Reactome | PFKFKB dimer phosphorylates Fru(6)P

PFKFKB dimer phosphorylates Fru(6)P

Stable Identifier

R-HSA-71802

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

D-fructose 6-phosphate + ATP => D-fructose 2,6-bisphosphate + ADP, Fructose 6-phosphate and ATP react to form fructose 2,6-bisphosphate and ADP

ReviewStatus

5/5

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The 6-phosphofructo-2-kinase activity of cytosolic PFKFB (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase) homodimer catalyzes the reaction of fructose 6-phosphate and ATP to form fructose 2,6-bisphosphate and ADP (Pilkis et al. 1988). Fructose 2,6-bisphosphate is not itself on the pathway of glycolysis. Rather, it acts as a positive allosteric effector of phosphofructokinase 1, greatly increasing the rate of synthesis of fructose 1,6-bisphosphate and hence the overall rate of glycolysis. The conversion of PFKFB between its dephosphorylated form, which catalyzes the synthesis of fructose 2,6-bisphosphate as described here, and its phosphorylated form, which catalyzes the hydrolysis of fructose 2,6-bisphosphate to fructose 6-phosphate and orthophosphate plays a central role in the short-term regulation of glycolysis (Pilkis et al. 1995).

Four isoforms of PFKFB protein encoded by four different genes exhibit tissue-specific expression patterns. PFKFB1 is expressed in the liver (Algaier and Uyeda 1988), PFKFB2 is expressed in the heart (Hirata et al. 1998), PFKFB3 is ubiquitously expressed (Manes and el-Maghrabi 2005), and PFKFB4, originally described as a testis-specific gene product (Manzano et al. 1999), may also be expressed in several kinds of tumors.

Literature References

PubMed ID	Title	Journal	Year
10095107	Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene Manzano, A, Perez, JX, Nadal, M, Estivill, X, Lange, A, Bartrons, R	Gene	1999
15896703	The kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is regulated via inhibition by phosphoenolpyruvate Manes, NP, el-Maghrabi, MR	Arch Biochem Biophys	2005
9464277	Expression of human placental-type 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in various cells and cell lines Hirata, T, Kato, M, Okamura, N, Fukasawa, M, Sakakibara, R	Biochem Biophys Res Commun	1998
3052289	Hormonal regulation of hepatic gluconeogenesis and glycolysis Pilkis, SJ, el-Maghrabi, MR, Claus, TH	Annu Rev Biochem	1988
2837207	Molecular cloning, sequence analysis, and expression of a human liver cDNA coding for fructose-6-P,2-kinase:fructose-2,6-bisphosphatase Algaier, J, Uyeda, K	Biochem Biophys Res Commun	1988
7574501	6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme. Pilkis, SJ, Claus, TH, Kurland, IJ, Lange, AJ	Annu Rev Biochem	1995