Amino acids in cancer

Abstract

Over 90 years ago, Otto Warburg's seminal discovery of aerobic glycolysis established metabolic reprogramming as one of the first distinguishing characteristics of cancer 1. The field of cancer metabolism subsequently revealed additional metabolic alterations in cancer by focusing on central carbon metabolism, including the citric acid cycle and pentose phosphate pathway. Recent reports have, however, uncovered substantial non-carbon metabolism contributions to cancer cell viability and growth. Amino acids, nutrients vital to the survival of all cell types, experience reprogrammed metabolism in cancer. This review outlines the diverse roles of amino acids within the tumor and in the tumor microenvironment. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, amino acid derivatives contribute to epigenetic regulation and immune responses linked to tumorigenesis and metastasis. Furthermore, in discussing the transporters and transaminases that mediate amino acid uptake and synthesis, we identify potential metabolic liabilities as targets for therapeutic intervention.

Association between Metabolites and the Risk of Lung Cancer: A Systematic Literature Review and Meta-Analysis of Observational Studies

“…The influential roles of methionine in cancer cell growth has been well-documented [ 96 , 97 , 98 , 99 ]. Methionine is involved in several critical activities in cancer cells, such as nucleotide biosynthesis via the one-carbon metabolism pathway [ 100 , 101 , 102 ] and protein synthesis [ 103 ]. Methionine is also a precursor metabolite of S-adenosylmethionine, a co-substrate involved in methyl group donation, for cellular processes such as epigenetic control and protein methylation [ 100 , 104 , 105 ].…”

“…Methionine is involved in several critical activities in cancer cells, such as nucleotide biosynthesis via the one-carbon metabolism pathway [ 100 , 101 , 102 ] and protein synthesis [ 103 ]. Methionine is also a precursor metabolite of S-adenosylmethionine, a co-substrate involved in methyl group donation, for cellular processes such as epigenetic control and protein methylation [ 100 , 104 , 105 ]. Previous reviews have identified that the DNA methylation patterns in lung cancer were altered, where genome-wide hypomethylation, and hypermethylation of the promoter regions of several tumor suppressor genes, such as DAPK , RASSF1A and RARβ , were commonly observed [ 106 , 107 ].…”

“…Folate is a metabolite in the folate cycle, which is part of the one-carbon metabolism pathway [ 100 , 101 , 102 ]. Folate is coupled with the methionine cycle as one of its metabolites, 5-methyltetrahydrofolate, is involved in the regeneration of methionine from homocysteine [ 100 , 101 , 102 ]. Similar to methionine, folate is involved in nucleotide biosynthesis.…”

“…Similar to methionine, folate is involved in nucleotide biosynthesis. 10-formyltetrahydrofolate, a metabolite in the folate cycle, serves as a formyl group donor for the formation of carbon-2 and carbon-8 of the purine ring in de novo purine synthesis [ 100 , 101 , 102 ].…”

The Interplay Between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression in Vitro and in Vivo

“…This could explain the activated OxPhos metabolism that we have found in the RT4 cells, which determines a higher consumption of glutamine, BCAAs and serine. Both glutamine and BCAAs can act as anaplerosis metabolites driving the TCA cycle through the generation of alpha-ketoglutarate [23] and acetyl-CoA, respectively [24]. Likewise, the increased uptake and catabolism of serine, with higher excretion of formate and glycine, is related to a higher mitochondrial activity.…”