LECTURE #1: THE CELL AS A UNIT OF HEALTH AND DISEASE

study of suffering

Pathology literally is the ________

study of disease

Pathology represents the _______

3.2 billion DNA pairs

Human genome has ______

1.5%

Only ___ of genome is used to encode proteins

98.5%

____ of the human genome does not encode protein

1. Promotor and Enhancer Regions

2. Binding Sites

3. Noncoding Regulatory RNAs (mircoRNA, and lncRNA)

4. Mobile Genetic Elements

5. Special Structure Regions of DNA (centromeres, and telomeres)

CLASSES OF FUNCTIONAL NON-PROTEIN CODING SEQUENCES (5)

1. Single Nucleotide Polymorphism

2. Copy Number Variation

2 MOST COMMON FORMS OF DNA VARIATION

HISTONES ARE DYNAMIC

Regulated by host of nuclear proteins and chemical modifiers.

Histone Methylation

Maybe associated with either transcriptional activation or repression

Histone Acetylation

This type of modification tends to open up chromatin and increasing transcription. The opposite occurs in deacetylation

Histone Phosphorylation

Serine residues can be modified by phosphorylation and DNA can be opened or condensed

DNA methylation

High levels of DNA methylation results in transcriptional silencing.

MICRO-RNA AND LONG NONCODING RNA

• These are some mechanisms of gene regulation

• The two are transcribed but not translated

Chromatin Organizing Factors

Non coding regions believed to be important in regulating spatial relationships between genes.

Micro-RNA (miRNA)

FUNCTION: post transcriptional silencing of gene expression

Individual micro-RNA can regulate multiple protein encoding genes

Small Interfering RNA (siRNAs)

Short RNA sequence that can be introduced experimentally in cells

Small Interfering RNA (siRNAs)

Serve as substrate for DICER and interact with RISC similar to that of miRNAs

Small Interfering RNA (siRNAs)

Being developed as possible therapeutic agents to silence pathologic genes

Long Noncoding RNA (IncRNA)

Modulate gene expression by several mechanisms

Rough Endoplasmic Reticulum

Synthesizes protein for plasma membrane or points beyond

Golgi Body

Physically assembles the protein

Ribosomes

Produces protein intended for cytosol

Smooth Endoplasmic Reticulum

Used for steroid hormone and lipoprotein synthesis as well as modification of hydrophobic compounds into water soluble molecules, storage of calcium in muscles, detoxification

Lysosomes

Intercellular organelles that contain digestive enzymes that permit digestion of protein, polysaccharides, lipids, and nucleaic acid

Proteasomes

Specializes in degrading denatured proteins and releasing peptides

Peroxisomes

Specializes in breakdown of fatty acids and reactive oxygen species.

Endosomal Vesicles

Shuttle internalized material to intracelllular sites or newly formed material to cell surface or target organelle.

Cytoskeleton

Responsible for cell movement within the cell and environment. Also maintains intracellular organizations.

Mitochondria

Produces most of the ATP, source of intermediate metabolites, synthesis of certain molecules. Contain sensors of cell damage that can initiate and regulate apoptosis.

PASSIVE TRANSPORT

Uses concentration or electrical gradient between inside and outside of cell that drives solute movement

ACTIVE TRANSPORT

Goes against concentration gradient and accomplish by carrier molecules using energy released by ATP hydrolysis

PASSIVE MEMBRANE DIFFUSION

Small nonpolar molecules like O2 and CO2 readily dissolves in membrane

PASSIVE MEMBRANE DIFFUSION

Also, hydrophobic molecules (steroid-based molecules) also pass easily.

PASSIVE MEMBRANE DIFFUSION

Small polar molecules also pass like water, ethanol and urea.

PASSIVE MEMBRANE DIFFUSION

Barrier to larger polar molecules, and ions

CARRIERS AND CHANNELS

For larger polar molecules that must cross membrane a unique plasma membrane protein is usually required.

CHANNEL PROTEINS

Create hydrophobic pores which when open permit rapid movement of solutes based on size and charge

CHANNEL PROTEINS

Binds specific solute and undergo conformational change that transfers ligand across membrane

ENDOCYTOSIS

Uptake of fluids or macromolecules.

PINOCYTOSIS

A type of Endocytosis in which fluids are taken by the cell .

EXOCYTOSIS

Process by which large molecules are exported from cells.

TRANSCYTOSIS

Movement of endocytosed vesicles between the apical and basolateral compartments of cells.

CYSTOSKELETON & CELL TO CELL INTERACTIONS

Ability of cell to adopt a shape, maintain polarity, organize organelles and move about depends on the cytoskeleton.

• Actin

• Intermediate filaments

• Microtubules

MAJOR CYTOSKELETAL PROTEIN (3)

globular protein actin (G Actin)

IN ACTIN:

5-9 nm diameter formed from _______

long filaments

IN ACTIN:

G Actin polymerize into _____ (F actin) that intertwine to form double stranded helices

protein myosin

IN ACTIN:

In muscle F actin binds with filamentous ______

1. 10 nm diameter that comprise heterogeneous family

2. Lamin A, B and C

3. Vimentin

4. Desmin

5. Neurofilaments

6. Glial Fibrillary Acid Protein

7. Cytokeratins

INTERMEDIATE FILAMENTS (7)

MICROTUBULES

25 nm thick fibrils composed of polymerized dimers of alpha and beta tubulin

MICROTUBULES

Within cells the move vesicles, organelles or other molecules

MICROTUBULES

Also form cilia or flagella

1. Kinesins for anterograde

2. Dyneins for retrograde transport.

TWO VARIETIES of Microtubules

CELL TO CELL INTERACTIONS

Provide mechanics links and enable surface receptors to recognize ligands on their cell.

junctions

CELL TO CELL INTERACTIONS:

Cells interact and communicate via _____

1. Occluding (tight) junction,

2. Anchoring (desmosomes) junction

3. Communicating (gap) junction

THREE BASIC TYPES OF JUNCTIONS

CELL SIGNALING

Extracellular Signaling Pathways based on distance

PARACRINE

Signals cells within immediate vicinity

AUTOCRINE

Cell signals itself

neurotransmitter, synapse

Substance (_____) released into space called ____ where it then lands to receptor on adjacent cell

hormone

Substance (____) is released into blood stream and travel to distant site to affect its target cell.

1. Mechanical Support

2. Control of Cell Proliferation

3. Scaffolding for Tissue Removal

4. Establishment of Tissue Microenviorment

KEY FUNCTIONS OF EXTRACELLULAR MATRIX

1. Interstitial Matrix

2. Basement Membrane

TWO BASIC FORMS OF EXTRACELLULAR MATRIX

1. Fibrous Structural Proteins

2. Water Hydrated Gels

3. Adhesive Glycoproteins

COMPONENTS OF EXTRACELLULAR MATRIX (3)

1. G1 presynthetic growth

2. S DNA synthesis

3. G2 Premitotic growth

4. M Mitotic

5. G0 Not actively cycling

PROLIFERATION AND CELL CYCLE (5)