My enzymology of cancerous cell. Glycolysis is

My specific area of interest is on enzymology of cancerous cell. Glycolysis is an almost universal central pathway of glucose catabolism. The glycolytic breakdown of glucose is the sole of metabolic energy in animal tissue, plant tissue and many anaerobic microorganisms or also totally dependent on glycolysis.

Almost 12 enzymes which catalyze steps in the Embden-Meyerhof glycolytic pathway like as hexokinase, phosphohexose isomerase, aldolase, pyruvate kinase, lactate dehydrogenase, phosphofructokinase etc. Phosphofructokinase is the first key regulation point of glycolysis and first major committed step that cannot go back. This enzyme is inactive when ATP level is high in the cell. By mutation this feedback is blocked and those cells which are capable of increasing glycolysis sufficiently for survival eventually become cancer cell. In many types of tumors found in humans and other animals, glucose uptake and glycolysis proceed about 10 times faster than in normal cell.

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Most tumor cells grow under hypoxic condition because at least initially they lack the capillary network to suplly sufficient oxygen. Cancer cell located more then 100–200 micrometer from the nearest capillaries must dependent on glycolysis alone for much of their ATP production. It is likely that two early steps in the transformation of a normal cell into a tumor cell are (1) the change to dependence on glycolysis for ATP production and (2) the development of tolerance to a low pH in the extracellular fluid.

In general, the more aggressive the tumor, the greater is its rate of glycolysis. The heavier reliance of tumors then of normal tissue on glycolysis suggests a possibility for anticancer therapy; inhinbitors of glycolysis might target and kill tumor by depleting their supply of ATP. Three inhibitors of hexokinase as chemotherapeutic agents;  (1)  2-deoxyglucose, (2)  Iodinamine,  (3)  3-bromo pyruvate. By preventing the formation of glucose-6-phosphate, these compounds not only deprive tumor cells of glycolytically produced ATP but also prevent the formation of pentose phosphates via the pentose phosphate pathway which also begins with glucose-6-phosphate.



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