General amino acid metabolic machinery

The general amino acid metabolic machinery encompasses the integrated network of enzymes, transporters, and regulatory factors that govern the synthesis, interconversion, and degradation of amino acids. This system is fundamental to cellular life, providing the building blocks for protein synthesis, precursors for neurotransmitters and nucleotides, and carbon skeletons for energy production via the tricarboxylic acid cycle (StatPearls, 2023) [1]. It also plays a critical role in maintaining nitrogen balance and regulating cell signaling pathways, such as the mTOR pathway, which senses nutrient availability (Nature Reviews Molecular Cell Biology, 2017) [2]. In various pathologies, most notably cancer, the amino acid metabolic machinery is frequently hijacked to meet the increased biosynthetic and bioenergetic demands of malignant cells (Nature Reviews Cancer, 2020) [3]. Therapeutic interventions targeting this machinery include the use of enzymes to deplete circulating amino acids, small molecule inhibitors of specific metabolic enzymes, and antagonists of amino acid transporters, aiming to selectively starve diseased cells or correct metabolic imbalances (Signal Transduction and Targeted Therapy, 2022) [4]. Notable examples include L-asparaginase for leukemia and IDH inhibitors for various malignancies (PubMed, 2020) [5]. Sources: [1] https://www.ncbi.nlm.nih.gov/books/NBK557844/; [2] https://www.nature.com/articles/nrm.2017.83; [3] https://www.nature.com/articles/s41568-020-0281-4; [4] https://www.nature.com/articles/s41392-022-00969-x; [5] https://pubmed.ncbi.nlm.nih.gov/33067600/.

Other names

Amino acid metabolismAmino acid metabolic pathwaysCellular amino acid metabolic processProteostasis network

Depletion of specific essential amino acids, inhibition of rate-limiting metabolic enzymes, and blockade of amino acid transporters to disrupt cellular growth and survival.