Molecular Cell Biology & Disease Flashcards
1
Q
Learning Outcomes
A
- Outline some of the major causes of molecular diseases.
- Describe the molecular causes of several example diseases
- Autophagy
- Recycling of cellular proteins, etc.
- Cystic fibrosis (and cholera)
- a mutation of a transport protein (channelopathy) and in cholera
transport itself not the problem, but control of the channel is, due to
disruption of second messenger cascade (in this case cAMP). - Muscular Dystrophies
- Mechanotransduction of motor proteins to the cytoskeleton /
membrane
2
Q
Causes of disease
A
- Genetic mutations due to heredity / radiation / chemical
- Infectious agents (animals, fungi, bacteria, viruses, prions)
- Chemical agents (drugs, industry, heavy metals)
- Direct trauma
- And these can affect…
- Structural molecules of cells
- Enzymes & Biochemical Pathways Cell Signalling/Regulation
- Cell Membrane Transport
- Many of the above and more …….
3
Q
Problems…
A
- Structural molecular problems
- Genetic etc.
- Prions (mad cow’s disease / KJS in humans / Parkinson’s)
- Chemical denaturation (industrial exposure)
- Overstimulation (e.g. temporary hearing loss & receptor protein
change)
4
Q
Problems…
A
- Cell membrane transport problems
- Channelopathies (e.g. congenital deafness, cystic fibrosis, heart
diseases) - Problems with regulation of membrane transport (e.g. diarrhoea,
cholera)
4
Q
A
the 2016 Nobel Prize in Physiology
or Medicine
Yoshinori Ohsumi
“for his discoveries of mechanisms
for autophagy”
5
Q
Problems…
A
- Cell signalling problems
- Neurochemical release & reuptake (e.g. mental illness/drug
intoxication) - Intracellular second messenger problems (e.g. cholera)
- Hormonal Imbalance (secretion, reception – e.g. gigantism,
dwarfism) - Other problems with pathways for cell signals & reception (e.g.
cancer)
5
Q
Problems…
A
- Enzyme function problems
- Turning enzymes on via regulatory pathways
- Turning enzymes off via regulatory pathways
- Blocking enzymatic pathways
- Absence of enzymes
5
Q
Autophagy – “self eating”
A
- Autophagosomes are transient membranous orgnls
- They form, then engulf cellular contents, such as damaged proteins
and organelles. - Fuses with the lysosome, where the contents are degraded into
smaller constituents.
6
Q
Autophagy – “self eating”
A
- Lysosomes contain enzymes for digestion of cellular
contents.
7
Q
Autophagy – “self eating”
A
- Clears old/damaged proteins
and provides the cell with
nutrients and building blocks
for renewal.
8
Q
A
- Microautophagy:
- Lysosome itself engulfs small components of the cytoplasm by inward
invagination of the lysosomal membrane.
8
Q
A groundbreaking experiment!
A
- Ohsumi used yeast cells where vacuoles are lysosomes
- If he could disrupt the degradation process in the vacuole while the
process of autophagy was active, then autophagosomes should
accumulate within the vacuole - Cultured mutated yeast lacking vacuolar degradation enzymes and
simultaneously stimulated autophagy (starvation) - Ohsumi then studied thousands of yeast mutants and identified 15
genes that are essential for autophagy
8
Q
A
- Macroautophagy (dominant):
- An isolation membrane (phagophore) sequesters a small portion of the
cytoplasm, including soluble materials and organelles, - Now called an autophagosome → fuses with the lysosome (autolysosome)
- Degrades materials contained within it.
9
Q
Mechanisms of Autophagy
A
- 3 classes: macroautophagy, microautophagy, and chaperonemediated autophagy.
9
Q
A
- Chaperone-mediated autophagy.
- Proteins directly translocate across the lysosomal membrane during
chaperone-mediated autophagy. The chaperone protein Hsc70 (heat shock
cognate 70) recognize proteins, Lamp-2A acts as a receptor on the lysosome,
and unfolded proteins are delivered into the lysosomal lumen through a
translocation complex.
10
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14
Q
Loss of CFTR function manifests cystic fibrosis
pathophysiology
A
15
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16
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CFTR gating
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23
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24
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Duchenne V Becker MDs
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25
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Duchenne V Becker MDs
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