Table 1.

Roles of Metabolites in Chromatin and Protein Modifications, Signal Transduction and Their Effects on Cancer

Metabolites	Roles in Modification or Signal Transduction	Effects on Cancer	References
1,3-BPG	pgK modification	Feedback regulation of glycolysis	[15]
	PGAM1 phosphorylation	Maintaining glycolytic flux and support cell growth	[16]
3-PG and 2-PG	Inhibiting PGD, activate PHGDH	Balancing the glycolysis and anabolic biosynthesis	[17]
PEP	Suppressing SERCA-Ca2+-NFAT signaling	Suppressing the antitumor function of T cells	[18,19]
Lactate	Inhibiting HDAC	Histone hyperacetylation and deregulating gene transcription	[33]
	Histone lactylation	Stimulating gene transcriptions	[34]
	PHD-mediate signaling	Angiogenic and proliferative effects	[22,24]
	Arg1/GPR81/MAVS signaling	Driving immune evasion	[25–30,32]
Ru-5-P and 6-PGL	Disrupting the LKB1-MO25-STRAD complex; Binding to Src and inhibiting PP2A activity	Regulating AMPK activity	[38,39]
2-HG Succinate Fumarate	Inhibiting TET/KDMs	DNA/histone hypermethylation	[53,54,56–60] [68–73] [68]
	Inhibiting PHD	Inhibiting HIF signaling and pseudohypoxia response	[61–63] [74,75] [73]
Succinate	Lysine succinylation	Maintaining the activity of multiple chromatin and metabolic enzymes	[76–78]
	SUCNR1-mediated signaling	Activating oncogenic signaling pathways, including ERK, STAT3, and PI3K/HIF-1α	[80,81]
Fumarate	Succination	Activating multiple glycolytic enzymes	[83–87]
Ac-CoA Acetate	Acetylation	Acetylation of histones and proteins, promoting tumorigenesis	[95–98,100,101] [104]
Acetate	GPR signaling	Preventing cancer cells from stress-induced damage	[106]
LCFA	FABP5 mediated signaling	SLCFA and ULCFA orchestrally regulate PPARβ/δ signaling	[107,108]
AA	Binding to BRAFV600E	Activation of MEK-ERK signaling and promoting tumor growth	[111–113]
3-OHB	Inhibiting Class I HDAC	Increasing histone acetylation	[118]
	Kbhb modification	Activating multiple oncogene promoters	[119,120]
	GPR109A signaling	Enhancing colonic cancer cells apoptosis and depressing survival	[121]
SAM	Methylation	Methylating numerous nucleic acids and histones	[123–127]
	Repressing β-catenin and IL-6 signaling	Reducing inflammation	[128,129]
GSH	S-glutathionylation	S-glutathionylation of proteins, protecting cancer cells from ROS attack	[133–135]
Kyn and KA	AhR signaling	Pro-carcinogenic effects	[139–143]
KA	Glutamate receptors	Promoting glioma cell proliferation	[145]

Abbreviations: 1,3-BPG, 1,3-bisphosphoglycerate; 3-PG, 3-phosphoglycerate; 2-PG, 2-phosphoglycerate; PEP, phosphoenolpyruvate; 6-PGL, 6-phosphogluconolactone; Ru-5-P, ribulose-5-phosphate; 2-HG, 2-hydroxyglutarate; Ac-CoA, Acetyl-CoA; LCFA, long chain fatty acid; AA, acetoacetate; 3-OHB, 3-hydroxybutyrate; SAM, S-adenosyl-methionine; GSH, glutathione; Kyn, kynurenine; KA, kynurenic acid.