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. Author manuscript; available in PMC: 2022 Aug 1.
Published in final edited form as: Trends Cancer. 2021 May 18;7(8):790–804. doi: 10.1016/j.trecan.2021.04.003

Figure 1. Glutamine metabolism in quiescent and proliferating cells.

Figure 1.

Proliferative metabolism is characterized by a broad upregulation of biosynthetic pathways. Glutamine is acquired either through uptake transporters such as SLC1A5 or, in nutrient-poor microenvironments, from extracellular protein via macropinocytosis followed by lysosomal degradation. Glutamine is an obligate nitrogen donor for nucleotide and asparagine biosynthesis and an exchange factor for some less abundant amino acids. Its catabolite glutamate is a precursor of α-KG for TCA cycle anaplerosis, a substrate for glutathione biosynthesis, a carbon and nitrogen source for NEAA biosynthesis, and also an exchange factor for other amino acids. Blue arrows indicate pathways in which glutamine/glutamate serve as a nitrogen source, green arrows indicate use of glutamine-derived carbon for anaplerosis, orange arrows represent direct incorporation of glutamate into biosynthetic pathways, and yellow arrows show exchange factor functions.

Abbreviations: α-KG, α-ketoglutarate; Ala, alanine, Asp, aspartate; Cys, cystine or cysteine; GCL, glutamate-cysteine ligase; GGC, γ-glutamylcysteine; Gln, glutamine; Glu, glutamate; GLS, glutaminase; GLS2, glutaminase 2; GLUD1, glutamate dehydrogenase 1; Gly, glycine; GOT2, mitochondrial aspartate aminotransferase; GPT2, mitochondrial alanine transaminase; GS, glutathione synthetase; GSH, reduced glutathione; NEAA, non-essential amino acids; OAA, oxaloacetate; PRPP, 5-phosphoribosyl-1-pyrophosphate; P-Ser, phosphoserine; Pyr, pyruvate; Ser, serine; SLC1A5 var, SLC1A5 variant; TCA, tricarboxylic acid.