Reactome | TIGAR converts D-fructose-2,6-bisphosphate to D-fructose 6-phosphate

TIGAR converts D-fructose-2,6-bisphosphate to D-fructose 6-phosphate

Stable Identifier

R-HSA-5628905

Type

Reaction

Species

Homo sapiens

Compartment

cytosol

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TIGAR converts D-fructose-2,6-bisphosphate to D-fructose 6-phosphate

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TIGAR shares similarity with PGMs (phosphoglycerate mutases), especially PFK2 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase). TIGAR possesses only the bisphosphatase domain and converts D-fructose 2,6-bisphosphate into D-fructose 6-phosphate (Bensaad et al. 2006). Reduction of fructose 2,6-bisphosphate levels correlates with decrease in glycolytic rates, which makes cells more sensitive to apoptotic stimuli (Vander Heiden et al. 2001). Alternatively, fructose 6-phosphate can be isomerized to glucose 6-phosphate, which is diverted to the pentose phosphate pathway, which can have an anti-apoptotic effect (Boada et al. 2000, Perez et al. 2000). In the pentose phosphate pathway, oxidized glutathione is reduced, and this reduced glutathione can then be used by glutathione peroxidase to remove hydrogen peroxide, thereby protecting cells from the oxidative stress (Kletzien et al. 1994, Fico et al. 2004, Tian et al. 1999). Indeed, expression of TIGAR increases reduced glutathione to oxidized glutathione ratio and lowers ROS (reactive oxygen species) levels in cells (Bensaad et al. 2006, Lee et al. 2014).

Literature References

PubMed ID	Title	Journal	Year
10329961	Importance of glucose-6-phosphate dehydrogenase activity in cell death Braunstein, LD, Apse, K, Stanton, RC, Pang, J, Rose, M, Tian, X, Tian, WN	Am. J. Physiol.	1999
8119488	Glucose-6-phosphate dehydrogenase: a "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress Kletzien, RF, Harris, PK, Foellmi, LA	FASEB J.	1994
11486029	Growth factors can influence cell growth and survival through effects on glucose metabolism Harris, MH, Plas, DR, Vander Heiden, MG, Thompson, CB, Fox, CJ, Rathmell, JC	Mol. Cell. Biol.	2001
16839880	TIGAR, a p53-inducible regulator of glycolysis and apoptosis Vidal, MN, Bensaad, K, Selak, MA, Tsuruta, A, Nakano, K, Gottlieb, E, Bartrons, R, Vousden, KH	Cell	2006
15044966	Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stress-induced apoptosis Iaccarino, I, Cigliano, L, Martini, G, Filosa, S, Fico, A, Verde, P, Abrescia, P, Paglialunga, F	Cell Death Differ.	2004
11029283	Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progression Bermudez, J, Dalmau, M, Bartrons, R, Rosa, JL, Ventura, F, Manzano, A, Boada, J, Perez, JX, Roig, T	Am. J. Physiol., Cell Physiol.	2000
11034341	Cells overexpressing fructose-2,6-bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress Cascante, M, Bartrons, R, Bermúdez, J, Gámez, A, Perez, X, Boada, J, Roig, T	FEBS Lett.	2000
24383451	TIGAR, TIGAR, burning bright Cheung, EC, Vousden, KH, Lee, P	Cancer Metab	2014