HAP-31806 Molecular Regulation of Health and Disease (HAP31806)
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Lecture notes molecular regulation of health and disease
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HAP-31806 Molecular Regulation of Health and Disease (HAP31806)
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Wageningen University (WUR)
Here you find my notes of all the lectures of the course. I discuss and explain each slide of the lectures, giving a nice overview of all the contents.
HAP-31806 Molecular Regulation of Health and Disease (HAP31806)
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Part 3 – Alternative fuels for cell function and survival
Video 1 Autophagy explanation
Apart from glucose and glutamine, other metabolites or nutrients are important for cancer cells,
especially in conditions where cancer cells need to survive.
These conditions are: low glucose and hypoxic conditions. If there are alternative fuels, this would
allow the cancer cell to choose different substrates.
3 different pathways for alternative fuels for cancer cells:
1. Autophagy
2. Fatty acid oxidation
3. Protein uptake (micropinocytosis)
Autophagy – (eating yourself)
this is one of the breakdown pathways.
Parts of a cell, larger or smaller chunks,
are broken down into vacuoles, these
vacuoles fuse with the lysosome and in
the lysosome, these constituents of the
vacuole are then broken down.
Two different autophagy mechanisms:
a. Selective
certain organelles are tagged or marked
for degradation.
b. Non-selective
,Video 2 – molecular regulation of autophagy
There are 3 phases for phagophore formation:
Phase 1
ATG13 binds to ULK1, ATG17 is recruited, ATG extracts the lipid membranes from
other parts of the cell.
,Phase 2
second complex of BECLIN-1 and Ptdlns3K
instigates the initiation of the phagophore
formation.
Phase 3
Recruitment of other Atg
related proteins. And you
get membrane elongation
of this Atg complex, which
is coating and protecting
the membrane from
breaking it down. This will
result in making more of
the membrane and making
a complete phagophore.
Autophagosome fuses with
lysosome. Lysosome is an
organel which takes care of the
waste within a cell. A lysosome
has an acidic environment, lots
of enzymes, which can
breakdown macromolecules.
The smaller constituents are
released into the cell again.
These constituents can be used
as fuel or for making building
blocks.
, Video 3 - Fatty acid oxidation (1 of 2) Stem cells and cpt1c
Fatty acids can be used as an
alternative fuel for cancer cell
survival.
A tumour does not only consist of cancer cells.
cancer stem cells are a different type of cancer
cell.
Cancer stem cells:
- Quiescent cells in tumors that are resistant to therapy
- Low metabolic rates
- Set to survive instead of proliferation
- Eradicating these cells would prevent disease relapse and residual disease
- Are able to renew the cancer cell pool
- Aslo called Tumor Initiating Cells (TICs), dormant tumor cells
Cancer stem cells rely on different fuels than glucose and glutamine, for example fatty acids and
autophagy.
Fatty acid oxydation
Palmitate is one of the fatty acids. Fatty acids are turned
into a solubel form (palmitoyl -CoA, the CoA part makes it
possible for fatty acids to be transported into the cell).
Fatty acid oxydation takes place in the mitochondria. To be
transported into mitochondria, palmitoyl-CoA is turned into
palmitoyl -carnitine. It is then turned back into palmitoyl-
CoA and then there is fatty acid oxydation → acetyl-CoA.
Acetyl-CoA goes into TCA cycle.
CPT1 is the rate limiting step in fatty acid oxydation.
CPT1c can also play a role in tumour growth.
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