L11- Immunometabolism Flashcards
What are the purposes of metabolic reactions in organisms?
Catabolism (breakdown) of nutrients to produce energy in order to build components needed by the organism (anabolism)
Waste elimination
What is glycolysis?
The conversion of glucose to pyruvate
Produces biosynthetic intermediates for other processes
Anaerobic process
Produces low amount of ATP
What are the biosynthetic intermediates produced by glycolysis?
G6P- nucleotides (pentose phosphate pathway)
3PG- amino acids (serine)
Pyruvate- TCA cycle
What is the citric acid/TCA cycle?
Set of reactions involving pyruvate that produces NADH and FADH which are reduced in oxidative phosphorylation to produce large amounts of ATP.
Occurs in mitochondria under normoxia
What is Fatty Acid Oxidation?
Lipids are broken down into fatty acids then acetyl co-A which enters the TCA cycle to produce large amounts of ATP
What is glutaminolysis?
Glutamine enters TCA cycle as alpha-keto-glutarate and is broken down to produce ATP
What is the pentose phosphate pathway?
Metabolic pathway parallel to glycolysis
Produces nucleotides from G6P
What is fatty acid and cholesterol biosynthesis?
Synthesis of fatty acids, triacylglycerol, phospholipids and cholesterol from acetyl-co-A
What are the metabolic regulators?
HIF1alpha and mTOR sense oxygen and nutrients (amino acids, glucose) in the cell.
They will then signal to the cell to carry out more glycolysis (anabolism) in the presence of abundant glucose to produce ATP.
When ATP is high AMP kinase inhibits mTOR and promotes catabolism of energy stores and inhibits anabolism.
What process do naive immune cells use to produce energy?
Mainly oxidative phosphorylation
What happens to energy production once naive immune cells encounter antigen?
Increased signalling by mTOR and HIF1alpha
Naive cells transform into Effector T cells
What process do effector T cells use to produce energy?
Mainly glycolysis due to its fast activation and generation of metabolites to support growth and differentiation.
They do this independent of oxygen concentration.
What do memory cells use to produce energy?
Mainly fatty acid oxidation for steady levels of energy
What do regulatory T cells use to produce energy?
Normally oxidative phosphorylation, fatty acid oxidation and cholesterol biosynthesis
How does GAPDH regulate immune function in T cells?
GAPDH (glycolytic enzyme) binds to mRNA in resting immune cells to prevent transcription
When antigen is encountered the GAPDH becomes engaged in glycolysis leaving mRNA free to be transcribed to produce interferon gamma protein
