100% satisfaction guarantee Immediately available after payment Both online and in PDF No strings attached
logo-home
COMPLETE SUMMARY HAP31806 $7.41
Add to cart

Summary

COMPLETE SUMMARY HAP31806

 1 purchase
  • Course
  • Institution

Summary of the course molecular regulation of health and disease. Includes all themes.

Preview 4 out of 48  pages

  • October 20, 2022
  • 48
  • 2022/2023
  • Summary
avatar-seller
SUMMARY Molecular regulation of health and disease HAP-31806

THEME 1 – Molecular regulation of energy and nutrient metabolism
Part 1: Cancer and metabolism
Hallmarks of cancer:
- Sustaining proliferative signaling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
- Resisting cell death

Sustaining growth signaling:
- Abnormal receptors (always activated)
- Produce their own activation signals
- Activation of downstream signaling pathways

Resisting cell death:
- Tumor cells escape programmed cell death
- Tumor cells are set to survive even when damaged
- Cell death programs are altered

Evading anti-growth:
- Tumor suppressors block cell proliferation when cells are damaged (P53, Rb)
- Tumor suppressors are often mutated in cancers

Replication potential:
- Altered telomerases: instead of shortening (normal cells) -> enhancement of
telomerase activity -> synthesis and extension of telomeric DNA ->
- Continued replication
- Immortal cells in culture

Angiogenesis:
- Lack of nutrients drives angiogenesis
- Activating blood vessel formation (VEGF)
- Immune cell infiltration promotes angiogenesis

Invasion / metastasis:
- Cells undergo epithelial to mesenchymal transition -> spread to distant sites

Other hallmarks:
- Avoiding immune destruction
- Tumor promoting inflammation
- Genome instability and mutation
- Deregulation cellular energetics

Metabolic hallmarks: sustaining proliferation signaling deregulating cellular energetics


1

,Cell metabolism makes biomass and energy:
Biomass = protein, DNA, membrane; Energy = ATP

Glycolysis: glucose -> pyruvate
Anaerobe oxidation of pyruvate: pyruvate -> lactate
Aerobe oxidation of pyruvate in TCA: pyruvate -> lactate
FA oxidation: FA -> FAO -> into TCA (FAO en TCA in mitochondrion)
ATP and NASH are generated: glucose – ATP → pyruvate
Glutaminolysis: glutamine -> glutamate -> TCA
Lipogenesis for membranes: lipids from TCA and glutamate ->
membrane
PPP to DNA: from glycolysis -> PPP -> ribonucleotides -> DNA
AA used for protein synthesis

Cancer cell metabolism




Proliferation: metabolic reprogramming to maximize: biomass, energy (ATP)
Survival: metabolic reprogramming to maximize: alternative fuels, anti-oxidants defense

Part 2: Glucose and glutamine use in cancer and normal cells
The Warburg effect:
Warburg experiment: + glucose; - glucose
- glucose with cells; + glucose with cells; + glucose no cells
- pH decreased= acidification
- measurement: pressure decrease = O2 consumption
o pressure increase = CO2 production
▪ lactic acid exchanges protons with bicarbonate to form CO2



2

,Warburg’s first discovery: tumors have high rate of lactic acid formation
Pasteur effect: high O2 inhibits glycolysis in yeast (in culture)

Second experiment: according to Pasteur effect, when O2 present -> no glycolysis but that
was not what Warburg saw:
- 10x more glucose consumed in fermentation to lactate as compared to glucose
consumed during respiration (in the presence of oxygen)
- Aerobe glycolysis (glycolysis in the presence of oxygen) -> thus, tumor cells have
glycolysis in the presence of oxygen

Why did Warburg thought that mitochondria are dysfunctional in cancer cells: normal cells
can lower glycolysis when using mitochondria, and cancer cells cannot -> reasoned because
mitochondria are damaged.
Purpose of mitochondria in cancer cells: mitochondria are essential for making building
blocks but also for making NADH and regenerating NAD>
Upregulated enzymes and genes from the glycolytic pathway regulate the Warburg effect.

Warburg effect: rate of glucose uptake increases, and lactate is produced even in the
presence of oxygen and fully functioning mitochondria.

The benefits of the Warburg effect on cancer cells:




Rapid ATP synthesis:
Glycolysis: glu -> pyruvate -> lactate + 2 ATP
Glucose oxidation: glu -> pyruvate -> CO2/H20 + ~30 ATP
→ glycolysis responds to increasing ATP demand




3

, Biosynthesis:
Increased glucose utilization is used as carbon source for anabolic processes needed to
support cell growth
Glycolytic pathway is needed to build DNA
PPP: G6P/F6P/G3P -> turn into ribose; 3PG -> turn into glycine
Ribose and glycine are precursors for nucleotides -> DNA
PPP: also produces NADPH = essential for biosynthetic pathways and antioxidant defense

Tumor microenvironment:
Altering the tumor microenvironment:
- Acidification promotes invasiveness
- Taking away the glucose from native immune cells (glucose competition)

Cell signalling:
Inactive transcription / active transcription (by histone acetylation)




Glutamine and cancer cell metabolism
Glutamine = essential metabolite for cancer cells (growth)
Glutaminolysis = breakdown of glutamine to pyruvate / lactate -> via mitochondria
(glycolysis is in cytosol)
Pyruvate and glutamate -> building blocks for membranes

Reductive carboxylation: not losing the isotype -> is incorporated into
citrate and other metabolites as oxaloacetate (OAA)
→ allows biosynthesis during hypoxia

Glutamine into lipids via 1) cytosolic route or via 2) mitochondrial route
2. mitochondrial route: reductive carboxylation of alpha-kG into citrate




4

The benefits of buying summaries with Stuvia:

Guaranteed quality through customer reviews

Guaranteed quality through customer reviews

Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.

Quick and easy check-out

Quick and easy check-out

You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.

Focus on what matters

Focus on what matters

Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!

Frequently asked questions

What do I get when I buy this document?

You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.

Satisfaction guarantee: how does it work?

Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.

Who am I buying these notes from?

Stuvia is a marketplace, so you are not buying this document from us, but from seller v7777777. Stuvia facilitates payment to the seller.

Will I be stuck with a subscription?

No, you only buy these notes for $7.41. You're not tied to anything after your purchase.

Can Stuvia be trusted?

4.6 stars on Google & Trustpilot (+1000 reviews)

65539 documents were sold in the last 30 days

Founded in 2010, the go-to place to buy study notes for 15 years now

Start selling
$7.41  1x  sold
  • (0)
Add to cart
Added