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PKM2 plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isoforms, catalyzes the last energy-generating step in glycolysis, but is unique in its capacity to be regulated. PKM2 is regulated on several cellular levels, including gene expression, alternative splicing and post-translational ...
Phosphorylation of PKM2 by Mitogen-activated protein kinase 1 (ERK2) causes conformational changes that allow PKM2 to enter the nucleus and regulate glycolytic gene expression required for tumor development. [39] Some studies state that there is a shift in expression from PKM1 to PKM2 during carcinogenesis.
Tumor M2-PK is a synonym for the dimeric form of the pyruvate kinase isoenzyme type M2 (), a key enzyme within tumor metabolism.Tumor M2-PK can be elevated in many tumor types, rather than being an organ-specific tumor marker such as PSA.
In this way, the advantage conferred by PKM2 expression would be eliminated. In preclinical studies, drugs such as 6-amino-nicotinamide (6-AN), which inhibits G6P dehydrogenase, the enzyme that initiates the PPP have shown anti-tumorigenic effects in leukemia , glioblastoma and lung cancer cell lines.
PKM2 is an isozyme of pyruvate kinase that is responsible for the Warburg effect in cancer cells. [12] A-Raf upregulates the activity of PKM2 by promoting a conformational change in PKM2. This causes PKM2 to transition from its low-activity dimeric form to a highly active tetrameric form.
In oncology, the Warburg effect (/ ˈ v ɑːr b ʊər ɡ /) is the observation that most cancers use aerobic glycolysis and lactic acid fermentation for energy generation rather than the mechanisms used by non-cancerous cells. [1]
Cumulus cells aid in oocyte development and show higher expression of SLC38A3, a transporter for amino acids, and Aldoa, Eno1, Ldh1, Pfkp, Pkm2, and Tpi1, enzymes responsible for glycolysis. [7] MGCs are more steroidogenically active and have higher levels of mRNA expression of steroidogenic enzymes such as cytochrome P450. [ 8 ]
Hexokinase ATP ADP Glucose 6-phosphate Glucose-6-phosphate isomerase Fructose 6-phosphate Phosphofructokinase-1 ATP ADP Fructose 1,6-bisphosphate Fructose-bisphosphate aldolase Dihydroxyacetone phosphate + + Glyceraldehyde 3-phosphate Triosephosphate isomerase 2 × Glyceraldehyde 3-phosphate 2 × Glyceraldehyde-3-phosphate dehydrogenase NAD + + P i NADH + H + NAD + + P i NADH + H + 2 × 1,3 ...