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Implikasi Klinis Mutasi Gen Transketolase-Lke 1 pada Penyakit Kanker
Transketolase is an enzyme that catalyzes the conversion of aldose and ketose sugars in the pentose phosphate pathway. Up to now have been successfully identified three types of transketolase genes (TKT, TKTL 1, and TKTL 2) and a mutation (an iternal deletion) of transketolase-like gene 1 (TKTL 1). Mutations of the the TKTL1 gene will cause the loss of number of amino acid residues on the encoded proteins. Although TKTL1 proteins synthesized still have transketolase enzyme activity, but this mutant enzyme has different characteristics than the conventional transketolase enzyme. Changes in activity of this enzyme give clinical implications in cancer. In cancer, expression of TKTL1 gens is increased both at the mRNA or protein level . TKTL1 enzyme elevations are associated with changes in glucose metabolism in patient with cancer. In cancer cells, glucose will be broken down anaerobic into lactate via the pentose hosphate pathway although the oxygen is available. So the breakdown of glucose by TKTL 1 enzyme in cancer cells are oxygen-idenpendent (modified pentose-phosphate pathway) This alternative glucose metabolism is highly beneficial for carcinogenesis. So TKTL 1 enzyme plays an important role in tumor cell growth. Inhibition of this enzyme proved could suppress cancer cell proliferation. TKTL 1 can be a relevant target foe cancer therapeutic intervention.
A00002769 | Ebers Papyrus: 15(3): 161-168 | Available |
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