Xylulose 5-phosphate explained

D-Xylulose 5-phosphate (D-xylulose-5-P) is an intermediate in the pentose phosphate pathway. It is a ketose sugar formed from ribulose-5-phosphate by ribulose-5-phosphate epimerase. In the non-oxidative branch of the pentose phosphate pathway, xylulose-5-phosphate acts as a donor of two-carbon ketone groups in transketolase reactions.^[1]

Xylulose-5-phosphate also plays a crucial role in the regulation of glycolysis through its interaction with the bifunctional enzyme PFK2/FBPase2. Specifically, it activates protein phosphatase, which then dephosphorylates PFK2/FBPase2. This inactivates the FBPase2 activity of the bifunctional enzyme and activates its PFK2 activity.^[2] As a result, the production of fructose 2,6-bisphosphate increases, ultimately leading to an upregulation of glycolysis.^[3]

Although previously thought of mainly as an intermediary in the pentose phosphate pathway, recent research reported that the sugar also has a role in gene expression, mainly by promoting the ChREBP transcription factor in the well-fed state.^{[4] [5]} However, more recent study showed that D-glucose-6-phosphate, rather than D-xylulose-5-phosphate, is essential for the activation of ChREBP in response to glucose.^[6]

Notes and References

1. 6 . Stincone A, Prigione A, Cramer T, Wamelink MM, Campbell K, Cheung E, Olin-Sandoval V, Grüning NM, Krüger A, Tauqeer Alam M, Keller MA, Breitenbach M, Brindle KM, Rabinowitz JD, Ralser M . August 2015 . The return of metabolism: biochemistry and physiology of the pentose phosphate pathway . Biological Reviews of the Cambridge Philosophical Society . 90 . 3 . 927–963 . 10.1111/brv.12140 . 4470864 . 25243985 . free.
2. Book: Nelson, David L. . Lehninger principles of biochemistry . Cox . Michael M. . Nelson . David L. . 2013 . Macmillan Higher Education . 978-1-4292-3414-6 . Lehninger . Albert L. . 6th . Basingstoke . 606.
3. Uyeda K . Short- and Long-Term Adaptation to Altered Levels of Glucose: Fifty Years of Scientific Adventure . Annual Review of Biochemistry . 90 . 1 . 31–55 . June 2021 . 34153217 . 10.1146/annurev-biochem-070820-125228 . free .
4. Kabashima T, Kawaguchi T, Wadzinski BE, Uyeda K . Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver . Proceedings of the National Academy of Sciences of the United States of America . 100 . 9 . 5107–5112 . April 2003 . 12684532 . 154306 . 10.1073/pnas.0730817100 . free . 2003PNAS..100.5107K .
5. Iizuka K, Horikawa Y . ChREBP: a glucose-activated transcription factor involved in the development of metabolic syndrome . Endocrine Journal . 55 . 4 . 617–624 . August 2008 . 18490833 . 10.1507/endocrj.k07e-110 . free .
6. Dentin R, Tomas-Cobos L, Foufelle F, Leopold J, Girard J, Postic C, Ferré P . Glucose 6-phosphate, rather than xylulose 5-phosphate, is required for the activation of ChREBP in response to glucose in the liver . Journal of Hepatology . 56 . 1 . 199–209 . January 2012 . 21835137 . 10.1016/j.jhep.2011.07.019 .