64 - Mitochondrial Energy Pathways Flashcards
Reducing powers generated by oxidative phosphorylation
NADH and FADH2
Where are NADH and FADH2 oxidised in ATP generation?
Electron transport chain
Role of pentose phosphate pathway
Generation of NADPH for reductive biosynthesis of reduced glutathione and reductive biosynthesis of proteins and nucleic acids.
Oxidation in organic chemistry
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2
Decreases electron density on carbon by:
- Forming one of these: C-O, C-S; C-N; and C-X (X: F, Cl, Br or I), or
- Breaking this: C-H; C-C
Broad principle of generation of reducing agents with ATP generation pathways
Dehydrogenation (oxidation) leads to H+ joining with NAD- or FADH- to form NADH or FADH2.
This can happen in TCA cycle, fatty acid oxidation
Role of complexes I to IV in electron transport chain
Generate a protein gradient across the inner membrane of mitochondria, to be pushed through ATP synthase to generate ATP.
What donate H+ to complexes I to IV for oxidative phosphorylation?
NADH (complexes I to IV) and FADH2 (complexes II to IV)
Role of flavin mononucleotide (FMN) and ubiquinone
Electron conveyors that are readily oxidised and reduced.
Move electrons in oxidative phosphorylation
Coenzyme Q role
Accept electrons from electron transport chain, which are used to generate water.
Effect of coenzyme Q buildup
If the process of CoQ accepting e- is slowed down too much, you can get a buildup of CoQ, which reduces O2 to superoxide
What catalyses glutathione synthesis?
Glutathione reductase
Main pathway in NADPH generation in the cytosol
Pentose phosphate pathway
Role of glutathione
Can rescue oxidised proteins
Oxidative stress role in cancer cell apoptosis
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- Oxidative damage to DNA
- Activation of tumour suppressor p53 in nucleus
- Expression of proteins inducing cell cycle arrest and cell death
Warburg effect
Most cancer cells generate ATO through glycolysis, even with normal O2 levels.
Most cancer cells therefore convert glucose to lactate and do not metabolise it in TCA cycle and oxidative phosphorylation.
Why do cancer cells often generate a very acidic environment?
Warburg effect
Under normal conditions, what happens to lactate generated by glycolysis?
Lactate secreted from cells, goes to liver, used as a substrate for gluconeogenesis
GLUT activity in cancer cells
GLUT1 overactivity
How can cancers be imaged?
Give 2-deoxy 2(18F)fluoro-D-glucose to patient, which accumulates in cancer cells (because of overactive GLUT1 receptors)
Using a PET scan to image this.
More common H+ carrier in mitochondria
NADH is higher concentration in mitochondria, lower in cytosol.
NADPH is the opposite.
Stages of pentose phosphate pathway at which NADPH is generated.
Two stages:
One for forming NADPH to form glutathione.
One for forming NADPH for generation of fatty acids, sterols, etc (reductive biosynthesis)
Effect of Warburg effect and hypoxia-induced metabolic adaptation in cancer cells
Scavenge ROS, which prevents DNA damage in nucleus and mitochondria, which prevents activation of p53.
Adaptations of tumour cells to tumour microenvironment (hypoxia, low pH, autophagy)
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ATP, NADPH generation (glycolysis and pentose phosphate pathway)
Precursors for synthesis of DNA, protein
Glutathione synthesis to reduce ROS
Molecule that starts pentose phosphate pathway
Glucose-6-phosphate
Rationale behind Warburg effect
Warburg effect represents a type of metabolic adaptation of cancer cells to avoid cell senescence and promote cell growth and proliferation
