CELL PHYSIOLOGY
Cell Theory
Cells were discovered in 1665 by Robert Hooke.
Early studies of cells were conducted by
- Mathias Schleiden (1838)
- Theodor Schwann (1839)
Schleiden and Schwann proposed the Cell
Theory.
The Cell Theory
• All living things are composed of cells
• Cell are the smallest unit of life
• All cells come from pre-existing cells
• The cell is the structural and functional unit of
life
Cell:
• Basic living unit of structure & fx of the body.
– > 100 trillion cells in body.
– very small (10-5 m in diameter), hence very
efficient.
– highly organized.
– variety of shapes & sizes.
– each type of cells has a special fx.
Cell (continued)
• All Cells share certain characteristics:
– general cell structure & components.
– general mechanisms for changing nutrients to Energy.
– deliver end products into their surrounding fluid.
– almost all have the ability to reproduce.
Eukaryotic Cells
Eukaryotic cells
-possess a membrane-bound nucleus
-are more complex than prokaryotic cells
-compartmentalize many cellular functions
within organelles and the endomembrane
system
-possess a cytoskeleton for support and to
maintain cellular structure
Eukaryotic Cells
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Cell Components
• What are the basic components of a cell?
– cell membrane
– nucleus
– cytoplasm
• cytosol
• organelles
Cell Nucleus
• Is a large spheroid body.
• Largest of organelles.
• Contains the genetic material (DNA).
• Most cells have a single nucleus.
• Enclosed by inner & outer membrane (nuclear
envelope).
– Outer membrane is continuous w ER.
• Nuclear pore complexes fuse inner & outer
membranes together.
– Selective active transport of proteins & RNA.
Nucleus
• Surrounded by a bilaminar nuclear membrane or envelope
with occasional pores
• One or more mobile nucleoli.
• The Nucleus contains almost all the DNA in the eukaryotic
cell
• It is responsible for the synthesis of mRNA, tRNA and rRNA.
NUCLEUS
• Nuclear Envelope
• double nuclear membrane each 2 nm thick
• The outer membrane is derived from the
endoplasmic reticulum
• The inner membrane from the nucleus
• Each is a separate lipid bilayer
• A perinuclear space, 10-50 nm wide separate
the two membranes.
NUCLEUS
• Nuclear Pores
• The nuclear envelope has several circular
nuclear pores (~1 nm wide).
• They occupy about 20% of the total surface
area of the nuclear envelop.
• Each pore is surrounded by 8 protein granules,
which serve as molecular sieves, allowing the
transport of materials such as RNA
NUCLEUS
Nuclear Lamina
• This is located between the inner nuclear
membrane and the nuclear chromatin.
• It is composed of complex polypeptides known
as laminins
• They undergo phosphorylation and
dephosphorylation at various stages of the cell
cycle.
NUCLEUS
• Nuclear Chromatin
• It is the Major constituent of the nucleus.
• It has a DNA : Proteins ratio of 1:2
• Half of these proteins are histones, the other
proteins are mainly transcription factors.
• Chromatin is made up of nucleosomes, each
consisting of 8 histone molecules surrounded by
DNA.
• Nucleosomes are joined together by an intervening
length of DNA known as “linker-DNA”.
NUCLEUS
Nucleolus
• These are intranuclear structures which stain
strongly for RNA and weakly for DNA.
• They float in the nuclear fluid
• It is the site for synthesis of ribosomal RNA
(rRNA)
• It is also the site for the assembly of ribosomal
subunits.
NUCLEUS
• Nuclear DNA
• Mammalian DNA is arranged in linear chromosomes
• It exists as a double helix held together by hydrogen bonds,
with the two strands being complementary.
• It has Adenine being bound to Thymine (A-T) while Guanine
is bound to Cytosine (G-C)
• Usually expressed as a number of nucleotide or base pairs
(bp).
• Human haploid genome has 2.8 x 109 bp
• Only a small part of the genome contains actual ‘genes’
CELL CYTOPLASM
THE CYTOPLASM
• The aqueous (fluid, jellylike substance)
content of a cell, that lies b/w cell membrane
& nucleus in which organelles are suspended.
• Serves as matrix (ground substance) in which
chemical reactions occur
• Cytoplasm is divided functionally into
– Cytosol (fluid portion of the cytoplasm)
– Inclusions including non membranous organelles
– Membranous Organelles (Functional units of the
cell)
Composition and function of cytosol
• Dissolved glucose, proteins and electrolytes
• enzymes
• transport proteins (Steroid Hormones & Metals)
• glycogen granules
• triacylglycerol droplets (adipocytes)
• Cytosol functions (many in conjunction with other
processes)
– Cell signaling
– Cytokinesis
– Protein synthesis
– many other chemical reactions e.g. Glycolysis, gluconeogenesis
The Inclusions
– They have direct contact with the cytosol
• Free Ribosomes
–Involved in synthesis of proteins
• Proteasomes
–Involved in protein degradation
• Protein fibers
–Provide structure and movement
within the cell
Membranous organelles
• Mitochondria
• The Endoplasmic reticulum
• The Golgi complex
• Lysosomes
• Peroxisomes
• Phagosomes
• secretory vesicles
• Centrosome/Centrioles
Mitochondria
• subdivisions of the matrix
• Have their own DNA and Ribosomes
• Replicate independently of Endosymbiotic theory
– Believed to have been prokaryotes that formed a symbiotic
relationship with precursor eukaryotic cells
• Are have varied shapes ,sizes and location in the cell.
• They are usually elongated, tubular (spherical in stress) about
3µm long and 0.5-1,5µm wide
• Each has a continuous external limiting membrane and an
inner membrane folded into septae (cristae)
• Cristae create partial the nucleus
• Also, Mitochondrial inheritance is purely maternal!
THE MITOCHONDRIA
• Serves as the "powerhouse of the cell" by
generating chemical energy
• Site of the tricarboxylic acid cycle and production
of NADH
• Oxidation of NADH in the electron transport
chain to produce ATP (H+ concentration higher in
the inter-membrane space than in the matrix)
• Stores energy as adenosine triphosphate (ATP) and
subsequently releases it when required by the cell
Functions of the mitochondria
• β-Oxidation of fatty acids
• Synthesis of intermediate metabolites required
for the biosynthesis of haem, glucose, steroids
and urea
• Detoxification of ammonia
• Accumulation/storage of divalent cations such
as Ca++
• Is curial in apoptosis
The Endoplasmic reticulum
• They are a complex network of membranes within
the cytoplasm which are folded extensively to form
vesicles, tubules and sacs usually as parallel pairs.
– Continuous with the outer membrane of the
nuclear envelope
– Two forms - smooth and rough
• When they have ribosomes attached to them, they
are granular in appearance and are called rough ER
• But when no/few ribosomes are present, they are
referred to as smooth ER.
Rough E R
• Network of flattened membrane sacs that create a network
of channels throughout the cytoplasm. They contain enzymes
that recognize and modify proteins
• Ribosomes are attached to the outside of the RER and
make it appear rough
• They synthesize proteins to be secreted, sent to
lysosomes or the plasma membrane
• Proteins are modified as they move through the RER
• Once modified, the proteins are packaged in transport
vesicles for transport to the Golgi body
Smooth ER
• Tubular membrane structure continuous with RER
• The smooth ER has roles in gluconeogenesis, plasma
lipoprotein production, synthesis of triacylglycerol,
cholesterol, phospholipids and other membrane lipids.
• Formation of bile salts
• Synthesis, secretion and inactivation of steroid hormones
• detoxification of foreign compounds and conjugation
reactions.
• sequestration of Ca2+ ions
• oxidative metabolism by the cytochrome P450 system.
Golgi Apparatus
The Golgi complex
• Its structure is similar to that of smooth
endoplasmic reticulum. It comprised of flattened
stacks of interconnected membranes in cisternae
or vesicular form, arranged like a stack of plates
• It forms a functional unit with the ER.
• Usually located near the nucleus.
• Some of its vesicles have special names such as
endosomes (involved in endocytosis) and
secretory vesicles (involved in hormone
secretion).
Functions of the Golgi Complex
• Proteins (packaging Vesicle) formed in the rough ER
passes through the cis-face and binds to the first layer
of the Golgi body.
• Its contents enter the Golgi complex for modification
and subsequently exits through the trans-face into
secretory channels, lysosomes, the plasma membrane
or to become part of the GC itself.
• The proteins and lipids are modified (as they pass
through layers of the Golgi complex) through multiple
post-translational modifications including further
glycosylation (initial glycosylation occurs in the ER)
Golgi Apparatus
– Molecular tags are added to the fully modified
substances
• These tags allow the substances to be sorted and packaged
appropriately.
• Tags also indicate where the substance is to be shipped.
• Functionally, the Golgi apparatus completes the
processing of substances received from the ER, Sorts
them, tag them and package fully processed proteins and
lipids into vesicles which are released via the trans face.
Putting it all together
– DNA directs RNA synthesis RNA exits
nucleus through a nuclear pore ribosome
protein is made proteins with proper
code enter RER proteins are modified in
RER and lipids are made in SER vesicles
containing the proteins and lipids bud off
from the ER
Putting it all together
ER vesicles merge with Golgi body
proteins and lipids enter Golgi each is
fully modified as it passes through layers of
Golgi modified products are tagged,
sorted and bud off in Golgi vesicles …
Golgi vesicles either merge with the plasma
membrane and release their contents OR
remain in the cell and serve a purpose
lysosomes
• The lysosome is an example of an organelle made at the
Golgi apparatus.
– Golgi packages digestive enzymes in a vesicle. The vesicle
remains in the cell (primary lysosome)
• They have the thickest membrane and contains a battery
of hydrolytic enzymes (acid hydrolases).
• They are abundant in some cell types such as
macrophages but scarce in others such as lymphocytes.
• Their enzymes are synthesized in the rough ER and
processed through the Golgi complex before passage
into the lysosomes.
Functions of lysosome
• The hydrolytic enzymes in lysosomes include
nucleases,, proteases (cathepsins), lipases and
glycosidases,
• They generally have low degree of specificity.
• These enzymes function best at a pH of between 4.0
and 5.5. They have a proton-pumping ATPase that
allows its lumen to be acidified to a pH of 5.
• The enzymes help in digesting dead cells
(endolysosomes), foreign cells and
proteins(phagolysosome), albumin in the renal tubules,
and in the remodeling of bones and other tissues
Lysosomes
• Tay-Sachs disease occurs when the lysosome
is missing the enzyme needed to digest a lipid
found in nerve cells.
– As a result the lipid accumulates and nerve cells
are damaged as the lysosome swells with
undigested lipid.
– This lysosomal storage disease causes mental
retardation and blindness
Phagosomes
• Are membrane bound bodies containing
materials ingested by phagocytosis
• To effect digestion they combine with
lysosomes to produce phagolysosomes
• Forms residual or dense bodies when
ingestible material remains
undigested/partially digested
Peroxisomes
• They are Spherical or spheroidal sacs, about 0.5-1.5 microns
in diameter.
• Also bounded by a single membrane.
• Formed by division of pre-existing peroxisomes.
• Their proliferation is stimulated by certain drugs e.g
clofibrate.
• They contain peroxidase and catalase enzymes which prevents
the build-up of peroxides in cells.
• They are also capable of the β -oxidation of fatty acids
• They sub serve detoxification function
• Degrade purines to uric acid
• Formation of bile acids and myelin sheath of nerves.
Centrioles or Centrosomes
• These are two short cylinders visible only
during cell division
• They are located near the nucleus and are so
arrange such that they are at right angles to
each other
• They are functionally concerned with
movement of the chromosomes during cell
division
Ribosomes
• Are small granules of Ribonucleoprotein particles
formed by the combination of rRNA and proteins
in the nucleolus.
• They are found embedded to the rough
endoplasmic reticulum
• They control synthesis of proteins required for
intracellular metabolism by forming complexes
with mRNA during protein synthesis, creating
polysomes (several ribosomes rolling along a
strand of mRNA in the course of protein synthesis).
The cytoskeleton
• The cytoskeletal components help to
– Maintain cell shape
– Organize the internal compartment of the cell
– Provide transport routes within cells
– Aid in creation of tissues from cells
– Create movement
• Along with motor proteins such as
Myosins – Actin motor protein
Dyenins
Kinesins Microtubule motor proteins
Other cellular motors proteins include:
ATP synthase, DNA & RNA polymerase
Microtubules and Microfilaments
• Microtubules are long hollow structures
approx.25 nm in diameter;make up strutures or
tracts on which chromosomes,mitochondria and
secretion granules move from one part of the cell
to another
• Microfilaments are long solid fibers 4 – 6 nm in
[Link] comprise the contractile protein
actin are responsible for cell motion
• Anticancer drugs binds to microtubules and
makes them stable, preventing the movement
stopping mitosis and eventually the cells die