Question

Answer all of the following about glucose catabolism in cancer tissues compared to normal tissues:
What enzymes of glucose metabolism are expressed in higher levels in cancer tissues than normal tissues? Give at least three specific examples and include explanations of the benefits of these enzymes being expressed in higher levels. If specific isoforms have been identified, associated with specific cancers, also include that information.

Answer 1

Hexokinase 2 (HK2) gets active in glucose metabolism while it has been seen that the enzyme is higher in percentage in the cancerous cell as compared to the normal cell.

Benefits of this enzymes :

1.Hexokinase or D-hexose 6-phosphotransferase is the most important enzyme which involves catalyzes the initial step of the glycolysis pathway of the cell. Enzyme actually transfers a phosphate from ATP to glucose which then produces glucose-6-phosphate. This enzyme actually found in 4 isoforms the HK 2 is mostly found in skeletal muscle and in the heart. The higher level of this found in cancerous cells.

It is found that there is an interaction of HK1 AND HK 2 with VDAC i.e.voltage-dependent anion channel, and these two isoforms of HK are capable to bind with the mitochondria. The association plays an important role in mitochondrial homeostasis. Further on such kind of a mitochondrial association influence the HK enzyme kinetics.

2.HK involves in high glycolytic activity in the cancerous cells. The study has shown that the HK percentage binding to the mitochondria is raised as compared to the normal cell. Take an example of AS-20D liver tumor cells, the protein level of HK, that is mainly HKII > 500 times higher than as present in the liver cells normally. And now 80% of HKII is attached to the mitochondria of the tumor cell. This up-regulation of HKII in malignant cancerous cells and in the glycolytic pathway, This is all responsible to make HK as an anticancer drug development target which then plays a major role to eradicate cancer.

3. A cancerous cell completely depends on glycolysis that is to generate ATP and comprises some actively use certain glycolytic metabolic intermediates.HKII is the most reliable glycolytic enzyme which regulates apoptotic cell death which is initiated by the mitochondria .3-bromopyruvate (3-BrPA) is an effective inhibitor of HKII . This 3-BrPA is actually found to be effective for an inhibition of metabolism of cancer cell further inhibition of tumor cell metabolism leads to cell death. The basic reason behind that is dissociation of HK2 from mitochondria which is done by 3-BrPA which actually causes a covalent modification of HKII protein.