The role of pyruvate kinase in the diagnosis of hepatocellular carcinoma

Pyruvate kinase is a key enzyme in the glycolysis pathway, which can catalyze the conversion of phosphoenolpyruvate to enolpyruvate, and produce ATP, so it has an important physiological role. It has four isozymes, which are l, R, M1 and M2. It is high in kidney and malignant tumor cells. We can diagnose its role in hepatocellular carcinoma according to its characteristics.

1. The role of pyruvate kinase isoenzyme in the diagnosis of hepatocellular carcinoma

The activity of pyruvate kinase increased in patients with acute hepatitis, but decreased in patients with acute liver necrosis. M2 pyruvate kinase is not only subject to the fine regulation of tumor signal pathway, but also restricts the regulation of tumor signal pathway. They are closely related: M2 pyruvate kinase can regulate the activity of tumor related signal pathway and transcription factor, and its localization in cells is regulated by cancer related signal pathway.

2. Transcriptional regulation is involved in tumor metabolism

HIF-1 mainly plays a role in hypoxia and regulates the body's ability to adapt to hypoxia. Its main function is to induce hypoxia genes and restore the oxygen content of the intracellular environment. However, M2 pyruvate kinase can increase the transcription level of HIF-1, and there is a positive feedback regulation between HIF-1 and M2 pyruvate kinase. In addition, M2 pyruvate kinase can also be localized in the nucleus and participate in transcriptional regulation and post-translational modification of proteins.

3. Regulating tumor signaling pathway

Abnormal signaling pathways can lead to many diseases, especially in tumors. The regulation of M2 pyruvate kinase involved in glycolysis pathway on tumor related molecules is one of the current research hotspots.

4. Induce mitochondrial damage

Mitochondria is a kind of dynamic organelle with double membrane structure. The dynamic balance of mitosis and fusion, such as oxidative phosphorylation, glutamine metabolism and ATP synthesis, is carried out in mitochondria. The abnormal function of mitochondria breaks the normal state of life activity of cells, and can induce canceration in severe cases. Mitochondrial dysfunction induced by M2 pyruvate kinase was characterized by decreased ATP level, increased mitochondrial DNA copy number and increased mitochondrial fusion protein 2 (Mfn2). Knockdown of M2 pyruvate kinase could reduce the expression of Mfn2 protein, weaken M2 pyruvate kinase mediated mitochondrial fusion and restore mitochondrial function.