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Glutamate dehydrogenase is so important for tumor and cancer screening
The CAS number of glutamate dehydrogenase (GDH) is 9029-12-3. It is a mitochondrial enzyme that is commonly found in animals, plants and microorganisms. It belongs to the superfamily of amino acid dehydrogenases. Play a key role in the metabolic process. Under normal circumstances, the enzyme uses NAD+ and/or NADP+ as coenzymes to catalyze the reversible oxidative deamination of L-glutamic acid to generate ɑ-ketoglutarate, thereby participating in the tricarboxylic acid cycle (TCA cycle), signal transduction, nitrogen and Regulation of carbon metabolism and other physiological activities. It plays an important role in energy regulation and maintaining cell homeostasis.
Many studies have shown that although glutamine can be synthesized in most tissues, its demand often exceeds the supply. Glutamine is usually an essential nutrient for cell proliferation [. More and more studies have shown that glutamine metabolism plays an important role in tumor growth, proliferation and metastasis. In many cancer cells, glutamine is the main mitochondrial substrate, and glutamate dehydrogenase is glutamine. One of the key enzymes in the metabolic pathway, so glutamate dehydrogenase is also very important for tumor cells.
Studies have found that human breast cancer cells mainly use glutamate dehydrogenase to catalyze reducing amine to assimilate ammonia, thereby accelerating the proliferation of breast cancer cells. Through experiments, Ryu et al. found that the expression of glutamate dehydrogenase in canine breast tumor cells also increased to a certain extent. Therefore, specifically inhibiting the expression level and activity of glutamate dehydrogenase in breast cancer cells may have the potential to inhibit the proliferation and spread of breast cancer cells.
In patients with liver disease, the activity of glutamate dehydrogenase in liver cancer cells is significantly lower than that in adjacent normal liver cells or cirrhotic liver cells. In addition, the overall glutamate dehydrogenase activity of all tumor cells Enzyme activity is lower than 30% of normal and cirrhotic liver cell activity. After hepatocyte necrosis and mitochondrial disintegration, GDH will escape the cells and enter the blood. The increase of plasma GDH in patients with liver cancer is the most obvious. Therefore, the determination of serum GDH activity and content can be used as an indicator for the diagnosis of mitochondrial damage and hepatocellular disease .
Colorectal cancer is the third most common new type of cancer, and its mortality rate is also ranked third among cancers. It is one of the cancers with a higher mortality rate. According to related reports, the 5-year survival rate of patients diagnosed with local colorectal cancer is 90%, which drops to 68% after local spread, and drops sharply to 10% after long-distance spread. Liu et al. found that the expression level of GDH in colorectal cancer cells is higher than that of the corresponding non-tumor cells. The overexpression of GDH is related to the migration ability and tumor size of colorectal cancer. The higher the expression level of GDH, the stronger the tumor migration ability. The larger the size, when shRNA is used to inhibit the gene encoding GDH, the proliferation and migration ability of colorectal cancer cells will be significantly reduced.
It can be seen that enzyme preparation glutamate dehydrogenase is very important for tumor and cancer detection. More and more evidences show that GDH is closely related to tumor cell proliferation, migration, invasion and other activities. There is an abnormal rise in expression. GDH has gradually become a potential target for cancer treatment, and the screening of GDH inhibitors may gradually become a research hotspot.