The metabolism of glutamine and glutamate, two important amino acids, has been implicated in the development and progression of feline mammary cancer, a malignant neoplasm that occurs in the mammary glands of cats. These amino acids play critical roles in various cellular processes, including protein synthesis, energy production, and redox balance, and dysregulation of their metabolism has been associated with cancer-related pathways in several cancers, including mammary cancer in cats. Glutamine is a non-essential amino acid that serves as a major source of nitrogen and carbon for cancer cells. It can be converted into α-ketoglutarate, an intermediate in the citric acid cycle, through the action of glutaminase enzyme. α-ketoglutarate can then be utilized in the biosynthesis of nucleotides, which are essential for DNA synthesis and cell division. Dysregulation of Glutamine metabolism has been shown to impact cellular energy production, redox balance, and nucleotide synthesis, all of which are critical for cancer cell growth and survival. Similarly, glutamate, another non-essential amino acid, plays a key role in cancer metabolism. It can be converted into α-ketoglutarate through the action of amino acid oxidase enzyme, which generates hydrogen peroxide as a byproduct. Hydrogen peroxide is a reactive oxygen species (ROS) that can cause oxidative stress and damage to cellular components, including DNA, proteins, and lipids. Dysregulation of glutamate metabolism and the accumulation of ROS have been linked to DNA damage, genomic instability, and tumor progression in various cancers. Furthermore, alterations in the metabolism of glutamine and glutamate may also impact the tumor microenvironment and immune response in feline mammary cancer. For instance, changes in the levels of glutamine and glutamate have been detected in the blood and tissue samples of cats with mammary cancer, suggesting that these amino acids may serve as potential biomarkers for early detection and prognosis of feline mammary cancer. Additionally, the metabolism of glutamine and glutamate has been shown to modulate the activity of immune cells in the tumor microenvironment, potentially influencing the immune response against cancer cells. 1