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

Stable Identifier
Reaction [transition]
Homo sapiens
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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, 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 RETRACTED: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
Catalyst Activity

fructose-2,6-bisphosphate 2-phosphatase activity of TIGAR [cytosol]

Orthologous Events
Cross References
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