D-Psicose inhibits the growth of L1 stage Caenorhabditis elegans: A possible inhibition mechanism
Toru Yamasaki
Department of Applied Biological Science, Kagawa University, Miki-Ikenobe,
Kagawa 761-0795
Japan
Abstract:
It has been reported that, among D- and L-ketohexoses (psicose, sorbose, fructose, and tagatose),D-psicose specifically inhibited the growth of L1 stage Caenorhabditiselegans.[1] Of sugars, involved in the pentose phosphate pathway, only D-ribose reversed the inhibition by D-psicose in a competitive manner.[2] The cyclic forms of each ketohexose are much more abundant in aqueous solution than the open-chain form.[3] It has been proposed that cyclic D-ribose 5-phosphate is initially docked in ribose-5-phosphate isomerase (Rpi) from Mycobacterium tuberculosis, and transformed to the open-chain form, leading to the isomerization to D-ribulose 5-phosphate.[4] C. elegans has a gene called rpia-1 which encodes a putative Rpi.[WBGene00015101] Cyclic D-psicose resembles in structure cyclic D-ribose. Therefore, cyclic D-psicose or its phosphate is very likely to be reversibly bound in Rpi to act as an enzyme-inhibitor.
Thus, the antimetabolite mode of action appears to be a block against the biosynthesis of nucleic acids, resulting in a cessation of cell division.
[1]M Sato, H Kurose, T Yamasaki, K Izumori (2008) J Nat Med 62:244-246.
[2]M Sato, N Yokoi, H Kurose, T Yamasaki (2009) Biol Pharm Bull 32:950-952.
[3]J Pierce, AS Serianni, R Barker (1985) J Am Chem Soc 107: 2448-2456.
[4]AK Roos, E Burgos, DJ Ericsson, L Salmon, SL Mowbray (2005) J Biol Chem 280:6416-6422.
