Table 1.

An overview of metabolic fate of glutamine across different cancers.

Pathway	Involved Molecules	Cancer Type	Study Type	References
Increased glutamine transport	SLC1A5	Lung cancer	Clinical and in vitro	[63]
		Breast cancer (TNBC)	In vitro and in vivo	[64]
		Head and neck cancer	In vitro and in vivo	[65]
		Colorectal cancer	In vitro and in vivo	[66,67]
	SLC6A14	Pancreatic cancer	Clinical, in vitro, and in vivo	[68]
	SLC38A5	Breast cancer (TNBC)	Clinical, in vitro, and in vivo	[69]
		Pancreatic cancer	Clinical and in vivo	[70]
Increased glutamine/arginine transport	SLC6A14	Cervical cancer	Clinical	[71]
		Colorectal cancer	Clinical	[72]
		Breast cancer (ER+)	In vitro and in vivo	[73]
Increased glutamine efflux	SLC7A5	Colorectal cancer (K-Ras mutation)	In vivo	[74]
Increased glutaminolysis	GLS1	Breast cancer	Clinical, in vitro, and in vivo	[75,76,77]
		Prostate cancer	Clinical and in vitro	[78,79,80]
		Colorectal cancer	Clinical, in vitro, and in vivo	[81]
		Lung cancer	Clinical, in vitro, and in vivo	[82]
Increased glutaminolysis	GLS2	Pancreatic cancer	In vivo	[83]
Controls glutamine metabolism and ROS level	GLS2 *	Hepatocellular cancer	In vitro	[84,85]
Glutamine contributes to antioxidative capacity of cancer cell	GCL	Breast cancer	In vitro and in vivo	[86]
		Lung cancer	In vitro and in vivo	[87]
		Liver cancer	In vivo	[88]
	GDH1	Lung cancer	In vitro and in vivo	[89]
		Breast cancer	In vitro and in vivo	[90]
	GOT1/GOT2	Pancreatic cancer	In vitro and in vivo	[91]
	GOT2	Pancreatic cancer	In vitro	[92]
Glutamine contributes to citrate and lipid synthesis through reductive carboxylation (RC) of α-ketoglutarate (αKG) as well as contributing to aspartate and pyrimidine synthesis	IDH2	Renal cell carcinoma deficient in the von Hippel–Lindau (VHL) tumor suppressor gene	In vitro and in vivo	[93]
		Renal cell carcinoma and glioblastoma	In vitro	[94]
Glutamine oxidation maintains TCA cycle	GDH1	Lung cancer	In vitro and in vivo	[95]
		Glioblastoma	In vitro	[96]
Glutamine contributes to de novo nucleotide synthesis	GMPS	Prostate cancer	Clinical and in vitro	[97]
	GLS1, PPAT, and their ratio PPAT/GLS1	Lung cancer/potential role in other cancers	In vitro and in vivo	[98]
	PPAT and PAICS	Lung cancer	Clinical, in vitro, and in ovo	[99]
	NA	Breast cancer with SIRT3 loss	In vitro and in vivo	[100]
Glutamine contributes to de novo asparagine synthesis	ASNS	Different cancer cell lines	In vitro	[101]
		Lung cancer	Clinical and in vitro	[102]
Glutamine synthesis	GLUL	Pancreatic cancer	Clinical, in vitro, and in vivo	[103,104]
		Glioblastoma	Clinical, in vitro, and in vivo	[105]

The key metabolic enzymes contributing to Gln metabolism: SLC1A5, neutral amino acid transporter belonging to the solute carrier (SLC) family 1 member 5; SLC6A14, neutral and basic amino acid transporter belonging to SLC family 6 member 14; SLC38A5, neutral amino acid transporter belonging to SLC family 38 member 5; SLC7A5, essential amino acid transporter, neutral amino acid antiporter belonging to SLC family 7 member 5; GLS1, glutaminase (characterized as kidney (also known as brain)-type); GLS2, glutaminase (characterized as liver-type); GCL, glutamate cysteine ligase; GDH1, glutamate dehydrogenase 1; GOT1, glutamate oxaloacetate transaminase 1 (cytosolic); GOT2, glutamate oxaloacetate transaminase 2 (mitochondrial); IDH2, isocitrate dehydrogenase 2 (mitochondrial); GMPS, guanosine monophosphate synthetase; PPAT, phosphoribosyl pyrophosphate amidotransferase; PAICS, phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase; ASNS, asparagine synthetase; GLUL, glutamate ammonia ligase (also known as glutamine synthase). Other abbreviations: ROS, reactive oxygen species; TCA, tricarboxylic acid; TNBC, triple-negative breast cancer; ER⁺, estrogen-receptor-positive; K-Ras, Kirsten rat sarcoma virus. SIRT3, sirtuin 3 (mitochondrial). “*” reflects decreased expression of GLS2 supporting growth of hepatocellular cancer.