Cellulaire biochemie | Nicky Janssen
DICTAAT CELLULAIRE BIOCHEMIE
BIO-FARMACEUTISCHE WETENSCHAPPEN, JAAR 2
UNIVERSITEIT LEIDEN
1
, Cellulaire biochemie | Nicky Janssen
Thema I: Cellulaire groei en energie
1. Hallmarks of cancer (proliferatie)
Sustained proliferative signaling results in cell division.
2. Cell cyclus
Verschillende fasen
- G1 à cellgroei en development
Requires ATP
Protein production
RNA synthesis
Organelle production allowing for DNA synthesis
- Synthesis (DNA)
Requires ATP
Protein/enzyme synthesis required for DNA replication
Synthesis & replication of DNA
Synthesis of organelles required for cell division
- G2 à production of microtubule
Requires ATP
Continues growth of cell
Nucleus enveloped in nuclear envelope
Formation and division of centrioles
Doubling of chromosomes
Synthesis of proteins, mRNA and organelles
- M
3. Energie en metabolisme à kan veranderen in kankercellen waardoor ze sneller kunnen gaan
groeien
ATP wordt gemaakt in de mitochondria.
De netto-opbrengst van het proces is 36 ATP
2
, Cellulaire biochemie | Nicky Janssen
Glucose gaat erin. Ook al in het cytoplasma wordt ATP gemaakt. ATP is ook nodig voor de glycolyse.
Het ATP gaat het mitochondrion in en dan komt de citroenzuurcyclus. Door middel van
elektronentransport, fosforylatie, krijgen we een enorme hoeveelheid ATP.
ATP zorgt er onder andere voor dat de cel kan delen.
4. SRB-assay à meten van celgroei
Leerdoelen
- 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, met gebruik van standaard
potentialen, evenwichtsreacties en kinetische parameters.
- Je kunt uit data van biochemische en celbiologische technieken afleiden welke resultaten zijn
gevonden (SRB)
Hallmarks of cancer
Cancer is when abnormal cells divide in an uncontrolled way. Abnormalities are normally due to gene
changes which impact the cell cycle. There are over 100 types of cancer. Finding an unique type is
difficult.
There are 6 hallmarks on which all cells of cancer can be recognized.
1. Sustaining proliferative signaling
Cells have a receptor at the surface, which, when receiving a growth factor signal from neighboring
cells, initiates a cellular cascade of signaling which leads to cell growth and division.
Cells normally need this signaling from other cells to know when to divide, ensuring that proliferating
happens in an coordinated way.
Cancer cells are able to divide even without receiving signals from other cells which lead to an
uncontrolled proliferation of these abnormal cells.
3
, Cellulaire biochemie | Nicky Janssen
It is often a mutation in the receptors’ that maintains a growth signaling cascade, even in absence of
the signal. With each replication cycle, the mutation is passed on to the daughter cells. This
uncontrolled proliferation could lead to the formation of a mass which we call a tumor.
2. Evading growth suppressors
In order to maintain homeostasis, along with growth factors, cells can also produce growth
suppressors which act as a stop signal for themselves or neighboring cells if they are growing in an
uncoordinated way. However, cancer cells happen to ignore these anti-grow signals. This also
contributes to continuous calibration of the cancer cell.
So, these mutated cells are dividing without control.
3. Resistance to cell death
Cells have an inner system to recognize dangerous mutations and initiate apoptosis. These mutated
cells do not do apoptosis.
Cancer cells often have a mutation in the signaling proteins leading to cell death, which helps them
evade this faith.
4. Enabling replicative immortality
Cells have a natural expire date, after which they are destined to die. Some cancer cells overcome this
expire date and can divide indefinitely.
5. Inducing angiogenesis
Cancer cells secrete molecules which stimulate blood vessel growth.
4
DICTAAT CELLULAIRE BIOCHEMIE
BIO-FARMACEUTISCHE WETENSCHAPPEN, JAAR 2
UNIVERSITEIT LEIDEN
1
, Cellulaire biochemie | Nicky Janssen
Thema I: Cellulaire groei en energie
1. Hallmarks of cancer (proliferatie)
Sustained proliferative signaling results in cell division.
2. Cell cyclus
Verschillende fasen
- G1 à cellgroei en development
Requires ATP
Protein production
RNA synthesis
Organelle production allowing for DNA synthesis
- Synthesis (DNA)
Requires ATP
Protein/enzyme synthesis required for DNA replication
Synthesis & replication of DNA
Synthesis of organelles required for cell division
- G2 à production of microtubule
Requires ATP
Continues growth of cell
Nucleus enveloped in nuclear envelope
Formation and division of centrioles
Doubling of chromosomes
Synthesis of proteins, mRNA and organelles
- M
3. Energie en metabolisme à kan veranderen in kankercellen waardoor ze sneller kunnen gaan
groeien
ATP wordt gemaakt in de mitochondria.
De netto-opbrengst van het proces is 36 ATP
2
, Cellulaire biochemie | Nicky Janssen
Glucose gaat erin. Ook al in het cytoplasma wordt ATP gemaakt. ATP is ook nodig voor de glycolyse.
Het ATP gaat het mitochondrion in en dan komt de citroenzuurcyclus. Door middel van
elektronentransport, fosforylatie, krijgen we een enorme hoeveelheid ATP.
ATP zorgt er onder andere voor dat de cel kan delen.
4. SRB-assay à meten van celgroei
Leerdoelen
- 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, met gebruik van standaard
potentialen, evenwichtsreacties en kinetische parameters.
- Je kunt uit data van biochemische en celbiologische technieken afleiden welke resultaten zijn
gevonden (SRB)
Hallmarks of cancer
Cancer is when abnormal cells divide in an uncontrolled way. Abnormalities are normally due to gene
changes which impact the cell cycle. There are over 100 types of cancer. Finding an unique type is
difficult.
There are 6 hallmarks on which all cells of cancer can be recognized.
1. Sustaining proliferative signaling
Cells have a receptor at the surface, which, when receiving a growth factor signal from neighboring
cells, initiates a cellular cascade of signaling which leads to cell growth and division.
Cells normally need this signaling from other cells to know when to divide, ensuring that proliferating
happens in an coordinated way.
Cancer cells are able to divide even without receiving signals from other cells which lead to an
uncontrolled proliferation of these abnormal cells.
3
, Cellulaire biochemie | Nicky Janssen
It is often a mutation in the receptors’ that maintains a growth signaling cascade, even in absence of
the signal. With each replication cycle, the mutation is passed on to the daughter cells. This
uncontrolled proliferation could lead to the formation of a mass which we call a tumor.
2. Evading growth suppressors
In order to maintain homeostasis, along with growth factors, cells can also produce growth
suppressors which act as a stop signal for themselves or neighboring cells if they are growing in an
uncoordinated way. However, cancer cells happen to ignore these anti-grow signals. This also
contributes to continuous calibration of the cancer cell.
So, these mutated cells are dividing without control.
3. Resistance to cell death
Cells have an inner system to recognize dangerous mutations and initiate apoptosis. These mutated
cells do not do apoptosis.
Cancer cells often have a mutation in the signaling proteins leading to cell death, which helps them
evade this faith.
4. Enabling replicative immortality
Cells have a natural expire date, after which they are destined to die. Some cancer cells overcome this
expire date and can divide indefinitely.
5. Inducing angiogenesis
Cancer cells secrete molecules which stimulate blood vessel growth.
4
