Immunometabolism

Question 1

What is the function of an M2 macrophage?

Answer 1

It is important to keep homeostasis and for anti-inflammatory reactions. It is important in tissue repair and wound healing.

Question 2

What is the function of an M1 macrophage?

Answer 2

Bacterial killing, killing tumor cells, and pro-inflammatory reactions.

Question 3

What metabolic processes are characteristic of M2 macrophages?

Answer 3

High Ox-Phos, sustained ATP and long-lived cells

Question 4

What metabolic processes are characteristic of M1?

Answer 4

Glycolysis and PPP
Biosynthesis / anabolism
Fast ATP
Short life

Question 5

What metabolic processes are characteristic of M1?

Answer 5

Glycolysis and PPP
Biosynthesis/anabolism
Fast ATP
Short life

Question 6

What is catabolism?

Answer 6

The breakdown of molecules for the creation of energy

Question 7

What is anabolism?

Answer 7

The formation of molecules to store energy

Question 8

What enzyme regulates the production of inflammatory cytokines in M1 macrophages?

Answer 8

GAPDH - it raises the rate of glycolysis and production of IL-1b and TNFa

Question 9

In what ways does succinate drive inflammation?

Answer 9

1. It induces IL-1b production through HIF-1a
2. Succinate dehydrogenase repurposes mitochondria to drive inflammation
3. Succinate is picked up by macrophages, leading to an inflammatory metabolic state

Question 10

How does itaconate lead to an anti-inflammatory reaction?

Answer 10

Itaconate stops the production of succinate by inhibiting succinate dehydrogenase.

Question 11

What are the six main pathways involved in immune metabolism?

Answer 11

1. PPP (pentose phosphate pathway)
2. Fatty Acid Oxidation
3. Fatty Acid Synthesis
4. TCA (tricarboxylic acid) cycle
5. Glycolysis
6. Amino Acid Metabolism

Question 12

What gene is the central metabolic regulator of immunity?

Answer 12

mTOR.

Question 13

What is the function of mTOR?

Answer 13

Can sense amino acids and growth factors and promote mRNA translation and lipid synthesis, in support of cell growth.

It also regulates numerous events that are crucial for T-cell and monocyte differentiation.

Question 14

What does AMP kinase do in terms of metabolism and immunity?

Answer 14

Inhibits the function of mTOR and promotes catabolism. It is mostly active during nutrient deprivation.

Question 15

What is the role of glycolysis in (immune) metabolism?

Answer 15

Glycolysis by itself has a low ATP generation potential, but it gives rise to many important metabolites and co-factors used for other metabolic pathways, like PPP and amino acid synthesis. This pathway is very active in rapidly proliferating cells.
Its main products are NADH and NAD+.

Question 16

What is the role of the TCA cycle in (immune) metabolism?

Answer 16

It is the pathway most used in non-proliferative cells. Its goal is to produce ATP. These are used for long-lived cells. It is also used for amino acid and fatty acid synthesis.

Question 17

What is cataplerosis?

Answer 17

Diversion of TCA intermediates into a metabolic process (e.g. FAS)

Question 18

What is anaplerosis?

Answer 18

Diversion of TCA intermediates to the TCA cycle. Used to feed those in another pathway.