Table 1.

Signalling immunometabolites and their properties

Metabolite	Main pathway(s)	Immune cell behaviour impacted	Abundance regulation (key enzymes)	Abundance regulation (nutrient flux)	Intracellular signalling mechanism	Intracellular targets	Extracellular signalling mechanism
Succinate	TCA cycle	Macrophages, T cells	SDH/CII activity	Glutamine anaplerosis	Product inhibition	PHDs, α-KGDDs	Receptor agonist (SUCNR1/GPR91)
Fumarate	TCA cycle	Macrophages, DCs, T cells	FH suppression, ASS1 increase	Glutamine anaplerosis	Product inhibition, PTM (succination)	PHDs, α-KGDDs + many	N/A
Itaconate	TCA cycle-derived	Macrophages, neutrophils, MDSCs, T cells	IRG1/ACOD1 increase	Glucose, glutamine anaplerosis	Product inhibition, PTM (2,3-dicarboxypropylation), Allostery*	SDH/CII, PHDs, α-KGDDs + many	Receptor agonist (OXGR1)
α-KG	TCA cycle	Macrophages	OGDH, IDH, GOT1/2 activity	Glutamine anaplerosis	Substrate provision	PHDs, α-KGDDs	N/A
L-2-HG	TCA cycle-derived, glycolysis	Macrophages, T cells	IDH, MDH, LDH (promiscuous activity), L2HGDH	Glutamine anaplerosis	Product inhibition, competitive inhibition	PHDs, α-KGDDs	N/A
D-2-HG	TCA cycle-derived	Macrophages, T cells	IDH, (neomorphic activity), HOT, D2HGDH	Glutamine anaplerosis	Product inhibition	PHDs, α-KGDDs, LDH	N/A
Lactate	Glycolysis	Macrophages, T cells	LDH, activity	Glucose, pyruvate, lactate uptake	Allostery, PTM (lactoylation), acidification	Histones, NDRG3, MAVS, SENP1	Receptor agonist (GPR81)
MGO	Glycolysis	Macrophages	GLO1, GLO2	Glucose, aminoacetone	PTM (glycation), Metabolite modification	Many, arginine depletion	N/A
LGSH	Glycolysis	Macrophages	GLO1, GLO2	Glucose	PTM (lactoylation)	Histones	N/A
KYN	Tryptophan catabolism, NAD+ synthesis	Monocytes, macrophages	IDO1	Tryptophan uptake	Ligand	AhR	N/A
KYNA	Tryptophan catabolism, NAD+ synthesis	Monocytes, macrophages	IDO1, KAT	Tryptophan uptake	Ligand	AhR	Receptor agonist (GPR35), receptor antagonist (NMDA etc)

PTM, post-translational modification.