BFW 2 – Cellulaire Biochemie
, BFW 2 – Cellulaire Biochemie
Thema I: Cellulaire Groei & Energie
Dit thema gaat over wat er gebeurt in de cel wanneer signaaltransductie en gen
transcriptie/translatie hebben plaatsgevonden. Wat is het effect van de signalen in de
cel? En hoe zit het in kankercellen?
Hier worden thema's als "Hallmarks of Cancer", waarbij we dieper in gaan op proliferatie
en cel deling. Je zal leren over energie regulatie, metabolisme en hoe we cel proliferatie
kunnen meten.
Leerdoelen Thema I
• Je kunt de verschillen tussen het metabolisme van een 'gezonde' cel en een
kankercel benoemen.
• Je kunt uitleggen welke metabolische processen zorgen voor groei en progressie
van kanker.
• Je kunt berekeningen uitvoeren aan de vrije energie in een cel.
• Je kunt de methodiek van de SRB en IF techniek uitleggen.
• Je kunt uit data van SRB en IF assays afleiden welke resultaten zijn gevonden.
• Je kunt uit een artikel met biochemische en celbiologische data de relevante
vraagstelling en conclusie extraheren om een onderzoeksvraag voor een
vervolgonderzoek te bedenken.
PREP I
1.0 Hallmarks of Cancer
Cancer cells exhibit several key characteristics that allow them to grow, survive, and
spread uncontrollably. These traits arise from genetic mutations and environmental
changes in the cells, forming the basis of tumor development and progression.
1. Sustaining Proliferative Signaling: Cancer cells bypass the normal need for
external growth signals by mutating receptors, enabling them to continuously
divide and form tumors. They generate their own growth signals or overexpress
receptors that constantly stimulate cell growth.
2. Evading Growth Suppressors: Cancer cells ignore signals from tumor
suppressor genes, like p53 and retinoblastoma protein (Rb), which would
normally halt cell division. This unchecked proliferation leads to tumor formation.
3. Resisting Cell Death: Mutations in cancer cells allow them to evade apoptosis,
the programmed cell death process that normally eliminates damaged or
dangerous cells. They balance pro-apoptotic and anti-apoptotic proteins to resist
self-destruction.
, BFW 2 – Cellulaire Biochemie
4. Enabling Replicative Immortality: Normal cells have a limit on the number of
times they can divide, but cancer cells overcome this by activating the enzyme
telomerase, which maintains telomere length, granting them the ability to divide
indefinitely. A well-known example is the HeLa cell line.
5. Inducing Angiogenesis: Cancer cells stimulate the growth of new blood vessels
(angiogenesis) to supply themselves with the necessary nutrients and oxygen for
continued growth and division.
6. Activating Invasion and Metastasis: Tumor cells break down cell adhesion and
the extracellular matrix, enabling them to invade surrounding tissues and spread
to distant parts of the body through the bloodstream or lymphatic system.
7. Avoiding Immune Destruction: While the immune system often detects and
destroys small tumors, larger tumors evolve mechanisms to evade immune
detection, allowing them to grow unchecked.
8. Tumor-Promoting Inflammation: Chronic inflammation can promote cancer
development by creating an environment that supports tumor growth, recruiting
immune cells that release growth factors and cytokines.
9. Genome Instability and Mutation: Cancer cells mutate constantly to adapt and
survive, leading to an unstable genome. Mutations in genes such as BRCA1 and
BRCA2 contribute to this process, further enabling cancer progression.
10. Deregulating Cellular Energetics: Cancer cells undergo a shift in energy
metabolism, favoring aerobic glycolysis (Warburg effect) over more efficient
energy production methods. This allows them to produce more building blocks
for rapid cell growth, despite inefficient energy extraction.
These hallmarks illustrate the complexity of cancer, highlighting the various
mechanisms tumor cells use to thrive and evade destruction. Understanding these
traits is crucial for developing targeted cancer therapies.
2.0 Cel Cyclus
Om te kunnen delen moeten cellen de cel cyclus doorlopen. In dit onderdeel gaat het
over de verschillende fasen van de cel cyclus, en over hoe deze wordt gereguleerd in
cellen.
2.1 Introductie over de algemene celcyclus met de daarbij betrokken fases.
The video "Cell cycle phases" explains the stages of the cell cycle, drawing parallels to
the seasons of the year. The cell cycle has two main phases: interphase and mitosis.
1. Interphase is where most cells spend the majority of their time. It involves
growth but not division, and consists of three sub-phases:
o G1 phase (Gap 1): The cell grows and produces organelles and proteins.
This is the longest phase of the cell cycle.
, BFW 2 – Cellulaire Biochemie
o S phase (Synthesis): The cell duplicates its DNA, resulting in 46 pairs of
chromosomes (from 23 pairs originally).
o G2 phase (Gap 2): The cell prepares for mitosis by creating structures like
microtubules to pull chromatids apart during cell division.
2. Mitosis (M phase): The cell actively divides into two daughter cells. After mitosis,
each daughter cell re-enters the G1 phase to begin the cycle again.
Certain cells, like neurons, may exit the cycle entirely and enter a dormant phase called
G0, where no further division occurs.
The video also highlights how cancer cells differ from normal cells by prioritizing
division over growth due to mutations that disrupt normal regulation.
2.3 Cyclin-dependent kinases (CDKs) en hoe deze de celcyclus reguleren.
These cyclin-CDK complexes ensure that the cell cycle progresses smoothly, either by
inhibiting proteins that block DNA replication or promoting proteins required for cell
division.
The video "Cell cycle control | Cells | MCAT | Khan Academy" explains the regulatory
mechanisms of the cell cycle, focusing on two main checkpoints:
1. G1/S checkpoint: This checkpoint ensures that the cell is ready for DNA
replication. If conditions are not favorable, the cell will not proceed to the S
phase (DNA synthesis).
2. G2/M checkpoint: This checkpoint ensures that the cell is prepared for mitosis,
verifying that DNA replication has been successfully completed before cell
division begins.
Key regulatory proteins are involved in these processes:
• Cyclin-dependent kinases (CDKs): Enzymes that add phosphate groups to
other proteins, activating or deactivating them. CDKs are always present in the
cell but are inactive by default.
• Cyclins: Proteins that bind to CDKs to activate them. Different cyclins are
produced at specific times during the cell cycle, controlling its progression.
For example:
• At the G1/S checkpoint, Cyclins D and E: Activate CDK-2 and CDK-4 in G1,
leading to the phosphorylation of the RB protein, which inhibits DNA replication.
When RB is phosphorylated, DNA replication is no longer blocked, allowing the
cell to move to the S phase.
• Cyclin A: Produced in the S phase and activates DNA replication by binding to
CDK-2.
• Cyclin B: Produced in G2, binds to CDK-1 to initiate mitosis.
, BFW 2 – Cellulaire Biochemie
Thema I: Cellulaire Groei & Energie
Dit thema gaat over wat er gebeurt in de cel wanneer signaaltransductie en gen
transcriptie/translatie hebben plaatsgevonden. Wat is het effect van de signalen in de
cel? En hoe zit het in kankercellen?
Hier worden thema's als "Hallmarks of Cancer", waarbij we dieper in gaan op proliferatie
en cel deling. Je zal leren over energie regulatie, metabolisme en hoe we cel proliferatie
kunnen meten.
Leerdoelen Thema I
• Je kunt de verschillen tussen het metabolisme van een 'gezonde' cel en een
kankercel benoemen.
• Je kunt uitleggen welke metabolische processen zorgen voor groei en progressie
van kanker.
• Je kunt berekeningen uitvoeren aan de vrije energie in een cel.
• Je kunt de methodiek van de SRB en IF techniek uitleggen.
• Je kunt uit data van SRB en IF assays afleiden welke resultaten zijn gevonden.
• Je kunt uit een artikel met biochemische en celbiologische data de relevante
vraagstelling en conclusie extraheren om een onderzoeksvraag voor een
vervolgonderzoek te bedenken.
PREP I
1.0 Hallmarks of Cancer
Cancer cells exhibit several key characteristics that allow them to grow, survive, and
spread uncontrollably. These traits arise from genetic mutations and environmental
changes in the cells, forming the basis of tumor development and progression.
1. Sustaining Proliferative Signaling: Cancer cells bypass the normal need for
external growth signals by mutating receptors, enabling them to continuously
divide and form tumors. They generate their own growth signals or overexpress
receptors that constantly stimulate cell growth.
2. Evading Growth Suppressors: Cancer cells ignore signals from tumor
suppressor genes, like p53 and retinoblastoma protein (Rb), which would
normally halt cell division. This unchecked proliferation leads to tumor formation.
3. Resisting Cell Death: Mutations in cancer cells allow them to evade apoptosis,
the programmed cell death process that normally eliminates damaged or
dangerous cells. They balance pro-apoptotic and anti-apoptotic proteins to resist
self-destruction.
, BFW 2 – Cellulaire Biochemie
4. Enabling Replicative Immortality: Normal cells have a limit on the number of
times they can divide, but cancer cells overcome this by activating the enzyme
telomerase, which maintains telomere length, granting them the ability to divide
indefinitely. A well-known example is the HeLa cell line.
5. Inducing Angiogenesis: Cancer cells stimulate the growth of new blood vessels
(angiogenesis) to supply themselves with the necessary nutrients and oxygen for
continued growth and division.
6. Activating Invasion and Metastasis: Tumor cells break down cell adhesion and
the extracellular matrix, enabling them to invade surrounding tissues and spread
to distant parts of the body through the bloodstream or lymphatic system.
7. Avoiding Immune Destruction: While the immune system often detects and
destroys small tumors, larger tumors evolve mechanisms to evade immune
detection, allowing them to grow unchecked.
8. Tumor-Promoting Inflammation: Chronic inflammation can promote cancer
development by creating an environment that supports tumor growth, recruiting
immune cells that release growth factors and cytokines.
9. Genome Instability and Mutation: Cancer cells mutate constantly to adapt and
survive, leading to an unstable genome. Mutations in genes such as BRCA1 and
BRCA2 contribute to this process, further enabling cancer progression.
10. Deregulating Cellular Energetics: Cancer cells undergo a shift in energy
metabolism, favoring aerobic glycolysis (Warburg effect) over more efficient
energy production methods. This allows them to produce more building blocks
for rapid cell growth, despite inefficient energy extraction.
These hallmarks illustrate the complexity of cancer, highlighting the various
mechanisms tumor cells use to thrive and evade destruction. Understanding these
traits is crucial for developing targeted cancer therapies.
2.0 Cel Cyclus
Om te kunnen delen moeten cellen de cel cyclus doorlopen. In dit onderdeel gaat het
over de verschillende fasen van de cel cyclus, en over hoe deze wordt gereguleerd in
cellen.
2.1 Introductie over de algemene celcyclus met de daarbij betrokken fases.
The video "Cell cycle phases" explains the stages of the cell cycle, drawing parallels to
the seasons of the year. The cell cycle has two main phases: interphase and mitosis.
1. Interphase is where most cells spend the majority of their time. It involves
growth but not division, and consists of three sub-phases:
o G1 phase (Gap 1): The cell grows and produces organelles and proteins.
This is the longest phase of the cell cycle.
, BFW 2 – Cellulaire Biochemie
o S phase (Synthesis): The cell duplicates its DNA, resulting in 46 pairs of
chromosomes (from 23 pairs originally).
o G2 phase (Gap 2): The cell prepares for mitosis by creating structures like
microtubules to pull chromatids apart during cell division.
2. Mitosis (M phase): The cell actively divides into two daughter cells. After mitosis,
each daughter cell re-enters the G1 phase to begin the cycle again.
Certain cells, like neurons, may exit the cycle entirely and enter a dormant phase called
G0, where no further division occurs.
The video also highlights how cancer cells differ from normal cells by prioritizing
division over growth due to mutations that disrupt normal regulation.
2.3 Cyclin-dependent kinases (CDKs) en hoe deze de celcyclus reguleren.
These cyclin-CDK complexes ensure that the cell cycle progresses smoothly, either by
inhibiting proteins that block DNA replication or promoting proteins required for cell
division.
The video "Cell cycle control | Cells | MCAT | Khan Academy" explains the regulatory
mechanisms of the cell cycle, focusing on two main checkpoints:
1. G1/S checkpoint: This checkpoint ensures that the cell is ready for DNA
replication. If conditions are not favorable, the cell will not proceed to the S
phase (DNA synthesis).
2. G2/M checkpoint: This checkpoint ensures that the cell is prepared for mitosis,
verifying that DNA replication has been successfully completed before cell
division begins.
Key regulatory proteins are involved in these processes:
• Cyclin-dependent kinases (CDKs): Enzymes that add phosphate groups to
other proteins, activating or deactivating them. CDKs are always present in the
cell but are inactive by default.
• Cyclins: Proteins that bind to CDKs to activate them. Different cyclins are
produced at specific times during the cell cycle, controlling its progression.
For example:
• At the G1/S checkpoint, Cyclins D and E: Activate CDK-2 and CDK-4 in G1,
leading to the phosphorylation of the RB protein, which inhibits DNA replication.
When RB is phosphorylated, DNA replication is no longer blocked, allowing the
cell to move to the S phase.
• Cyclin A: Produced in the S phase and activates DNA replication by binding to
CDK-2.
• Cyclin B: Produced in G2, binds to CDK-1 to initiate mitosis.
