The Cell

Topic Outline

I. OverviewII. Cell Membrane

A. LipidsB. ProteinsC. Carbohydrates

III. CytoplasmIV. Organelles

A. MitochondriaB. RibosomesC. Endoplasmic ReticulumD. Golgi ApparatusE. LysosomeF. PeroxisomeG. Cytoskeleton

1. Microtubules2. Intermediate Filaments3. Microfilaments

H. Nucleus1. Nuclear Envelope2. Chromatin3. Nuclear Pores4. Nucleolus5. Nucleoplasm6. Nuclear Matrix

OVERVIEWCELL

The cell is the basic morphological and functional unit of all living things. It has the capacity to perform all life functions and is therefore, under favorable environmental conditions, of independent existence.

With a cytoplasm enclosed in a plasma membrane and a nucleus located in the center.

MAJOR TYPES

Both types of cells have a plasma membrane which encloses the cytoplasm, genetic material (DNA) and ribosomes.

Prokaryotes -“before kernel” Eukaryote -“True kernel

II. Cell Membrane

FLUID-MOSAIC MODEL Integral proteins have the ability to float like icebergs in a phospholipid sea Presence of lipid rafts which move around

PLASMA MEMBRANE/ PLASMALEMMA Trilaminar in appearance when stained with osmium (lamina externa, lamina

intermedia, lamina interna) Composed of phospholipids, cholesterol, proteins, and chains of

oligosaccharides covalently linked to phospholipids and protein molecules.

FUNCTION Maintenance of structural integrity of cell Controlling movements of substances in and out of the cell (Selective

Permeability) Regulation of cell-to-cell interactions Recognition of antigens and foreign bodies via receptors Interface between cytoplasm and external environment Transduction of extracellular physical or chemical signals into intracellular

events Establishment of transport systems for specific molecules

A. LIPIDS

Contains a polar head (hydrophilic), located at the surface of the membrane and 2nonpolar fatty acyl tails (hydrophobic) projecting into center of the plasmalemma

Amphiphatic molecule Phospholipids, trigylcerides, cholesterol, glycolipids

1. GLYCOLIPID Located outside the cell\ One of the components of glycocalyx

2. PHOSPHOLIPID Consist of 2nonpolar (hydrophobic) long-chain fatty acids linked to a

charged polar (hydrophilic) head group Most abundant (e.g. lecithin) Organized into a double layer (bilayer) Exhibit trilaminar structure when stained in osmium tetrocide. Deposition of

stain in hydrophilic ends.

Predominant in plasma membrane Stained with osmium

3. CHOLESTEROL Breaks up the close packing of phospholipid long chains making the

membrane more fluid Almost 2% of plasma membrane’s weight Can be seen inside and outside of plasma membrane

4. SPHINGOLIPID any of a class of compounds that are fatty acid derivatives of sphingosine and

occur chiefly in the cell membranes of the brain and nervous tissue.

FACTORS AFFECTING MEMBRANE FLUIDITY

1. Temperature (↑Temp = ↑Fluidity)2. Unsaturated Fatty Acids (↑UFA = ↑Fluidity)3. Membrane Cholesterol Content(↑Cholesterol = ↓Fluidity)

Q&A: Each lipid molecule is amphipathic. -TRUE

B. PROTEINS

Constitutes 50% of membrane‘s weight; mostly globular

1. INTEGRAL PROTEINS Found embedded within the bilayer tightly bounded May require use of detergents in order to extract Cathing -accumulation of integral proteins

2. TRANSMEMBRANE PROTEINS Passes through the thickness of the membrane Frequently form ion channels and carrier proteins for transport Main form of hydrophilic channel Membrane receptors/transport Contain both hydrophilic and hydrophobic carbohydrate One-pass transmembrane proteins -passes through membrane once One that traverses the membrane Multipass transmembrane proteins -long and folded proteins which make

several passes through the membrane

3. PERIPHERAL MEMBRANE PROTEINS Loosely associated w/ the inner/ outer surface of membrane Associated with the cytoskeletal appearance

Functions in the intracellular secondary messenger system Also part of cytoskeleton, structural in nature More globular, sometimes filamentous Usually associated with integral proteins

C. CARBOHYDRATES

Resembles a fuzzy border (glycocalyx) around the cell Oligosaccharide moieties which project from the external surface

of the plasma membrane; glycoproteins and glycolipids Extends to extracellular environment Branching structure - tends to branch outward towards extracellular

matrixo Forms the cell coat or glycocalyxo For cell adhesion and recognition

Facilitate cell-to-cell interaction, cellular attachment of extracellular components, and in antigen-enzyme binding

FUNCTIONS Acts as cellular attachment to extracellular matrix components Acts as antigen binding surface Responsible for cell-to-cell recognition and interaction

III. CYTOPLASM Protoplasm enclosed in a membrane

IV. ORGANELLES

Membrane-bound enzyme containing subcellular compartments Actively participates in the metabolism of the cell

A. MITOCHONDRIA

Largest organelle (2to 6μm in length, 0.5μm in diameter) Contains circular DNA, mitochondrial ribosomes (mRNA, tRNA) and

enzymes for expression of mitochondrial genome Divides by fission, generated from preexisting mitochondria

FUNCTIONS Production of ATP via oxidative phosphorylation Considered the powerhouse of the cell Storing energy generated from cellular metabolite

PARTS1. OUTER MITOCHONDRIAL MEMBRANE

Very porous membrane, smooth contour Freely permeable to variety of small molecules

2. INNER MITOCHONDRIAL MEMBRANE Less porous, semi-permeable membrane Presence of infoldings (cristae) for increase in surface area for ATP synthase and respiratory chain

3. MATRIX Filled with dense fluid composed of at least 50%protein Contains enzymes for metabolic cycles and matrix granules which are

phospholipoproteins essential in sequestering Ca2+ from the cytosol to prevent calcium toxicity (happens during cell injury when calcium levels are dangerously high)

4. CRISTAE Folds in the inner membrane Increase ATP production Most abundant during high energy activities

5. INTERMEMBRANE SPACE Located between two membranes Continuous with intracristal space

6. INTERCRISTAL SPACE / MATRIX SPACE Holds the matrix

7. MATRIX GRANULES Mitochondrial Calcium ion conservation Binding sites for calcium

B. RIBOSOMES

Q&A: Ribosomes are bound to the nuclear membrane. -TRUE

C. ENDOPLASMIC RETICULUM System of interconnected tubules and vesicles whose lumen is referred to as cistern Synthesizing, packaging, and processing of different cellular substances

1. SMOOTH ENDOPLASMIC RETICULUM

System of anastomosing tubules and occasional flattened

membrane—bound vesicles Absence of ribosomes and ribophorins Abundant in adrenal cortex, liver, areas which synthesize

hormones Specialized SER: sarcoplasmic reticulum (skeletal muscle) -regulation

and sequestering of Ca2+ ions, assisting in control of muscle contraction

FUNCTIONS Synthesis of steroid, cholesterol, phospholipids triglycerides,

detoxification, lipid metabolism Glycogen breakdown

2. ROUGH ENDOPLASMIC RETICULUM Site where non-cytosolic proteins are synthesized Continuous with perinuclear cistern (space between inner and outer

nuclear membranes) Saclike, hasribosomes (granular) Presence of integral proteins for recognition and binding of ribosomes

towards the cytoplasmic sideo Docking proteino Pore proteino Ribophorin I and II -ribosome receptor protein

FUNCTIONS

Protein synthesis Plays a role in the post-translational modifications (sulfation, folding,

glycosylation) Manufactures lipids and integral proteins

Q&A: Smooth ER does NOT contain ribophorins. - TRUE (Ribophorin in an integral protein of RER.)

D. GOLGI APPARATUS

Located juxtanuclear; developed in neurons andglandular cells

Post-office of cell 3 major proteins:

o Cisternae (Golgi stack) - disk shapedo Vesicles- numerous small objects

peripheral to cisternaeo Vacuoles - located peripherally to the stack

of cisternae

3 levels of cisternae:o Cis-face (forming face) -closest to the RER; convex in shape and

considered to be the entry faceo Medial face (intermediate face)o Trans-face (maturing face) -concave in shape, considered to be

the exit face

FUNCTIONS

Post-translational modification and packaging of proteins from

the ER Polysaccharide synthesis

Concentration, modification, storage and packaging of secretory

products

PROTEIN TRAFFICKING1. ER vesicles are modified by Golgi apparatus (important for signaling) as it is transported and fused with the periphery of the cis-face of the Golgi apparatus2. Proteins are modified upon transfer from cis to medial and finally trans cisternae3. Budding of vesicles containing modified proteins at the trans Golgi network

4. Migration to designated target via vesicles Heterophagosomes – contain products of heterophagy (extracellular

origin) Autophagosomes – contain products of autophagy (primarily for

digestion of senescent organelles)

MECHANISMRER synthesizes, packages and postranslates CHON

↓Coat Protein Complex II (COPII) vesicles carry CHON from

RER to Cis-face of Golgi apparatus↓

CHON modification in Golgi apparatus starts at the Cis-face↓

COP I vesicles transfers the CHON from one cistern to anotherfor further modification until it reach the Trans-face

↓CHONs are packed in secretory vesicles for transfer to their

target membrane (through the guide of SNAREs)

Q&A: Golgi apparatus consists of several disk-shaped cisternae (saccules) arranged in a stack.

E. LYSOSOMES

Sites for cellular digestion Contains hydrolytic enzymes (acid phosphatase, ribonuclease, deoxyribonuclease, proteases, sulfatases, lipases, β-glucoronidase) Primary lysosomes - lysosomes that have not entered into a digestive event Secondary lysosomes - primary lysosomes that fuse with the membrane

of the phagosome and empty their hydrolytic enzymes into the vacuole for digestion to ensue

Residual bodies - indigestible compounds retained within the vacuoles; accumulation of residual bodies from long lived cell are called lipofuscin (wear and tear‘ pigment; they appear yellow-brown).

LYSOSOMES

F. PEROXISOMES

Self-replicating organelles containing oxidative enzymes Associates with SER Contains more than 40 oxidative enzymes (i.e. catalase, D-and

L-aminooxidases, hydroxyacid oxidase)

FUNCTION

Beta oxidation (lipid catabolism) degradation of hydrogen peroxide into water and

oxygenby catalase (hydrogen peroxide metabolism)Q&A: Which of the following organelles divide by fission? -MITOCHONDRIA & PEROXISOME

G. CYTOSKELETON Structural framework that provides integrity, helps incompartmentalizing

the organelles into distinct regions; permits transport of materials and is essential in cell division

Structural proteins for shaping cells, cell movement, movement of

organelles and intracytoplasmic vesicles

1. MICROTUBULES

Long, straight, rigid tubular appearing structures that act as intracellular

pathways α and β tubulin make up a tubulin dimer which make up a protofilament

and then form microtubules (13 protofilaments) Largest of the three

A. MICROTUBULE ASSOCIATED PROTEINS (MAPs) 2 motor proteins:

Dynein -bigger (2000kD), moves towards (-) end Kinesin -smaller (250 kD), moves towards (+) end

Movement requires ATP. Examples:

o Basal bodies of flagella and ciliao Centrosome

Functiono Provide rigidity and maintain cell shapeo Regulate intracellular movement of organelles and vesicles

B. CENTRIOLES Cylindrical in shape 350-500μm in length 50μm in diameter Subdistal and distal appendages present in mother centrioles but

not in daughter centrioles

CENTROSOME Contains centrioles and amorphous bodies (pericentriolar matrix/body) Centriole depolarization in S phase Function

o Structural organizero Control organelleo Vesicle and granule traffico Gives rise to basal bodies near nucleus

C. KINETOSOME (BASAL BODIES) Similar to centriole even in depolarization (follows an 8-triplet arrangement) Controls assembly of axoneme (extension from basal body to apical

region); occurs in cytoplasm Guides formation of appendages (cilia, flagella) Anchoring Points

D. CILIA or FLAGELLA Composed of 9peripheral doublets and 1unjoined pair of microtubules (9+2arrangement) Presence of dynein arms (ATPase activity) Radial spoke from each doublet going towards central pair Inner sheath with the central pair in the middle Parts

o Ciliary tip (+ end) - signaling moleculeo (9+2) axonemeo Transition zone - conversion from doublet formation to tripleto Basal body

During cell division, there are microtubules that form:1. MITOTIC SPINDLE MICROTUBULE - attached to the kinetochore2. POLAR MICROTUBULES - not incorporated with the spindle apparatus; from one centriole to another centriole3. ASTRAL FIBERS - extend from poles away from spindle and are for anchoring

2. INTERMEDIATE FILAMENTS

Very specific array of filaments Assist in the establishment and maintenance of the 3- D framework of the

cell

From a monomer → dimmer → tetramer (parallel dimer

arrangement) → 8-tetramer sheet → supercoiled sheet Examples

o Keratin - seen in skin, diverseo Vimentin - seen in mesenchyme, endothelial cells,

vascular smooth muscle cells, fibroblasts,chrondoblasts, macrophages

o Desmin - seen in skeletal and non-vascular muscle cellso Neurofilaments - seen in neuronso Nuclear lamins -fibrous network in nuclear membrane; low

bearing element; greatly affects morphology of the cello Glial fibrillary acidic protein (GFAP) - astrocytes,

oligodendrocytes, microglia, Schwann cells, ependymal cells, pituicytes

3. ACTIN FILAMENTS

Thinnest cytoskeleton and is located throughout the cytoplasm; forms irregular meshwork and exhibits polarity

Made up of G-actin -globular subunits, bound by profilin and thymosin, and F-actin -filamentousprotein which a forms double—stranded helix

Polymerization is controlled by Ca2+ and cyclic AMP levels Contractile activity results from interaction of actin and myosin Function

o Cellular contraction and movement

o Tension bearing and maintains integrity of the cell

H. NUCLEUS

Largest organelle of the cell; contains nearly all of the DNA May classified based on size (nucleus-cytoplasmic ratio), number,

chromatin pattern and location (basal, eccentric, central) 3 Major Components:

o Chromatin - genetic material of the cell (heterochromatin, euchromatin)

o Nucleolus - center for ribosomal RNA synthesiso Nucleoplasm - contains macromolecules and nuclear

particles involved in maintenance of cell

1. NUCLEAR ENVELOPE

Composed of 2 parallel unit membranes that fuse with each other at

certain regions to form perforations (nuclear pores), continuous with

RER Inner nuclear membrane (lined with nuclear lamina) and outer membranes separated by a perinuclear cistern Function

Helps control movement of macromolecules between nucleus

and cytoplasmo Molecular trafficking between cytoplasm and nucleuso Allows passive diffusion of ions and molecules;

acilitate receptors –mediated transport of signal bearing cargos

2. CHROMATIN Dark patches Less coiled portion

EUCHROMATIN For transcription of genetic structure-where the genetic material of the DNA molecules is being

transcribed into RNA Light stained

Active form

HETEROCHROMATIN

Tightly coiled inactive chromatin found in irregular clumps in the periphery of the nucleus Dark stained Inactive form

3. NUCLEAR PORES

Sites where the inner and outer membranes fuse Pathways between nucleus and cytoplasm are NOT OPEN but

showcase an octagonal pore complex made of 100+ proteins. –Only ions/molecules w/ diameter of up to 9nm can pass through w/o using energy.

Others use up ATP

4. NUCLEOLUS

Not membrane bound, not easily seen due to

heterochromatin content; site for rRNA synthesis; disappears before mitosis and appears right after mitosis

Largest and numerous in embryonic cells; in cellssynthesizing protein; malignant cells

PARTSA. PA (PARS AMORPHA)

Pale staining fibrillar center; associated with nucleolar organizer region (NORs) where newly synthesized

RNA are first seen here; contains inactive DNA

B. NUCLEONEMA Has 2 RNA components

C. PF (PARS FIBROSA) Density packed ribonucleolic fibers; newly synthesized rRNA appears here second

D. PG (PARS GRANULOSA) Dense granules representing maturing rRNA; appears here third

E. NUCLEOLUS-ASSOCIATED CHROMATIN Heterochromatin commonly associated with the nucleolus; no known function

5. NUCLEOPLASM

Protoplasm enveloped by the nuclear envelope

INTERCHROMATIN GRANULES (IG) 20-25 nm in diameter RNPs and enzymes (ATPase, GTPase, etc.) are found here Located in clusters; scattered throughout the nucleus

PERICHROMATIN GRANULES (PCG) 30-50 nm in diameter Located at the margins of the heterochromatin Surrounded by halo of less dense region Composed of densely packed fibrils

SMALL NUCLEAR RIBONUCLEOPROTEIN PARTICLES (snRNPs) Participate in splicing, cleaving and transporting

hnRNPs

HETEROGENOUS NUCLEAR RIBONUCLEOPROTEIN PARTICLES (hnRNPs) Complexes with mRNA precursors (pre-mRNA)

6. NUCLEAR MATRIX

Scaffolding Contains fibrillar elements, residual nucleoli and is supported by nuclear pore—nuclear lamina complex Associated with DNA replication sites, rRNA and mRNA transcription

and processing, steroid receptor binding, heat shock proteins, carcinogen binding, DNA viruses and viral proteins

7. CHROMOSOMES

Chromatin fibers that become condensed and tightly coiled during mitosis and meiosis; contains more than 99% of DNA; allows replication (using telomerase)

6 subunits per coil in strand of chromosome 4 types of histones in core with 2each kind (H2A, H2B, H4, H3)

with H1or H5histones outside nucleosome acting as strap 166 base pairs in central DNA 48 base pairs at linker region/link DNA At highly condensed state -1400 nm (occurs during metaphase)

Genomeo 23 pairs, of homologous chromosomes (22 autosomes, 1 sex

chromosome)o Sex chromatin (Barr body)o Chromatin - basis of level of activity (paler staining -more active)