteoporosis

Question 35

Growth Factors and Receptors

Answer 35

* A MAJOR ROLE OF GRWOTH FACTORS IS TO STIMULATE THE ACTIVITY FO GENES THAT ARE REQUIRED FOR CELL GROWTH AND CELL DIVISION!!!!**

• *** GROWTH FACTOR ACTIVITY IS MEDIATED BINDING TO SPECIFIC RECEPTORS: Ultimately influencing the Expression of Genes that can:
  1) Promote Entry of Cells into the Cell Cycle

2) Relieve Block on Cel Cycle Progression (Thus promoting Replication)
3) PREVENT APOPTOSIS
4) Enhance Biosynthesis of Cellular Components

Question 36

Epidermal Growth Factor (EGF)

Answer 36

SOURCES:
- Activated macrophages, salivary glands, keratinocytes, and many other cells

FUNCTIONS:
- Mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte Migration; stimulates formation of Granulation tissue

***** EGFR1 Mutations/ Amplifications in lung, head and neck, breast, and brain ERBB2 aka HER2 in certain breast cancers (monoclonal antibody therapy)

Question 37

Transforming Growth Factor Alpha

Answer 37

SOURCES:
- Activated macrophages, keratinocytes, many other cell types

FUNCTIONS:
- Stimulates proliferation of hepatocytes and many other epithelial cells

Question 38

Hepatocyte Growth Factor (HGF) (Scatter Factor)

Answer 38

SOURCES:
- Fibroblasts, Stromal cells in the Liver, endothelial cells

FUNCTIONS:
- Enhances PROLIFERATION of Hepatocytes and other epithelial cells; increases cell motility

**MET is the Receptor and is overexpressed in some cancers: kidney and thyroid ***

Question 39

Vascular Endothelial Growth Factor (VEGF)

Answer 39

SOURCES:
- Mesenchymal cells

FUNCTIONS:
- Stimulates proliferation of endothelial cells; Increases Vascular Permeability

** VEGF-A induces blood vessel development after injury and in tumors anti -VEGF antibodies have therapeutic implications***

Question 40

Platelet- Derived Growth Factor (PDGF)

Answer 40

SOURCES:
- Platelets, macrophages, endothelial cells, smooth muscle cells, keratinocytes

FUCNTIONS:
- Chemotactic for neutrophils, macrophages, fibroblasts, and smooth muscle cells; activates and stimulates proliferation of fibroblasts, endothelial, and other cells; stimulates ECM protein synthesis

** Recruitment of cells to sites of tissue injury and inflammation **

Question 41

Fibroblast Growth Factors (FGFs), Including ACIDIC (FGF-1) and BASIC (FGF-2)

Answer 41

SOURCES:
- Macrophages, mast cells, endothelial cells, many other cell types

FUNCTIONS:
- Chemotactic and mitogenic for fibroblasts; stimulates angiogenesis and ECM protein synthesis

** FGFR3 abnormalities lead to Achrondroplasia and Malignancies***

Question 42

Transforming Growth Factor Beta (TGF- Beta)

Answer 42

SOURCES:
- Platelets, T lymphocytes, macrophages,
endothelial cells, keratinocytes, smooth muscle cells, fibroblasts

FUNCTIONS:
- Chemotactic for Leukocytes and fibroblasts; stimulates ECM protein synthesis; SUPPRESSES Acute Inflammation

***** Drives scar formation and applies the brakes on inflammation that accompanies wound healing “pleiotropic with a vengeance”

Question 43

Keratinocyte Growth Factor (KGF) (i.e., FGF-7)

Answer 43

SOURCES:
- Fibroblasts

FUNCTIONS:
- Stimulates keratinocyte migration, proliferation, and differentiation

Question 44

Interaction of ECM

Answer 44

** CELL INTERACTIONS with ECM are CRITICAL for Development and Healing, as well as for maintaining Normal Tissue architecture.*

1) MECHANICAL SUPPORT:
- For cell anchorage and cell migration, and maintenance of cell polarity.

2) CONTROL OF CELL PROLIFERATION:
- By binding and displaying growth factors and by signaling through CELLULAR RECEPTORS of the integrin family. As discussed earlier, the ECM provides a depot for a variety of latent growth factors that can be activated within foci of injury or inflammation.

3) SCAFFOLDING FOR TISSUE RENEWAL:
- Because maintenance of normal tissue structure requires a BASEMENT MEMBRANE or Stromal Scaffold, the INTEGRITY OF THE BASEMENT MEMBRANE OR THE STROMA OF PARENCHYMAL CELLS IS CRITICAL for the organized regeneration of tissues. Thus, ECM disruption results in defective tissue regeneration and repair, as occurs in the development of liver cirrhosis following injury to the liver cells and the collapse of the hepatic storm.

4) ESTABLISHMENT OF TISSUE MICROENVIRONMENT:
- BASEMENT MEMBRANE acts as a boundary between epithelium and underlying connective tissue; it does not just provide support to the epithelium but is also functional. For example, in the kidney, it forms part of the filtration apparatus.

Question 45

Collagens

Answer 45

• Some collagen types (e.g., types I, II, III, and V collagens) form linear fibrils stabilized by interchain hydrogen bonding; such fibrillar collagens form a Major Proportion of the connective tissue in structures such as Bone, Tendon, Cartilage, Blood Vessels, and Skin, as well as in HEALING WOUNDS and particularly scars.
• Since this process is DEPENDENT ON VITAMIN C, children with ascorbate deficiency have skeletal deformities, and people of any age with vitamin C deficiency bleed easily because of weak vascular wall basement membrane, and heal poorly.
• Genetic defects in collagens cause diseases such as OSTEOGENESIS IMPERFECTA (OI) and certain forms of EHLERS-DANLOS SYNDROME

Question 46

Elastin

Answer 46

• The ability of tissues to Recoil and Recover their Shape after physical deformation is conferred by elastin ( Fig. 1-14 ).
• This is especially important in CARDIAC VALVES and for large blood vessels (that must accommodate recurrent pulsatile flow), as well as in the uterus, skin, and ligaments. Morphologically, Elastic Fibers consist of a central core of elastin with an associated mesh like network composed of fibrillin.
• The latter relationship partially explains why fibrillin synthetic defects lead to Skeletal Abnormalities and weakened Aortic Walls, as in individuals with MARFAN SYNDROME.

Question 47

Maintaining Cell Populations

Answer 47

*** Cell proliferation is fundamental to development, maintenance of steady- state tissue homeostasis, and replacement of dead or damaged cells *****

• Cell cycle driven by proteins called CYCLINS and enzymes called CYCLIN DEPENDENT KINASES (No Bad DNA IN)
• CDK INHIBITORS are the enforcer of the Quality control checkpoints (No Bad DNA OUT)

Question 48

Defective CDK1 Checkpoints

Answer 48

• Defective CDKI Checkpoint proteins allow cells with damaged DNA to Divide, resulting in Mutated Daughter Cells with the potential of developing into MALIGNANT TUMORS!!!!

Question 49

Stem Cells

Answer 49

• During development, stem cells give rise to all the various differentiated tissues; in the adult organism, stem cells Replace damaged cells and Maintain tissue populations as individual cells within them undergo replicative senescence due to attrition of telomeres.
• ** STEM CELLS ARE CHARACTERIZED BY TWO IMPORTANT PROPERTIES:
  1) SELF RENEWAL , which permits stem cells to maintain their numbers

2) ASYMMETRIC DIVISION, in which one daughter cell enters a differentiation pathway and gives rise to mature cells, while the other remains undifferentiated and retains its Self-Renewal Capacity.

Types of Stem Cells:
1) Embryonic Stem Cells (TOTIPOTENT)

2) Tissue Stem Cells (Adult Stem Cells) 2 Types:
a) HEMATOPOIETIC
b) MESENCHYMAL