Host-bacteria metabolism Flashcards
What is an M0 macrophage?
A naive macrophage waiting to be activated
What are the two types of macrophages?
M1 microbicidal
M2 Tissue repair
What is the process called when an M0 differentiates?
Macrophage polarisation
What are the 4 roles of macrophages?
Sample, Heal, Inhibit and Present.
Do M0 have a high or low metabolism?
Generally low.
Where do M0 get the majority of their ATP from?
The TCA, with less from the PPP and glycolysis.
Which metabolic pathways are significantly reduced in M2?
PPP and glycolysis.
Which pathways does the M2 use for the majority of its energy?
Beta oxidation of fatty acids.
Glutamine metabolism.
In M2, what does arginase convert arginine to?
Ornithine and urea.
What purpose does ornithine serve in M2?
Helps with cell proliferation.
What sort of activity do PFK-2 and FBPase-2 have?
Phosphatase activity.
What is the main source of ATP in M1 polarised macrophages?
Glycolysis.
How do M1 ensure they have enough glucose for glycolysis?
They increase their uptake
What other metabolic pathways are activated?
PPP and fatty acid synthesis.
In M1, what is arginine metabolised by?
Nitric oxide synthase
What happens to the TCA in M1 and why?
It is largely stopped as some of the intermediates are used up in other places.
What sort of activity do PFK-2 and FBPase-2 have in M1
Predominantly kinase in order to activate glycolysis.
In M1, what forms NADPH?
The Pentose Phosphate Pathway (PPP).
What does NADPH use NADPH for?
It uses their electrons to form superoxide radicals.
Where are superoxide radicals found and what is their purpose?
They are found inside the phagosome and they destroy the bacteria.
What does inducible NOS convert arginine into?
Citrulline and NO.
What is the purpose of NO?
To form peroxynitrite and NO to destroy bacteria.
In M1, the breakdown of TCA causes the accumulation of which intermediates?
Citrate and succinate.
What are the fates of citrate?
It is turned into Acetyl CoA for fatty acid synthesis.
Converted to oxaloacetate.
Which fatty acid might citrate become and what does it do?
It might become Prostaglandin E2 which mediates inflammation.
What is oxaloacetate used in?
Forming pryuvate via the NADPH producing malic enzyme.
In M1, IRG1 is upregulated to produce what?
Itaconate.
What is the purpose of itaconate?
To inhibit succinyl dehydrogenase
