Lecture 1 – Cellular Respiration
Introduction
Cell replication
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Eukaryotic cells – mitosis
Prokaryotic cells – binary fission
The number of cells in the human is around 1 billion per gram of tissue (all derived from a single cell
- the fertilised egg!)
Average human weighs 70 kg (70 000 g) – therefore around 70 trillion cells!!
Large numbers of cells must replicate often, and replication must be precisely regulated.
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Repair of damaged tissue
Growth of an organism
Replace old and dying cells
Studying the Cell Cycle
Normal human cells can be grown in culture (in vitro)
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Vitro – glass (Latin)
Human cells will not divide indefinitely
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Human fibroblasts will go through 25 - 40 cell divisions
Then enter replicative cell senescence
Can still metabolise but will not replicate
Immortalised human cells
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Human cells can undergo mutations that allow them to continue to grow indefinitely in
culture. These are referred to as cell lines.
o Mutations can occur naturally – cells derived from human cancers (the most
commonly used is a human cell line derived from a cervical cancer biopsy called
HeLa cells)
 Henrietta Lacks – a working-class African-American woman living near
Baltimore. The cells were taken without the knowledge or permission of her
or her family, and they became the first human cells to grow well in a lab.
o Mutations can also be induced
The Cell Cycle
G0 – resting state
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Cells may exit the cycle at G1 and enter a stage designated G0
Often referred to as quiescent or senescent - they are still metabolically active but may be
terminally differentiated (never divide again).
G0 can be followed by re-entry into the cell cycle.
o Most lymphocytes in human blood are in G0. However, with proper stimulation, such as
encountering the appropriate antigen, they can be stimulated to re-enter the cell cycle
at G1
G0 represents an active repression of the genes needed for mitosis
Interphase
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Appears to be inactivate microscopically
Longest part of the cell cycle
Comprised of:
1. G1 – cell growth
o first phase after cell division
o most variable in length
o cells mature and make more cytoplasm and organelles
o normal metabolic activities occur
o preparation for S-phase
o cell requires an external signal (external growth factors) to exit this phase and move into
S phase
2. S – DNA synthesis
o Replication of DNA and histones
3. G2 – cell growth
o Cell prepares for division
o Synthesis of materials needed for mitosis (eg. spindle fibres, proteins, organelles,
microtubules and centrioles)
Mitosis
1. Prophase
o Chromatin condenses
o Nuclear membrane breaks down
o Centrosomes move apart
o Spindle poles starts to form
2. Pro-metaphase
o Spindle fibres form and attach to kinetochores
3. Metaphase
o Chromosomes are pulled to the equatorial plane and line up in the centre of the cell
4. Anaphase
o Centromeres divide
o Spindle fibres shorten and poles move apart
o Breakdown of kinetochore proteins, spindle fibres pull sister chromatids to opposite
sides of the cell
5. Telophase
o Spindle breaks down and chromosomes elongate
o Nuclear membrane is re-formed
6. Cytokinesis
o the cell membrane pinches in at the cell equator, forming a cleft called the cleavage
furrow
o cell separation into two daughter cells
Term
Centromeres
Centrosome
Kinetochore
Spindle fibres
Spindle poles
Definition
A region of highly condensed DNA at the centre of a pair of sister chromatids,
where the kinetochores are assembled
A non-membranous, nucleus-associated organelle which acts as the major
microtubule-organizing centre in eukaryotic cells
A large protein complex located at the centromere of a chromosome, where
spindle fibres are attached during cell division
A network of filaments formed during cell division and responsible for the
movement and segregation of chromosomes
The location to which the centrosomes migrate during mitosis of eukaryotic
cells
Spindle Fibres
Mitosis requires the formation of a new apparatus called the spindle
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The chromosomes are separated by the mitotic spindle
The spindle is a symmetrical, bipolar structure composed of microtubules that extend
between two poles.
At each pole is a centrosome.
Spindle formation and function depend on the dynamic behaviour of microtubules and their
associated motor proteins
The spindle is a complex assembly of microtubules and microtubule–dependent motor proteins. •
The microtubules are highly organized with respect to their polarity.
The centrosome (located at the spindle poles) is a negatively charged organelle.
Fixed at negative end – centrosome
Positive end – grows towards positive
Lengthening – adding more and more microtubule proteins
Can grow and reach out by lengthening
Able to anchor the centrosomes to the cell membrane
Poles are anchored to cell membrane (?)
Creates tension, holds chromosomes in central equatorial plane
Equal tension in both directions – cell proceeds into anaphase
Associated motor proteins
Variation in Cell Cycle Length
Early embryonic cell cycle
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Rapid cell division
No growth periods between synthesis and mitosis
Very well-regulated process – replication occurs in synchrony
Cell Proliferation in Adults
Some cells never divide:
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Lens cells (of the eye)
Nerve cells
Cardiac muscle cells
Some cells do not normally divide but can be stimulated to do so. These include:
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skin fibroblasts
smooth muscles
endothelial cells (line blood vessels)
epithelial cells (lung, liver, kidney, etc)
Cells that divide often include:
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Embryonal
Haematopoietic (blood stem cells)
Epithelial stem cells of the skin and digestive tract