Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy

Table 2 Potential enzymes targets for cancer stem cell therapy, role in metabolism, treatment strategy in cancer stem cell-based therapy

Enzyme	Role in amino acid metabolism	CSC therapy
MTase	Translates homocysteine to methionine	Inhibition
MATα2	Induces the production of SAM	Inhibition
IDO1	Catalyzes tryptophan into kynurenine	Inhibition
TDO2	Catalyzes tryptophan into kynurenine	Inhibition
GLDC	Catalyzes glycine into NH3, CO2 and CH2-THF	Inhibition (except gastric cancer, better inhibit SHMT and GCAT simultaneously)
PHGDH	Catalyzes 3P-glycerate into 3-P-OH-pyruvate	Inhibition
SHMT1/2	Completes the conversion between serine and glycine	Inhibition
GLS1	Catalyzes glutamine into glutamate	Inhibition
GDH	Catalyzes glutamate into α-KG	Inhibition
CBS	Translates homocysteine to cystathionine	Inhibition
CGL	Catalyzes cystathionine to cysteine	Inhibition
GCL	Catalyzes the production of γ-glutamyl-cysteine	Inhibition
GSS	Catalyzes GSH production	Inhibition
GOT1	Catalyzes the production of oxaloacetate from aspartate	Inhibition
GPT2	Catalyzes transamination between alanine and α-KG to pyruvate and glutamate	Inhibition
PRODH	Oxidize proline to glutamate	Inhibition

CSC: Cancer stem cell; MTase: Methyltransferase; MAT: Methionine adenosyltransferase; SAM: S-adenosine methionine; IDO1: Indoleamine-2,3-dioxygenase-1; TDO2: Tryptophan 2,3-dioxygenase; GLDC: Glycine decarboxylase; 1C-THF: One-canton tetrahydrofolate; PHGDH: Phosphoglycerate dehydrogenase; SHMT: Serine hydroxymethyl transferase; GCAT: Glycine C-acetyltransferase; GLS: Glutaminase; GDH: Glutamate dehydrogenase; α-KG: α-ketoglutarate; CBS: Cystathionine β synthase; CGL: Cystathionine γ lyase; GCL: Glutamate cysteine ligase; GSS: Glutathione synthetase; GSH: Glutathione; GOT: Aspartate aminotransferase; GPT2: Glutamic pyruvate transaminase; PRODH: Proline dehydrogenase.