Lecture notes from Imperial College London, Medical Biosciences BSc course, 2nd year, Cancer Biology module.
Cancer metabolism lecture notes: cancer cells adapt their metabolism to be able to grow and divide rapidly.
Cancer cells grow and divide very rapidly, it is one of the established hal...
Cancer Metabolism
Hallmarks of cancer
- ‘hallmarks of cancer’: generic characteristics that cancers have in common
- cell division: duplicate all cellular constituents
=> high demand for building blocks: amino acids, lipids, nucleotides, carbohydrates
/ fat
(sugars)
Cancer metabolism - an emerging hallmark of cancer
- genetic reprogramming of cancer cells
=> provide selective advantage during tumorigenesis
=> support cell survival under stressful conditions
=> allow growth & proliferation at pathologically elevated levels
- cancer cells have unique metabolic requirements to cope with growth needs (nutrients, E & waste)
=> emerging hallmark: deregulating cellular energetics/ reprogramming of energy metabolism
=> alterations: increased bioenergetics - increased biosynthesis - alteration redox balance
=> occur early in tumorigenesis or later during metastasis
Increased bioenergetics
- E primarily derived from glucose
=> glycolysis - oxidative decarboxylation - TCA cycle (Krebs cycle) - oxidative phosphorylation
- glycolysis: break down (lysis) of glucose in the cytoplasm => converted to pyruvate
, - oxidative decarboxylation in mitochondrial matrix: from pyruvate to acetyl-CoA
2 carbon atoms = acetate ; CoA = coenzyme A
- TCA cycle: used to release stored E through oxidation of acetyl-CoA (acetate) into CO2 and H2O
Generate ATP &
reducing equivalents
CO2
H20
NADH & FADH2
(e- donors)
(inner membrane mitochondria)
oxidative phosphorylation of NADH & FADH2 generated
in the electron transport chain (requires oxygen)
=> E in the form of ATP by chemiosmosis (through
harnessing of chemosmotic gradient made by pumping H+)
Oxygen requirement in normal and cancer cells
- tumour cells can exist in a low nutrient & low oxygen (0-2% in the centre) environment
- O2 conc decreases the further tumour cells are from blood vessels: hypoxic & necrotic centre
= hyperoxia/ normoxia
- mechanisms to detect & monitor levels of O2
=> ex: hypoxia inducible factor (HIF-1a): oxygen sensing transcription factor
=> normoxic conditions: targeted for degradation
=> hypoxic conditions: degradation prevented => binds DNA & activate response genes
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