# Identification of Some Glutamic Acid Derivatives with Biological Potential by Computational Methods
## 1 Introduction  
Throughout history, cancer has been a major health problem. It has been shown that there is a positive correlation between cancer incidence and age [1; 2; 3]. The individual risk of cancer is also influenced by family history, genetic susceptibility or behaviour, and exposure to carcinogenic factors [4]. Furthermore, the Krebs cycle and amino acids are proven to significantly affect cancer metabolism. Thus, interfering with amino acid metabolic pathways is an active area of study in cancer metabolism [5]. Amino acids are essential for cancer development because they can function as opportunistic fuel sources for cells [5]. Cancer cells use multiple strategies to obtain amino acids [6]. Higher-grade cancer cells must be able to supply additional metabolites for bioenergy and synthesise the necessary biosynthetic precursors of proteins, nucleic acids, and membrane lipids to grow substantially [7]. In cancer cells, glutamine is the major amino acid that serves as an anaplerosis metabolite and drives the tricarboxylic acid (TCA) cycle to sustain mitochondrial ATP for energy production [5]. Glutamine is the most abundant amino acid in plasma. The majority of circulating glutamine is produced in muscles and,Additionally, in the lungs [8]. However, it has been observed that a reduced exogenous supply of glutamine can impair malignant cells' survival or tumorigenic potential [6]. Glutamine is a versatile biosynthetic substrate for carbon and nitrogen atoms to generate important precursors for macromolecule biosynthesis [9]. It is the nitrogen donor for the biosynthesis of purines, pyrimidines, nicotinamide adenine dinucleotide, asparagine, and hexosamines via its terminal amide group. A higher expression of enzymes that mediate nucleotide synthesis from glutamine positively correlates with increased proliferation in tumours [10]. Glutamine also drives the uptake of essential amino acids, helps recycle excessive ammonia and glutamate, and activates the mammalian target of rapamycin (mTOR) that is involved in gene transcription and intracellular signalling [8; 9; 10]. In this regard, compounds that interfere with glutamine metabolism have shown therapeutic potential in preclinical studies by disrupting these growth-promoting processes [9]. In addition to providing building blocks for cell growth, glutamine metabolism plays a critical role in maintaining cellular redox homeostasis, as glutamate is a precursor for glutathione (GSH) [8; 11]. GSH is used to maintain redox homeostasis within the cell and to protect it from oxidative damage [12]. Because excessive free radicals lead to DNA damage, lipid peroxidation, and protein denaturation, tumour cells mitigate the excess of free radicals and maintain redox homeostasis principally by GSH synthesis [10]. In this regard, a process called glutaminolysis, catalysed by mitochondrial glutaminase, plays an essential role in the glutamine conversion to glutamate. Furthermore, it regulates reactive oxygen species homeostasis by providing the precursors glutamate and cysteine for GSH synthesis [13; 14]. Cancer cells rely on glutaminase activity to maintain a high ratio of glutamate to \(\alpha\)-ketoglutarate, which is essential for producing non-essential amino acids. This aspect explains glutamine's anaperiodic function [10]. Glutamate generates \(\alpha\)-ketoglutarate and fuels the TCA cycle through a transamination reaction. In the same way, transaminases, such as aspartate aminotransferase, facilitate the interconversion of aspartic acid. All these biochemical reactions maintain normal metabolism, allowing glutamate to be converted to other amino acids if necessary. Thus, this enzyme is considered to play an essential role in some types of cancer metabolism, such as in pancreatic cancer [5]. Glutamine synthetase (GS) is another critical enzyme involved in glutamine metabolism is because it converts glutamate to glutamine. This biochemical reaction is essential as glutamine is the body's non-toxic form of ammonia transport.